Adverse Events Associated with Lutetium-177-PSMA-617 (Pluvicto®) in Advanced Prostate Cancer: Insights from the FDA's Adverse Event Reporting System (FAERS)

Adverse Events Associated with Lutetium-177-PSMA-617 (Pluvicto®) in Advanced Prostate Cancer: Insights from the FDA's Adverse Event Reporting System (FAERS) | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Adverse Events Associated with Lutetium-177-PSMA-617 (Pluvicto®) in Advanced Prostate Cancer: Insights from the FDA's Adverse Event Reporting System (FAERS) Yongchen Jin, Yishan Zhang, Mingshuai Wang, Xiaoxuan Bai, Hao Ping, and 1 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6084374/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 30 Sep, 2025 Read the published version in BMC Cancer → Version 1 posted 14 You are reading this latest preprint version Abstract Objective Pluvicto® (Lutetium-177–PSMA-617) was the world's first radiolabeled drug for the treatment of metastatic castration-resistant prostate cancer that was positive for prostate-specific membrane antigen with limited global use to date. Our study aimed to conduct a thorough analysis based on the adverse event reporting system FAERS of the Food and Drug Administration (FDA), providing insights for its future clinical application. Methods The adverse event reports suspected primarily of Pluvicto® from April 1, 2022 to December 31, 2024 were retrieved from the FAERS system to conduct a disproportionality test. The characteristics of these reports were analyzed including demographic features, time of adverse event occurrence, and features of adverse events. Adverse events (AEs) were classified by System Organ Classes (SOCs) and preferred terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA®). The disproportionality of results was analyzed by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS). Results A total of 7654 adverse event reports suspected primarily of Pluvicto® were submitted to the database, showing a monthly increasing trend in report numbers. 649 Preferred Terms (PTs) were identified, and after screening, from which 33 significant PT signals were identified by the 4 algorithms, involving 10 SOCs after classification. Additionally, our study revealed thrombotic microangiopathy (TMA) as an adverse event not previously documented in the label. Conclusions The study confirmed the majority of significant AE signals that have been listed in the prescribing information or reported in previous studies. It was recommended that intensified laboratory monitoring and screening of clinical parameters, baseline hepatic function and potential infestation risks during initial treatment phases. Pluvicto® Lutetium-177–PSMA-617 lutetium (177Lu) vipivotide tetraxetan FAERS Adverse event Data mining Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 1. Introduction Prostate cancer is the fourth most common cancer globally and the second most common cancer in male,( 1 ) the 5-year survival rate is approximately 100% for prostate cancer patients, but it decrease to currently less than 31% for patients with distant metastases.( 2 , 3 ) Almost all patients with metastatic prostate cancer initially respond to androgen deprivation therapy, including the recent FDA-approved androgen receptor antagonists such as enzalutamide and CYP17A1 inhibitor abiraterone, both significantly improving overall survival.( 4 – 9 ) However, the development of castration-resistant prostate cancer is the leading cause of death in prostate cancer patients, most deaths related to prostate cancer are due to advanced disease, resulting from a combination of lymphatic, hematogenous, locally contiguous spread, or a combination of these mentioned above.( 10 ) Prostate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed in prostate cancer cells. ( 11 , 12 ) Its high expression in prostate cancer, limited expression in normal tissues, and association with androgen independence, metastasis, and disease progression make PSMA a promising target for diagnostic imaging and targeted therapy in metastatic prostate cancer. ( 13 ) Pluvicto® was the world's first radiolabeled drug for the treatment of metastatic castration-resistant prostate cancer that was positive for prostate-specific membrane antigen, and it was approved by the US FDA in March 2022. ( 2 , 14 , 15 ) Pluvicto® can bind to prostate cancer cells expressing prostate-specific membrane antigen and induce DNA damage through the radiation released by 177Lu, thereby killing tumor cells. Since the radiation emitted by Pluvicto® only acts over short distances, it can effectively mitigate damage to surrounding healthy cells, offering significant spatial advantages for tumor treatment. ( 13 , 16 ) As a novel radiopharmaceutical, there is relatively limited clinical experience with Pluvicto®. So, monitoring the real-world clinical safety of radiopharmaceuticals represented by Pluvicto® is of great significance. For these reasons abo, our study aims to evaluate and analyze the AEs of Pluvicto® based on the US FDA AE Reporting System (FAERS), providing evidence for the clinical monitoring of radiopharmaceuticals and stimulating the interest of this topic for further attention. 2. Data and Method 2.1 Data Source The original data used for data mining was collected from the FAERS database downloaded from the official website of the US FDA. Based on the market release date of [177Lu]Lu-PSMA-617, we queried the FAERS database and extracted all AEs (AEs) records that occurred between April 1, 2022, and December 31, 2024. All records contained demographic information of patients, possibly drugs, possibly AEs, outcomes of AE, and the occurrence time of AEs. As a public spontaneous reporting database, AE records can be submitted by healthcare professionals such as physicians, pharmacists, other healthcare professionals, and consumers(Fig. 1 ). 2.2 Data Processing The reports of monotherapy with [177Lu]Lu-PSMA-617 were analyzed, and the [177Lu]Lu-PSMA-617 was the primary suspected drug. The data cleaning rule first removed duplicates according to the FDA-recommended method. Using the generic name "177Lu-vipivotide tetraxetan", "Vipivotide tetraxetan Lu-177", "LUTETIUM (177LU) PSMA-617", "PSMA-617 Lu-177" and the brand name "Pluvicto®" as search terms, reports with [177Lu]Lu-PSMA-617 as the primary suspected drug. Duplicate reports were identified and removed based on the report information according to the deduplication process previously described.( 17 ) For ADR names in the reports, standardized encoding was done using Preferred Terms (PT) from the Medical Dictionary for Regulatory Activities (MedDRA).( 18 ) 2.3 Signal Detection Method In this study, AE signal detection utilized the Reporting Odds Ratio (ROR) method and the Proportional Reporting Ratio (PRR) method (signal detection was performed using the lower confidence interval of PRR) in the disproportionality analysis. The algorithm was based on the four-grid table of the disproportionality algorithm (Table 1 ), where 'a' represents the number of cases of the target drug-target AE, 'b' represents the number of cases of other AEs of the target drug, 'c' represents the number of cases of the target AE of other drugs, and 'd' represents the number of cases of other AEs of other drugs. Table 1 The Four-grid Table of the Disproportionality algorithm With an AE of interest Without an AE of interest Total Pluvicto® a b a + b Other drugs c d c + d Total a + c b + d N = a + b + c + d 2.4 Signal Analysis Signal detection was performed using the Reporting Odds Ratio (ROR),( 19 ) Proportional Reporting Ratio (PRR),( 20 ) Bayesian Confidence Propagation Neural Network (BCPNN),( 21 ) and Multi-item Gamma Poisson Shrinker (MGPS) methods. To reduce the potential risk of lossing target data, the signal judgment threshold adopts criteria where 'a' ≥ 3, lower limit of ROR 95% CI > 1, PRR ≥ 2, χ2 ≥ 4, IC-2SD > 0, and EBGM05 > 1.( 22 ) In this study, the ROR, MHRA, BCPNN, and MGPS combination detection results showed significant disproportionality and were considered to be present if lower limit of ROR 95% CI > 1, PRR ≥ 2, χ2 ≥ 4, IC-2SD > 0, EBGM05 > 2, and the number of cases > 3. Analysis was conducted for patients included in the analysis and who used the target drug, with statistical descriptions made for the patient. If a patient experienced multiple AEs simultaneously, it was counted only once. Analysis content included indicators such as gender, age, reporter, reporting country, reporting year, outcome, and the difference between the start date of AEs and the date of medication. 3. Results After data selection, a total of 4054016 AE reports were collected from April 1, 2022 to December 31, 2024. 7654 AE reports were identified where [177Lu]Lu-PSMA-617 was the primary suspected drug. Excluding 6773 reports without gender annotations, there were 874 reports for male patients and 7 reports for female patients(Table 2 ). Analysis of the 7 female patient reports revealed that 1 report described AE, occurring on October 1, 2022, including discomfort, gingival pain, feeding disorder, stomatitis, coating in the mouth, mouth ulcer, aphthous ulcer, and noninfective gingivitis, which were primarily diagnosed gastrointestinal disorders, but the diagnosis was unclear, indicating a potential recording error. The remaining reports did not specify corresponding diagnoses or AEs, making the authenticity of these reports uncertain. Table 2 Characteristics of reports associated with Pluvicto® from April 1, 2022 to December 31, 2023 Characters number(%) Sex Female(n) 7( 0.1) Male(%) 874(11.4) Not Specified(%) 6773(88.5) Age (year) ≥18, <65(%) 61(0.8) ≥65, <85(%) 333(4.4) 85≤(%) 18(0.2) Not Specified(%) 7242(94.6) Weight 110 kg 32(0.42%) Not Specified 7304 (95.43%) Occupation of Reporter Health Professional(%) 7070 (92.4) Pharmacist(%) 30 (0.4) Physician(%) 554 (7.2) Reporter’s Country United States of America(%) 7402 (96.7) France(%) 96 (1.3) Canada(%) 19 (0.2) Outcome Life-Threatening(%) 16 (0.2) Hospitalization - Initial or Prolonged(%) 227 (3.0) Disability(%) 9 (0.19) Death(%) 975 (12.7) Other(%) 372 (4.9) Missing(%) 6055 (79.1) 96.7% records were reported from the United States. After excluding 7304 reports without weight information, 350 reports were analyzed, with median weight was 77.80 kg ([IQR] 70.0-96.4 kg). Excluding 6055 records without clearly reported treatment outcomes, 975 records (12.70%) AEs led to death, 9 records (0.19%) of disability, 227 records of hospitalization or prolonged hospital stay in (3.0%), and 16 records (0.2%) life-threatening situations(Table 3 ). Table 3 Top 20 PTs with the highest frequency in Pluvicto® AE signal detection PT n ROR(95%Cl) PRR(X 2 ) EBGM(EBGM05) IC(IC025) ILL-DEFINED DISORDER 3487 547.04 ( 521.69–573.61 ) 366.18 ( 822186.16 ) 237.1 ( 227.87 ) 7.89 ( 7.83 ) GENERAL PHYSICAL HEALTH DETERIORATION 2616 135.51 ( 129.33–141.99 ) 102.09 ( 227861.3 ) 88.72 ( 85.32 ) 6.47 ( 6.4 ) DEATH 945 8.28 ( 7.74–8.85 ) 7.62 ( 5441.75 ) 7.55 ( 7.14 ) 2.92 ( 2.82 ) LABORATORY TEST ABNORMAL 202 56.91 ( 49.24–65.78 ) 55.84 ( 10045.46 ) 51.62 ( 45.73 ) 5.69 ( 5.48 ) DISEASE PROGRESSION 198 4.81 ( 4.18–5.54 ) 4.74 ( 581.88 ) 4.71 ( 4.19 ) 2.24 ( 2.03 ) MALIGNANT NEOPLASM PROGRESSION 119 4.49 ( 3.74–5.38 ) 4.45 ( 316.83 ) 4.43 ( 3.8 ) 2.15 ( 1.88 ) COVID-19 110 1.45 ( 1.2–1.75 ) 1.45 ( 15.33 ) 1.45 ( 1.24 ) 0.53 ( 0.26 ) PROSTATIC SPECIFIC ANTIGEN INCREASED 97 56.62 ( 45.98–69.71 ) 56.1 ( 4844.93 ) 51.85 ( 43.56 ) 5.7 ( 5.39 ) ANAEMIA 94 2.41 ( 1.97–2.96 ) 2.4 ( 76.82 ) 2.4 ( 2.02 ) 1.26 ( 0.96 ) PLATELET COUNT DECREASED 89 4.41 ( 3.58–5.44 ) 4.38 ( 231.1 ) 4.36 ( 3.66 ) 2.12 ( 1.82 ) THROMBOCYTOPENIA 74 2.35 ( 1.87–2.96 ) 2.34 ( 56.97 ) 2.34 ( 1.93 ) 1.23 ( 0.89 ) PROSTATE CANCER 68 3.42 ( 2.7–4.35 ) 3.41 ( 115.38 ) 3.4 ( 2.78 ) 1.76 ( 1.41 ) ILLNESS 68 2.91 ( 2.29–3.7 ) 2.9 ( 84.4 ) 2.89 ( 2.37 ) 1.53 ( 1.18 ) HAEMOGLOBIN DECREASED 61 4.24 ( 3.3–5.46 ) 4.22 ( 149.31 ) 4.2 ( 3.4 ) 2.07 ( 1.7 ) FATIGUE 57 0.55 ( 0.42–0.71 ) 0.55 ( 21.37 ) 0.55 ( 0.44 ) -0.87 ( -1.25 ) MALAISE 53 1.03 ( 0.78–1.35 ) 1.03 ( 0.04 ) 1.03 ( 0.82 ) 0.04 ( -0.36 ) HORMONE-REFRACTORY PROSTATE CANCER 52 121.95 ( 90.7–163.96 ) 121.35 ( 5254.99 ) 102.89 ( 80.32 ) 6.68 ( 6.26 ) ASTHENIA 48 0.98 ( 0.74–1.3 ) 0.98 ( 0.02 ) 0.98 ( 0.77 ) -0.03 ( -0.44 ) SARS-COV-2 TEST POSITIVE 47 9.95 ( 7.46–13.29 ) 9.91 ( 371.41 ) 9.78 ( 7.69 ) 3.29 ( 2.87 ) FULL BLOOD COUNT DECREASED 36 12.22 ( 8.78–17 ) 12.18 ( 362.86 ) 11.98 ( 9.09 ) 3.58 ( 3.1 ) IC025: lower end of the 95% CI of the IC, EGBM05: lower end of the 95% CI of the EGBM, IC: information component, ROR: reporting odds ratio, X 2 : Chi-Squared Test, PTs: preferred terms, CI: confidence interval, n: number of events. A total of 295 valid patient records with valid AE reports were extracted, after excluding reports with non-standardized recording and missing information, we calculated the onset time of AEs based on the start of Pluvicto® admission and the date of AE occurrence. The shortest onset time occurred on the same day as medication admission, and the longest onset time was 552 days, with an average of 86.29 days. The median onset time was 56 days ([IQR] 25.0-125.0 days), 289(97.9%) cases of AEs appeared within the first year of treatment, with the majority of cases occurring within the first 3 months after Pluvicto® treatment (n = 190, 64.41%)(Fig. 2 A and B). 4. Discussion Prior studies have highlighted other problematic aspects of Pluvicto® such as the drug's radiopharmaceutical mechanism, clinical trials, and analysis of clinical results, few studies have concentrated on the latest real-world research.( 23 – 28 ) A collection and evaluation Based on real-world data from large database was performed for the drug vigilance of Pluvicto® when it was approved by the FDA. The purpose of the study was to analyze new and meaningful AEs, guide updates to the summary of product characteristics (SmPC), and provide recommendations and evidence for clinically rational use of the drug. According to previous clinical experience, high BMI, lack of exercise, and unhealthy lifestyle habits increase the risk of prostate cancer. Upon analyzing the demographic data, we discovered that reports containing weight information from 350 identified cases indicated a significant proportion of patients receiving Pluvicto® treatment had weights ranging from 60 to 100kg (273, 78%), Notably, 85 records with weights ≥ 90 kg (24.3%), indicating a higher incidence of AEs in this weight range, which may be correlate with the higher incidence of prostate cancer. Our study analyzed 7654 AE records in the FAERS database involving Pluvicto® as the primary suspect drug, obtaining 649 potential AEs records at PT level. Using the detection criteria of ROR, PRR, BCPNN, and MGPS, a total of 33 AEs significant signals were identified(Fig. 3 and Table 4 ). After excluded 18 AE signals that did not correlate with the drug’s radiopharmaceutical effect, 15 AEs records significant signals correlated with drug effect were obtained, including laboratory test abnormal, anaemia, platelet count decreased, illness, haemoglobin decreased, full blood count decreased, dry mouth, blood test abnormal, subdural haematoma, spinal cord compression, haemoglobin abnormal, hepatic lesion, creatinine renal clearance decreased, blood creatine increased, spinal cord infection.(Fig. 4 ). Table 4 44 Significant AE signals at the Preferred Terms level in the FAERS database PT n ROR(95%Cl) PRR(X 2 ) EBGM(EBGM05) IC(IC025) ILL-DEFINED DISORDER 3487 547.04 ( 521.69–573.61 ) 366.18 ( 822186.16 ) 237.1 ( 227.87 ) 7.89 ( 7.83 ) GENERAL PHYSICAL HEALTH DETERIORATION 2616 135.51 ( 129.33–141.99 ) 102.09 ( 227861.3 ) 88.72 ( 85.32 ) 6.47 ( 6.4 ) DEATH 945 8.28 ( 7.74–8.85 ) 7.62 ( 5441.75 ) 7.55 ( 7.14 ) 2.92 ( 2.82 ) LABORATORY TEST ABNORMAL* 202 56.91 ( 49.24–65.78 ) 55.84 ( 10045.46 ) 51.62 ( 45.73 ) 5.69 ( 5.48 ) DISEASE PROGRESSION 198 4.81 ( 4.18–5.54 ) 4.74 ( 581.88 ) 4.71 ( 4.19 ) 2.24 ( 2.03 ) MALIGNANT NEOPLASM PROGRESSION 119 4.49 ( 3.74–5.38 ) 4.45 ( 316.83 ) 4.43 ( 3.8 ) 2.15 ( 1.88 ) PROSTATIC SPECIFIC ANTIGEN INCREASED 97 56.62 ( 45.98–69.71 ) 56.1 ( 4844.93 ) 51.85 ( 43.56 ) 5.7 ( 5.39 ) ANAEMIA* 94 2.41 ( 1.97–2.96 ) 2.4 ( 76.82 ) 2.4 ( 2.02 ) 1.26 ( 0.96 ) PLATELET COUNT DECREASED* 89 4.41 ( 3.58–5.44 ) 4.38 ( 231.1 ) 4.36 ( 3.66 ) 2.12 ( 1.82 ) PROSTATE CANCER 68 3.42 ( 2.7–4.35 ) 3.41 ( 115.38 ) 3.4 ( 2.78 ) 1.76 ( 1.41 ) ILLNESS* 68 2.91 ( 2.29–3.7 ) 2.9 ( 84.4 ) 2.89 ( 2.37 ) 1.53 ( 1.18 ) HAEMOGLOBIN DECREASED* 61 4.24 ( 3.3–5.46 ) 4.22 ( 149.31 ) 4.2 ( 3.4 ) 2.07 ( 1.7 ) HORMONE-REFRACTORY PROSTATE CANCER 52 121.95 ( 90.7–163.96 ) 121.35 ( 5254.99 ) 102.89 ( 80.32 ) 6.68 ( 6.26 ) SARS-COV-2 TEST POSITIVE 47 9.95 ( 7.46–13.29 ) 9.91 ( 371.41 ) 9.78 ( 7.69 ) 3.29 ( 2.87 ) FULL BLOOD COUNT DECREASED* 36 12.22 ( 8.78–17 ) 12.18 ( 362.86 ) 11.98 ( 9.09 ) 3.58 ( 3.1 ) DRY MOUTH* 32 3.26 ( 2.3–4.62 ) 3.26 ( 49.82 ) 3.24 ( 2.43 ) 1.7 ( 1.19 ) METASTASES TO BONE 23 5.99 ( 3.97–9.03 ) 5.98 ( 94.53 ) 5.93 ( 4.21 ) 2.57 ( 1.98 ) PROSTATE CANCER METASTATIC 20 35.5 ( 22.64–55.69 ) 35.44 ( 635.73 ) 33.71 ( 23.13 ) 5.07 ( 4.43 ) BLOOD TEST ABNORMAL* 17 7.32 ( 4.54–11.81 ) 7.31 ( 91.59 ) 7.24 ( 4.85 ) 2.86 ( 2.17 ) METASTASES TO LIVER 16 4.12 ( 2.52–6.74 ) 4.11 ( 37.49 ) 4.09 ( 2.71 ) 2.03 ( 1.33 ) SUBDURAL HAEMATOMA* 9 3.89 ( 2.02–7.49 ) 3.89 ( 19.19 ) 3.87 ( 2.24 ) 1.95 ( 1.04 ) SPINAL CORD COMPRESSION* 8 14.15 ( 7.02–28.5 ) 14.14 ( 95.65 ) 13.87 ( 7.72 ) 3.79 ( 2.82 ) HAEMOGLOBIN ABNORMAL* 7 7.34 ( 3.48–15.47 ) 7.34 ( 37.9 ) 7.27 ( 3.9 ) 2.86 ( 1.83 ) CANCER PAIN 6 10.55 ( 4.71–23.64 ) 10.55 ( 51.05 ) 10.4 ( 5.3 ) 3.38 ( 2.28 ) PROSTATIC SPECIFIC ANTIGEN DECREASED 6 268.06 ( 103.99–691.03 ) 267.91 ( 1139.64 ) 191.65 ( 86.78 ) 7.58 ( 6.33 ) HEPATIC LESION* 5 5.87 ( 2.43–14.15 ) 5.86 ( 20 ) 5.82 ( 2.79 ) 2.54 ( 1.36 ) PROSTATIC SPECIFIC ANTIGEN ABNORMAL 5 20.06 ( 8.24–48.84 ) 20.05 ( 87.89 ) 19.5 ( 9.26 ) 4.29 ( 3.09 ) CREATININE RENAL CLEARANCE DECREASED* 5 5.21 ( 2.16–12.56 ) 5.21 ( 16.87 ) 5.18 ( 2.48 ) 2.37 ( 1.19 ) FAILURE TO THRIVE 5 6.89 ( 2.86–16.64 ) 6.89 ( 24.92 ) 6.83 ( 3.27 ) 2.77 ( 1.59 ) BLOOD CREATINE INCREASED* 5 6.56 ( 2.72–15.82 ) 6.55 ( 23.3 ) 6.5 ( 3.11 ) 2.7 ( 1.52 ) METASTASES TO SPINE 5 10.18 ( 4.21–24.63 ) 10.18 ( 40.77 ) 10.04 ( 4.8 ) 3.33 ( 2.14 ) SPINAL CORD INFECTION* 4 40.61 ( 14.8–111.43 ) 40.59 ( 145.64 ) 38.33 ( 16.47 ) 5.26 ( 3.93 ) NEUROENDOCRINE CARCINOMA 3 17.33 ( 5.51–54.52 ) 17.32 ( 44.98 ) 16.91 ( 6.48 ) 4.08 ( 2.61 ) IC025 lower end of the 95% CI of the IC, EGBM05 lower end of the 95% CI of the EGBM, IC information component, ROR reporting odds ratio, X 2 Chi-Squared Test, PTs preferred terms, CI confidence interval, n number of events. * AEs correlate with Pluvicto® admission Table 5 Disproportionality analysis at the SOC level in FAERS Database System Organ Class(SOC) AE Signals Proportion(%) AE(cases) Proportion(%) GENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS 51 7.8 7691 73.05 NERVOUS SYSTEM DISORDERS 51 7.8 125 1.19 RESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS 24 3.6 87 0.83 GASTROINTESTINAL DISORDERS 50 7.7 205 1.95 INFECTIONS AND INFESTATIONS 42 6.4 244 2.32 BLOOD AND LYMPHATIC SYSTEM DISORDERS 30 4.6 313 2.97 INVESTIGATIONS 99 15.2 819 7.78 EYE DISORDERS 15 2.3 22 0.21 RENAL AND URINARY DISORDERS 28 4.3 115 1.09 INJURY, POISONING AND PROCEDURAL COMPLICATIONS 39 6.0 125 1.19 VASCULAR DISORDERS 19 2.9 49 0.47 METABOLISM AND NUTRITION DISORDERS 28 4.3 94 0.89 PSYCHIATRIC DISORDERS 19 2.9 35 0.33 NEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS) 47 7.2 375 3.56 CARDIAC DISORDERS 21 3.2 58 0.55 HEPATOBILIARY DISORDERS 21 3.2 47 0.45 MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS 26 4.0 76 0.72 SKIN AND SUBCUTANEOUS TISSUE DISORDERS 16 2.4 23 0.22 ENDOCRINE DISORDERS 3 0.4 3 0.03 EAR AND LABYRINTH DISORDERS 3 0.4 4 0.04 PRODUCT ISSUES 9 1.3 10 0.09 CONGENITAL, FAMILIAL AND GENETIC DISORDERS 1 0.1 1 0.01 REPRODUCTIVE SYSTEM AND BREAST DISORDERS 4 0.6 4 0.04 SOCIAL CIRCUMSTANCES 1 0.1 1 0.01 IMMUNE SYSTEM DISORDERS 2 0.3 2 0.02 Total 649 100.00 10528 100.00 AE, Adverse Event. SOC, System Organ Class. Disproportionality analysis revealed that the most frequently reported and clinically significant signals at the System Organ Class (SOC) level comprised general disorders and administration site conditions (n = 7,691, 73.05%), investigations (n = 819, 7.78%), and neoplasms benign, malignant and unspecified (including cysts and polyps) (n = 375, 3.56%) (Fig. 5 and Table 5 ). Notably, several adverse events (AEs) within these SOC categories—including death, malignant neoplasm progression, hormone-refractory prostate cancer, asthenia, prostate cancer, and bone metastases—were absent from the Pluvicto® Summary of Product Characteristics (SmPC) and appear more likely attributable to underlying disease progression than direct pharmacological effects. Nevertheless, our analysis identified drug-related AEs (Preferred Terms: fatigue, dry mouth, anemia, pancytopenia, etc) demonstrating temporal and pharmacological plausibility with Pluvicto® administration, consistent with the U.S. Food and Drug Administration (FDA) Adveres Event Documentation. While Pluvicto®s therapeutic mechanism involves targeted delivery of ionizing radiation, causal attribution of tumor metastasis/progression to the radiopharmaceutical requires rigorous clinical-pathological correlation. Clinicians should conduct comprehensive benefit-risk assessments, ensuring radiation exposure risks remain substantially below baseline oncological risks. Several AEs were thought to be related to blood and lymphatic system disorders, particularly those involving red blood cells, hemoglobin, platelet reduction, total blood cell reduction, and bone marrow failure, all of which indicate the inhibitory effect of Pluvicto® on hematopoietic system function. In the Pluvicto® SmPC, blood and lymphatic system abnormalities include anemia, thrombocytopenia, leukopenia, neutropenia, and pancytopenia. Prior clinical trials have all demonstrated that abnormalities in the blood and lymphatic systems were common and complex AEs of Pluvicto®. Pooled clinical data(VISION phase III [NCT03511664] ( 2 ) TheraP phase II [NCT03392428] ( 29 ), LuPSMA [NCT03828838] ( 30 )) demonstrate dose-dependent hematologic toxicity profiles. The VISION study(phase III [NCT03511664])( 2 ) was a randomized phase III clinical trial that compared the efficacy of Pluvicto® combined with Best Standard of Care (BSoC) versus BSoC alone (including, but not limited to, approved hormonal therapies, bisphosphonates, radiation therapy, Denosumab, and any dose of glucocorticoids). Patients who received Pluvicto® treatment demonstrated significantly superior outcomes in imaging-based progression-free survival and overall survival compared to the control group, underscoring its treatment efficacy. However, Grade ≥ 3 hematologic ADRs were substantially more prevalent with Pluvicto® versus controls: anemia (12.9% vs 3.8%), thrombocytopenia (7.9% vs 0.5%), lymphocytopenia (7.8% vs 0%), neutropenia (4.5% vs 0.2%), with two fatal pancytopenia events (1.1%). These results were consistent with the findings of Michael S Hofman et al ( 29 ) in the Phase II TheraP trial. In the TheraP trial, Michael et al. compared Pluvicto® to cabazitaxel, a second-generation semisynthetic microtubule inhibitor that stabilizes microtubules and induces tumor cell death. In their study, Pluvicto® was more effective relative to cabazitaxel in patients with metastatic castration-resistant prostate cancer. Regarding AEs, it was noteworthy that the incidence of severe adverse events (SAEs, GRADE 3/4) with Pluvicto® was lower than with cabazitaxel, with 32 cases (33%) of SAEs among 98 males treated with Pluvicto® and 45 cases (53%) among 85 males treated with cabazitaxel. Grade 3/4 neutropenia was less common with Pluvicto® (4% vs. 13%), but Grade 3/4 thrombocytopenia induced by Pluvicto® was more common than cabazitaxel (11% vs. 0%). The mechanism of bone marrow suppression and hematologic and lymphatic system abnormalities caused by Pluvicto® may involve multiple contributing factors. Similar AEs were also reported in the LuPSMA trial,( 30 ) with thrombocytopenia being the most common AE, aside from mild discomfort symptoms (such as dry mouth and dry eyes). This study found that the reporting frequency of thrombocytopenia in a large sample database was higher than that of other symptoms, such as dry mouth, nausea, and fatigue, suggesting that thrombocytopenia in some patients may be attributed to bone marrow infiltration by prostate cancer metastasis rather than to Pluvicto® admission. Michael Hofmann et al ( 30 ) performed bone marrow biopsies on 3 patients in the LuPSMA trial, revealing extensive prostate cancer infiltration in the bone marrow. Pluvicto® is a radio-labeled small molecule with high affinity for the enzymatic active site of PSMA, enabling highly targeted beta radiation delivery to prostate cancer cells. The presence of prostate cancer infiltration in the bone marrow implies blurred boundaries between normal bone marrow and tumors, which leads to radiation exposure of both normal bone marrow tissue and tumors by Pluvicto®, resulting in hematologic suppression and bone marrow damage. Violet et.al ( 15 ) also reported leukoerythroblastic pancytopenia as the primary dose-limiting toxicity (DLT) in patients with diffuse marrow infiltration, manifesting as leuko-erythroblastic pancytopenia, sufficient to cause cessation of Pluvicto® treatment. Existing clinical trial results indicated that most patients received chemotherapy or hormone therapy before Pluvicto® treatment, suggesting that prior treatments may have reduced patients' bone marrow reserves, and exacerbated hematologic lymphatic system damage after Pluvicto® admission. Hematologic and lymphatic system AEs were also correlated with other more severe AEs, thrombocytopenia and marrow failure may increase the incidence of subdural hematoma and gingival bleeding, while pancytopenia and marrow failure lead to decreased immune function, increasing the risk of infection. Our study identified multiple serious adverse events (SAEs) within hematolymphatic system disorder, including anemia (2.41, 95%CI 1.97–2.96), pancytopenia (2.27, 95%CI 1.63–3.16), myelosuppression (0.96, 95%CI 0.62–1.47), bone marrow failure (1.88, 95%CI 0.7-5.00), disseminated intravascular coagulation (DIC) (1.12, 95%CI 0.36–3.46), and thrombotic microangiopathy (TMA) (0.87, 95%CI 0.28–2.71). These findings necessitate risk-adapted therapeutic algorithms: Pre-treatment bone marrow reserve quantification via hybrid imaging (¹⁸F-FDG PET/CT) and metastatic burden stratification using circulating tumor DNA (ctDNA) analysis should be mandated to optimize therapeutic index during clinical decision-making. To analyze the temporal relationship between adverse events (AEs) and onset time, we systematically evaluated AEs across different time periods at the System Organ Class (SOC) level. For SOCs with ≥ 5 AEs, Pearson's χ² test was applied; otherwise, Fisher's exact test was employed to enhance analytical precision (Fig. 6 ). Notably, the "Investigations" SOC demonstrated significant signals across all time intervals except at 30 and 60 days. The early event proportion for this SOC exceeded 50% from day 90 onward, indicating that over half of AEs categorized under "Investigations" (e.g., Laboratory test abnormal [n = 202], Prostatic specific antigen increased [n = 97], Platelet count decreased [n = 89]) occurred within the first three months post-Pluvicto® administration, underscoring the necessity for intensified laboratory monitoring of clinical test results during initial treatment phases. Our analysis identified previously underrecognized infection-related AEs. The Infections and Infestations SOC demonstrated positive signals at 15, 30, 150, and 180 days, with 63.1% of Preferred Terms (PTs) concentrated in three categories: COVID-19 (n = 110, ROR 1.95, 95% CI 1.32–2.88), pneumonia (n = 27, ROR 3.45, 95% CI 2.11–5.63), and urinary tract infection (n = 17, ROR 2.78, 95% CI 1.65–4.69). These findings advocate for prophylactic measures against pathogen exposure during early-phase treatment (≤ 30 days) and late-phase follow-up (150–180 days), particularly targeting respiratory and genitourinary systems. Interestingly, Hepatobiliary Disorders SOC exhibited significant signals during the first treatment cycle (6 weeks), with early event proportions consistently exceeding 50%, suggesting first-dose predisposition. While only hepatic lesion (n = 5, ROR 5.87, 95% CI 2.43–14.15) met all four signal detection algorithms, this SOC encompassed Grade 3/4 adveres events (hepatic failure [n = 5], hepatic cytolysis[n = 2], hepatotoxicity [n = 2]), necessitating baseline hepatic function screening to mitigate severe adverse outcomes. Other SOCs (Musculoskeletal/Connective Tissue Disorders, Cardiac Disorders, Nervous System Disorders, Gastrointestinal Disorders) also exhibited limited case numbers and low early event frequencies. These preliminary observations require validation through larger cohort studies to minimize potential type II errors. Furthermore, the LuPSMA trial demonstrated that Pluvicto® appeared to induce rapid and clinically meaningful pain relief, with 27 patients (37%) achieving symptomatic improvement following the first treatment cycle, surpassing the 9% pain relief observed in cabazitaxel-treated patients from the TROPIC trial.( 30 , 33 ) In metastatic castration-resistant prostate cancer (mCRPC), pain pathogenesis primarily stems from osteoblastic bone metastases, lumbosacral infiltration, and neural compression, while also correlating with reduced overall survival. Skeletal involvement remains highly prevalent in this population, frequently causing debilitating pain, symptomatic skeletal events (SSEs), functional impairment, quality of life deterioration, and mortality. Our study corroborates these findings, within the Musculoskeletal and Connective Tissue Disorders System Organ Class (SOC), Preferred Terms (PTs) associated with somatic pain represented a minimal proportion of reports (n = 45, 0.43%). Notably, none of these pain-related PTs demonstrated significant safety signals when analyzed through our four distinct pharmacovigilance algorithms (including ROR, PRR, MGPS and BCPNN). Fizazi et al demonstrated that symptomatic skeletal events (SSEs) significantly exacerbated pain severity and compromised quality of life metrics in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases.( 33 ) Comparative efficacy data from the TheraP trial revealed a higher incidence of Grade 3/4 pain with Pluvicto® versus cabazitaxel (11% [14/127] vs 5% [6/126]).( 29 ) In the predefined subgroup of 178 patients with baseline Present Pain Intensity (PPI) scores ≥ 2 (Pluvicto®: n = 80; cabazitaxel: n = 98), pain responses were observed in 60% (48/80) versus 43% (42/98) respectively. In the CARD study, cabazitaxel plus abiraterone or enzalutamide delayed the time to the first symptomatic skeletal event in patients with metastatic castration-resistant prostate cancer and improved pain response but did not delay the time to FACT-P score deterioration. In the COMET-1 and COMET-2 studies, cabozantinib delayed the time to the first symptomatic skeletal event in patients with metastatic castration-resistant prostate cancer when compared to prednisone. ( 33 ) Notably, the VISION trial reported Pluvicto® delayed median time to first SSE or death compared to standard care (11.5 vs 6.8 months; HR = 0.50, 95% CI 0.40–0.62).( 2 ) Furthermore, Pluvicto® reduced incidence of spinal cord compression - the most debilitating SSE subtype (3.7% vs 6.5%), supporting optimized analgesic strategies during treatment. Regarding AEs associated with troublesome symptoms, this study demonstrated that although these symptoms were frequently reported and substantially impacted patients' subjective experiences during Pluvicto® (lutetium Lu 177 vipivotide tetraxetan) therapy, only xerostomia (n = 29) fulfilled the criteria across all four analytical algorithms. Other burdensome symptoms - including fatigue (n = 54), nausea (n = 35), discomfort (n = 35), asthenia (n = 32), decreased appetite (n = 24), vomiting (n = 21), diarrhea (n = 13), and constipation (n = 10) - predominantly met the criteria specific to the Multi-item Gamma Poisson Shrinker (MGPS) algorithm. In the TheraP trial, Hofman et al. ( 29 ) compared Pluvicto® with cabazitaxel and observed lower incidence rates of treatment-emergent troublesome symptoms with Pluvicto®, including diarrhea (31% vs 55%), urinary symptoms (38% vs 62%), dizziness/vertigo (38% vs 53%), dysgeusia (54% vs 69%), alopecia (10% vs 42%), rash (14% vs 32%), and palmar-plantar erythrodysesthesia (35% vs 43%). The AE profiles reported in the VISION study and LuPSMA trial aligned with these findings, though incidence rates substantially exceeded those in the FDA Adverse Event Reporting System (FAERS) database. This discrepancy may stem from differential reporting practices, as some trials potentially categorized certain manifestations as non-specific disorders rather than troublesome symptoms.( 2 , 30 ) Due to the highly targeted and short-range β particle radiation characteristics of Pluvicto® (lutetium Lu 177 vipivotide tetraxetan), physiological sites expressing prostate-specific membrane antigen (PSMA), such as salivary and lacrimal glands, may also be affected, thereby explaining characteristic AEs (e.g., dry mouth and dry eyes). While most troublesome symptoms remain self-limited, supportive measures including artificial tears, anti-diarrheals, and antiemetics are recommended for symptomatic management. 5. Conclusion Through our comprehensive pharmacovigilance analysis of the FAERS database, we underscores the the risk profile and significant AE signals with Pluvicto® (lutetium Lu 177 vipivotide tetraxetan) as the primary suspect drug. Our study confirms dose-dependent hematologic toxicity, with Grade ≥ 3 anemia (12.9%), thrombocytopenia (7.9%), and lymphocytopenia (7.8%) prominently observed in pooled clinical trial data (VISION, TheraP, LuPSMA), consistent with prior reports. Notably, thrombocytopenia emerged as a recurrent adverse event (AE), potentially attributable to direct radiation-induced bone marrow suppression and preexisting metastatic infiltration, as evidenced by histopathologic confirmation of marrow involvement in subset analyses. Temporal SOC analysis revealed abnormal laboratory investigations and hepatobiliary disorders predominantly manifested within initial treatment cycles (≤ 90 days), necessitating vigilant laboratory monitoring during early phases. Infections and infestations, particularly COVID-19 (ROR 1.95), pneumonia (ROR 3.45), and urinary tract infections (ROR 2.78), exhibited biphasic susceptibility peaks (≤ 30 and 150–180 days), advocating targeted prophylactic measures. While troublesome symptoms (dry mouth, fatigue, nausea, etc) were frequently reported, only xerostomia met all signal detection criteria, reflecting PSMA-targeted radiation effects on salivary/lacrimal glands. However, limitations including ascertainment bias and confounding by disease progression necessitate validation through larger cohort studies. Future research should prioritize mechanistic studies to disentangle drug-related hemato-lymphologic toxicity, hepatobiliary disorders and potential infestation risks, while preserving Pluvicto®’s survival benefits in advanced prostate cancer patients, optimize risk-adapted therapeutic strategies for high-risk population. Abbreviations AE Adverse Event FAERS FDA Adverse Event Reporting System FDA Food and Drug Administration PSMA Prostate-Specific Membrane Antigen ROR Reporting Odds Ratio PRR Proportional Reporting Ratio BCPNN Bayesian Confidence Propagation Neural Network MGPS Multi-item Gamma Poisson Shrinker MedDRA Medical Dictionary for Regulatory Activities SOC System Organ Class PT Preferred Term TMA Thrombotic Microangiopathy SmPC Summary of Product Characteristics SAE Severe Adverse Event BMI Body Mass Index ADR Adverse Drug Reaction CI Confidence Interval IQR Interquartile Range EBGM Empirical Bayes Geometric Mean IC Information Component Declarations Ethics approval and consent to participate Institutional review board approval was waived for this study because FAERS is a public anonymized database. Consent for publication Data that support the findings of this study is obtained from the FDA Adverse Event Reporting System (FAERS) database that was provided by the FDA. No individual patient consent was required for the publication of this study. Availability of data and materials The data that support the findings of this study are available from the FDA Adverse Event Reporting System (FAERS) database (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-adverse-event-reporting-system-faers-database). No datasets were generated during the current study. Competing interest The authors declare that they have no competing interest. Funding This study was supported by the National Key R&D Program of China (Grant No. 2023YFC2507000), the National Natural Science Foundation of China (Grant No. 82072833 and No. 82272864 to Hao Ping), Capital’s Funds for Health Improvement and Research (Grant No. 2024-2-2059). Authors’ contributions Y. J. and Y.Z. had full access to all the data in the study and took responsibility for the integrity of the data analysis. Concept design: Y.J., M.W., Y.Z.. Acquisition, analysis, and interpretation of data: All authors. Critical revision of the manuscript: All authors. Administrative, technical, or material support: N.X., H.P.. Supervision: N.X., H.P.. *Y.J., Y.Z. and M.W. have made equal contributions to the development and preparation of this manuscript. Acknowledgments This study was performed using the FDA Adverse Event Reporting System (FAERS) database that was provided by the FDA. The information, results, or interpretation of the current study do not represent any opinion of the FDA. References Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17–48. Sartor O, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385:1091–103. Patrikidou A, et al. Who dies from prostate cancer? Prostate Cancer Prostatic Dis. 2014;17:348–52. Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Stat 2022 CA: Cancer J Clin 72, (2022). Scher HI, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97. Ryan CJ, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152–60. Fizazi K, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983–92. Attard G, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet (London England). 2022;399:447–60. Beer TM, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424–33. Zhai Z, et al. Incidence and disease burden of prostate cancer from 1990 to 2017: Results from the Global Burden of Disease Study 2017. Cancer. 2020;126:1969–78. Bostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer. 1998;82:2256–61. Minner S, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 2011;71:281–8. Rowe SP, Gorin MA, Pomper MG. Imaging of Prostate-Specific Membrane Antigen with Small-Molecule PET Radiotracers: From the Bench to Advanced Clinical Applications. Annu Rev Med. 2019;70:461–77. Afshar-Oromieh A, et al. The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions. J Nuclear Medicine: Official Publication Soc Nuclear Med. 2015;56:1697–705. Violet J, et al. Dosimetry of 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: Correlations Between Pretherapeutic Imaging and Whole-Body Tumor Dosimetry with Treatment Outcomes. J Nuclear Medicine: Official Publication Soc Nuclear Med. 2019;60:517–23. Hennrich U, Eder M. [177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Pharmaceuticals (Basel Switzerland) 15, (2022). Chen C, et al. Cardiotoxicity Induced by Immune Checkpoint Inhibitors: A Pharmacovigilance Study From 2014 to 2019 Based on FAERS. Front Pharmacol. 2021;12:616505. Brown EG. Using MedDRA: implications for risk management. Drug Saf. 2004;27:591–602. Rothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004;13:519–23. Evans SJ, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf. 2001;10:483–6. Bate A, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol. 1998;54:315–21. van Puijenbroek EP et al. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf 11, (2002). Groener D et al. Impact of [177Lu]Lu-PSMA-617 Radioligand Therapy on Reference Organ Uptake Assessed by [68Ga]Ga-PSMA-11-PET/CT. Cancers 15, (2023). Mehrens D et al. Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. J Natl Compr Cancer Network: JNCCN 21, (2023). Patell K, et al. Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review. Expert Rev Anticancer Ther. 2023;23:731–44. Ramnaraign B, Sartor O. PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials. Oncologist. 2023;28:392–401. Schäfer H, et al. Extensive 177Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy-like Picture. Eur Urol. 2023;83:385–90. Giunta EF, et al. 177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers. Cancer Treat Rev. 2024;125:102699. Hofman MS, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet (London England). 2021;397:797–804. Hofman MS, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33. Lawton CA, et al. Late renal dysfunction in adult survivors of bone marrow transplantation. Cancer. 1991;67:2795–800. Saha BK, Saha A, Chong W, Beegle S. A Fatal Case of Thrombotic Microangiopathy Without Schistocytosis and Absent Biochemical Markers of Hemolysis. Am J Med Sci. 2020;359:296–302. Sonpavde GP, et al. Cabozantinib for Progressive Metastatic Castration-resistant Prostate Cancer Following Docetaxel: Combined Analysis of Two Phase 3 Trials. Eur Urol Oncol. 2020;3:540–3. Additional Declarations No competing interests reported. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6084374","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":433960948,"identity":"f8d2dfd4-1cd5-4644-b8f4-d7011a05ecce","order_by":0,"name":"Yongchen Jin","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yongchen","middleName":"","lastName":"Jin","suffix":""},{"id":433960949,"identity":"ac22e517-9d68-481c-a304-201028c53c19","order_by":1,"name":"Yishan Zhang","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Yishan","middleName":"","lastName":"Zhang","suffix":""},{"id":433960950,"identity":"77ec9dc4-0125-4bfa-ab2a-5b0708524b0a","order_by":2,"name":"Mingshuai Wang","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Mingshuai","middleName":"","lastName":"Wang","suffix":""},{"id":433960952,"identity":"3d644737-622d-46b4-bea7-7ac9ffe66573","order_by":3,"name":"Xiaoxuan Bai","email":"","orcid":"","institution":"Capital Medical University","correspondingAuthor":false,"prefix":"","firstName":"Xiaoxuan","middleName":"","lastName":"Bai","suffix":""},{"id":433960953,"identity":"2e51c847-52e3-4ea1-bed8-cf6de7a72ec6","order_by":4,"name":"Hao Ping","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAx0lEQVRIiWNgGAWjYDCCAzDE3tj44ANpWngONxvOIFYLhJRIb5PmIEYH3+2zBw8X/Lojzy/5sEGagcFOTreBgBbJc3kJh2f2PTOcOTuxwbiAIdnY7AABLQZneAwO8/YcZtxwO7EheQbDgcRtxGqx33DzYMNhHqK18Pw4nLjhBmNjM1FaJM/wJRzmbTicPLMnsZlxhgERfuE7w3v4M8+fw7b97Mef//hQYSdHUAswChkYGNvg7iSoHKqF4Q9RKkfBKBgFo2CkAgCUMU5fzcvhMgAAAABJRU5ErkJggg==","orcid":"","institution":"Capital Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hao","middleName":"","lastName":"Ping","suffix":""},{"id":433960955,"identity":"fa9d6640-3bd8-4355-ba08-c3d881bd58c2","order_by":5,"name":"Nianzeng Xing","email":"","orcid":"","institution":"National Cancer Center, Chinese Academy of Medical Sciences and Peking Union Medical College","correspondingAuthor":false,"prefix":"","firstName":"Nianzeng","middleName":"","lastName":"Xing","suffix":""}],"badges":[],"createdAt":"2025-02-22 08:53:21","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6084374/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6084374/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12885-025-14846-x","type":"published","date":"2025-09-30T15:58:11+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":79325586,"identity":"17e77f5a-b88c-43d3-9800-4860091719ae","added_by":"auto","created_at":"2025-03-27 05:28:55","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":102151,"visible":true,"origin":"","legend":"\u003cp\u003eScheme of the study with the including/excluding criteria. Publicly available FAERS data from 1 April 2022 to 31 December 2024 were filtered using this including/excluding criterion. n, case number of Pluvicto®; PS referring to the primary suspected drug.\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/a98d08c0367077fbf9cb0247.png"},{"id":79324365,"identity":"4b85649d-27b5-4ece-9e9b-58e0f24588ee","added_by":"auto","created_at":"2025-03-27 05:10:16","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":96639,"visible":true,"origin":"","legend":"\u003cp\u003eA: The adverse event onset time distribution bar chart. x-axis, time periods of onset time. y-axis, case number. B: The time-to-event of Pluvicto®-related AEs. x-axis, time-to-event counted in days. y-axis, cumulative percentage.\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/8e8381f590efeb67dd956b2d.png"},{"id":79324366,"identity":"af3676fb-2483-4914-bb06-1b2ab704cfad","added_by":"auto","created_at":"2025-03-27 05:10:16","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":60378,"visible":true,"origin":"","legend":"\u003cp\u003eVenn diagram of AEs slected by ROR(Reporting Odds Ratio), PRR(Proportional Reporting Ratio), EBGM(Multi-item Gamma Poisson Shrinker), BCPNN(Bayesian Confidence Propagation Neural Network)\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/70bbbee4198122ad5cc81742.png"},{"id":79324372,"identity":"ecbdea92-f8f7-4aea-9c89-756d8353dd1f","added_by":"auto","created_at":"2025-03-27 05:10:16","extension":"png","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":354770,"visible":true,"origin":"","legend":"\u003cp\u003eForest Plot of the Reporting odds ratios (ROR) of the 33 significant AEs related to Pluvicto® admission\u003c/p\u003e","description":"","filename":"floatimage4.png","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/a27ca2309c759295d2a39e18.png"},{"id":79324375,"identity":"899c1002-49d3-4e35-b1dd-9b3f1008177c","added_by":"auto","created_at":"2025-03-27 05:10:17","extension":"png","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":272345,"visible":true,"origin":"","legend":"\u003cp\u003eSignificant AE signals sorted by System Organ Class(SOC). x-axis, number of reported cases. y-axis, System Organ Class(SOC)\u003c/p\u003e","description":"","filename":"floatimage5.png","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/8e7934f82b3687e7f3b559dd.png"},{"id":79324370,"identity":"adb2b26c-5dda-499f-ab07-d7a30a654e3e","added_by":"auto","created_at":"2025-03-27 05:10:16","extension":"png","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":178730,"visible":true,"origin":"","legend":"\u003cp\u003eSOC time distributionanalysis. SOC, system organ class. X axis, early event proportion. Y axis, -log10(P value)\u003c/p\u003e","description":"","filename":"floatimage6.png","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/064fed4f17749cb0786a220a.png"},{"id":92884034,"identity":"84d6edda-6a92-4973-98ff-f39abe795935","added_by":"auto","created_at":"2025-10-06 16:12:16","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1849235,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6084374/v1/06abec3f-e7e7-42b1-b46f-7962b37b5b31.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Adverse Events Associated with Lutetium-177-PSMA-617 (Pluvicto®) in Advanced Prostate Cancer: Insights from the FDA's Adverse Event Reporting System (FAERS)","fulltext":[{"header":"1. Introduction","content":"\u003cp\u003eProstate cancer is the fourth most common cancer globally and the second most common cancer in male,(\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e) the 5-year survival rate is approximately 100% for prostate cancer patients, but it decrease to currently less than 31% for patients with distant metastases.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e) Almost all patients with metastatic prostate cancer initially respond to androgen deprivation therapy, including the recent FDA-approved androgen receptor antagonists such as enzalutamide and CYP17A1 inhibitor abiraterone, both significantly improving overall survival.(\u003cspan additionalcitationids=\"CR5 CR6 CR7 CR8\" citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e) However, the development of castration-resistant prostate cancer is the leading cause of death in prostate cancer patients, most deaths related to prostate cancer are due to advanced disease, resulting from a combination of lymphatic, hematogenous, locally contiguous spread, or a combination of these mentioned above.(\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eProstate-specific membrane antigen (PSMA) is a type II transmembrane glycoprotein overexpressed in prostate cancer cells. (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e, \u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e) Its high expression in prostate cancer, limited expression in normal tissues, and association with androgen independence, metastasis, and disease progression make PSMA a promising target for diagnostic imaging and targeted therapy in metastatic prostate cancer. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e) Pluvicto\u0026reg; was the world's first radiolabeled drug for the treatment of metastatic castration-resistant prostate cancer that was positive for prostate-specific membrane antigen, and it was approved by the US FDA in March 2022. (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) Pluvicto\u0026reg; can bind to prostate cancer cells expressing prostate-specific membrane antigen and induce DNA damage through the radiation released by 177Lu, thereby killing tumor cells. Since the radiation emitted by Pluvicto\u0026reg; only acts over short distances, it can effectively mitigate damage to surrounding healthy cells, offering significant spatial advantages for tumor treatment. (\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e) As a novel radiopharmaceutical, there is relatively limited clinical experience with Pluvicto\u0026reg;. So, monitoring the real-world clinical safety of radiopharmaceuticals represented by Pluvicto\u0026reg; is of great significance. For these reasons abo, our study aims to evaluate and analyze the AEs of Pluvicto\u0026reg; based on the US FDA AE Reporting System (FAERS), providing evidence for the clinical monitoring of radiopharmaceuticals and stimulating the interest of this topic for further attention.\u003c/p\u003e"},{"header":"2. Data and Method","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Data Source\u003c/h2\u003e \u003cp\u003eThe original data used for data mining was collected from the FAERS database downloaded from the official website of the US FDA. Based on the market release date of [177Lu]Lu-PSMA-617, we queried the FAERS database and extracted all AEs (AEs) records that occurred between April 1, 2022, and December 31, 2024. All records contained demographic information of patients, possibly drugs, possibly AEs, outcomes of AE, and the occurrence time of AEs. As a public spontaneous reporting database, AE records can be submitted by healthcare professionals such as physicians, pharmacists, other healthcare professionals, and consumers(Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Data Processing\u003c/h2\u003e \u003cp\u003eThe reports of monotherapy with [177Lu]Lu-PSMA-617 were analyzed, and the [177Lu]Lu-PSMA-617 was the primary suspected drug. The data cleaning rule first removed duplicates according to the FDA-recommended method. Using the generic name \"177Lu-vipivotide tetraxetan\", \"Vipivotide tetraxetan Lu-177\", \"LUTETIUM (177LU) PSMA-617\", \"PSMA-617 Lu-177\" and the brand name \"Pluvicto\u0026reg;\" as search terms, reports with [177Lu]Lu-PSMA-617 as the primary suspected drug. Duplicate reports were identified and removed based on the report information according to the deduplication process previously described.(\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e) For ADR names in the reports, standardized encoding was done using Preferred Terms (PT) from the Medical Dictionary for Regulatory Activities (MedDRA).(\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e)\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Signal Detection Method\u003c/h2\u003e \u003cp\u003eIn this study, AE signal detection utilized the Reporting Odds Ratio (ROR) method and the Proportional Reporting Ratio (PRR) method (signal detection was performed using the lower confidence interval of PRR) in the disproportionality analysis. The algorithm was based on the four-grid table of the disproportionality algorithm (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), where 'a' represents the number of cases of the target drug-target AE, 'b' represents the number of cases of other AEs of the target drug, 'c' represents the number of cases of the target AE of other drugs, and 'd' represents the number of cases of other AEs of other drugs.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eThe Four-grid Table of the Disproportionality algorithm\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"4\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eWith an AE of interest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eWithout an AE of interest\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePluvicto\u0026reg;\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;b\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther drugs\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ec\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003ed\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003ec\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003ea\u0026thinsp;+\u0026thinsp;c\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eb\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003eN\u0026thinsp;=\u0026thinsp;a\u0026thinsp;+\u0026thinsp;b\u0026thinsp;+\u0026thinsp;c\u0026thinsp;+\u0026thinsp;d\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Signal Analysis\u003c/h2\u003e \u003cp\u003eSignal detection was performed using the Reporting Odds Ratio (ROR),(\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e) Proportional Reporting Ratio (PRR),(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e) Bayesian Confidence Propagation Neural Network (BCPNN),(\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e) and Multi-item Gamma Poisson Shrinker (MGPS) methods. To reduce the potential risk of lossing target data, the signal judgment threshold adopts criteria where 'a' \u0026ge; 3, lower limit of ROR 95% CI\u0026thinsp;\u0026gt;\u0026thinsp;1, PRR\u0026thinsp;\u0026ge;\u0026thinsp;2, χ2\u0026thinsp;\u0026ge;\u0026thinsp;4, IC-2SD\u0026thinsp;\u0026gt;\u0026thinsp;0, and EBGM05\u0026thinsp;\u0026gt;\u0026thinsp;1.(\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e) In this study, the ROR, MHRA, BCPNN, and MGPS combination detection results showed significant disproportionality and were considered to be present if lower limit of ROR 95% CI\u0026thinsp;\u0026gt;\u0026thinsp;1, PRR\u0026thinsp;\u0026ge;\u0026thinsp;2, χ2\u0026thinsp;\u0026ge;\u0026thinsp;4, IC-2SD\u0026thinsp;\u0026gt;\u0026thinsp;0, EBGM05\u0026thinsp;\u0026gt;\u0026thinsp;2, and the number of cases\u0026thinsp;\u0026gt;\u0026thinsp;3. Analysis was conducted for patients included in the analysis and who used the target drug, with statistical descriptions made for the patient. If a patient experienced multiple AEs simultaneously, it was counted only once. Analysis content included indicators such as gender, age, reporter, reporting country, reporting year, outcome, and the difference between the start date of AEs and the date of medication.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cp\u003eAfter data selection, a total of 4054016 AE reports were collected from April 1, 2022 to December 31, 2024. 7654 AE reports were identified where [177Lu]Lu-PSMA-617 was the primary suspected drug. Excluding 6773 reports without gender annotations, there were 874 reports for male patients and 7 reports for female patients(Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Analysis of the 7 female patient reports revealed that 1 report described AE, occurring on October 1, 2022, including discomfort, gingival pain, feeding disorder, stomatitis, coating in the mouth, mouth ulcer, aphthous ulcer, and noninfective gingivitis, which were primarily diagnosed gastrointestinal disorders, but the diagnosis was unclear, indicating a potential recording error. The remaining reports did not specify corresponding diagnoses or AEs, making the authenticity of these reports uncertain.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eCharacteristics of reports associated with Pluvicto\u0026reg; from April 1, 2022 to December 31, 2023\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"2\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCharacters\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003enumber(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSex\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFemale(n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7( 0.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMale(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e874(11.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6773(88.5)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eAge (year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;18, \u0026lt;65(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e61(0.8)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026ge;65, \u0026lt;85(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e333(4.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e85\u0026le;(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18(0.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7242(94.6)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eWeight\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026lt;50 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e3 (0.04%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e50\u0026ndash;60 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e24(0.31%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e61\u0026ndash;70 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e73(0.95%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e71\u0026ndash;80 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e95(1.24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e81\u0026ndash;90 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e70(0.91%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e91\u0026ndash;100 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e35(0.46%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e101\u0026ndash;110 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e18(0.24%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003e\u0026gt;\u0026thinsp;110 kg\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e32(0.42%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNot Specified\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7304 (95.43%)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOccupation of Reporter\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHealth Professional(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7070 (92.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePharmacist(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e30 (0.4)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePhysician(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e554 (7.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eReporter\u0026rsquo;s Country\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eUnited States of America(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e7402 (96.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFrance(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e96 (1.3)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCanada(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e19 (0.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOutcome\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLife-Threatening(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e16 (0.2)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHospitalization - Initial or Prolonged(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e227 (3.0)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDisability(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e9 (0.19)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDeath(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e975 (12.7)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eOther(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e372 (4.9)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMissing(%)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e \u003cp\u003e6055 (79.1)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e96.7% records were reported from the United States. After excluding 7304 reports without weight information, 350 reports were analyzed, with median weight was 77.80 kg ([IQR] 70.0-96.4 kg). Excluding 6055 records without clearly reported treatment outcomes, 975 records (12.70%) AEs led to death, 9 records (0.19%) of disability, 227 records of hospitalization or prolonged hospital stay in (3.0%), and 16 records (0.2%) life-threatening situations(Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab3\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eTop 20 PTs with the highest frequency in Pluvicto\u0026reg; AE signal detection\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"7\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eROR(95%Cl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003ePRR(X\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eEBGM(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eIC(IC025)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eILL-DEFINED DISORDER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e547.04 ( 521.69\u0026ndash;573.61 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e366.18 ( 822186.16 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e237.1 ( 227.87 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e7.89 ( 7.83 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eGENERAL PHYSICAL HEALTH DETERIORATION\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e135.51 ( 129.33\u0026ndash;141.99 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102.09 ( 227861.3 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e88.72 ( 85.32 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.47 ( 6.4 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDEATH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e945\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.28 ( 7.74\u0026ndash;8.85 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.62 ( 5441.75 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.55 ( 7.14 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.92 ( 2.82 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eLABORATORY TEST ABNORMAL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56.91 ( 49.24\u0026ndash;65.78 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e55.84 ( 10045.46 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51.62 ( 45.73 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.69 ( 5.48 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eDISEASE PROGRESSION\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.81 ( 4.18\u0026ndash;5.54 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.74 ( 581.88 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.71 ( 4.19 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.24 ( 2.03 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMALIGNANT NEOPLASM PROGRESSION\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.49 ( 3.74\u0026ndash;5.38 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.45 ( 316.83 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.43 ( 3.8 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.15 ( 1.88 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eCOVID-19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e110\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.45 ( 1.2\u0026ndash;1.75 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.45 ( 15.33 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.45 ( 1.24 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.53 ( 0.26 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePROSTATIC SPECIFIC ANTIGEN INCREASED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56.62 ( 45.98\u0026ndash;69.71 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e56.1 ( 4844.93 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e51.85 ( 43.56 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.7 ( 5.39 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eANAEMIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.41 ( 1.97\u0026ndash;2.96 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.4 ( 76.82 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.4 ( 2.02 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.26 ( 0.96 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePLATELET COUNT DECREASED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.41 ( 3.58\u0026ndash;5.44 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.38 ( 231.1 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.36 ( 3.66 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.12 ( 1.82 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eTHROMBOCYTOPENIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e74\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.35 ( 1.87\u0026ndash;2.96 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.34 ( 56.97 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.34 ( 1.93 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.23 ( 0.89 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003ePROSTATE CANCER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.42 ( 2.7\u0026ndash;4.35 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.41 ( 115.38 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.4 ( 2.78 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.76 ( 1.41 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eILLNESS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.91 ( 2.29\u0026ndash;3.7 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.9 ( 84.4 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.89 ( 2.37 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.53 ( 1.18 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHAEMOGLOBIN DECREASED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.24 ( 3.3\u0026ndash;5.46 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.22 ( 149.31 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.2 ( 3.4 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.07 ( 1.7 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFATIGUE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e57\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.55 ( 0.42\u0026ndash;0.71 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55 ( 21.37 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.55 ( 0.44 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.87 ( -1.25 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eMALAISE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e53\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.03 ( 0.78\u0026ndash;1.35 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.03 ( 0.04 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03 ( 0.82 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.04 ( -0.36 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eHORMONE-REFRACTORY PROSTATE CANCER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121.95 ( 90.7\u0026ndash;163.96 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e121.35 ( 5254.99 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e102.89 ( 80.32 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.68 ( 6.26 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eASTHENIA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e48\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.98 ( 0.74\u0026ndash;1.3 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.98 ( 0.02 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.98 ( 0.77 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e-0.03 ( -0.44 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eSARS-COV-2 TEST POSITIVE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.95 ( 7.46\u0026ndash;13.29 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.91 ( 371.41 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.78 ( 7.69 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.29 ( 2.87 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003eFULL BLOOD COUNT DECREASED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.22 ( 8.78\u0026ndash;17 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e12.18 ( 362.86 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e11.98 ( 9.09 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e3.58 ( 3.1 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIC025: lower end of the 95% CI of the IC, EGBM05: lower end of the 95% CI of the EGBM, IC: information component, ROR: reporting odds ratio, X\u003csup\u003e2\u003c/sup\u003e: Chi-Squared Test, PTs: preferred terms, CI: confidence interval, n: number of events.\u003c/p\u003e \u003cp\u003eA total of 295 valid patient records with valid AE reports were extracted, after excluding reports with non-standardized recording and missing information, we calculated the onset time of AEs based on the start of Pluvicto\u0026reg; admission and the date of AE occurrence. The shortest onset time occurred on the same day as medication admission, and the longest onset time was 552 days, with an average of 86.29 days. The median onset time was 56 days ([IQR] 25.0-125.0 days), 289(97.9%) cases of AEs appeared within the first year of treatment, with the majority of cases occurring within the first 3 months after Pluvicto\u0026reg; treatment (n\u0026thinsp;=\u0026thinsp;190, 64.41%)(Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003eA and B).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"4. Discussion","content":"\u003cp\u003ePrior studies have highlighted other problematic aspects of Pluvicto\u0026reg; such as the drug's radiopharmaceutical mechanism, clinical trials, and analysis of clinical results, few studies have concentrated on the latest real-world research.(\u003cspan additionalcitationids=\"CR24 CR25 CR26 CR27\" citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e) A collection and evaluation Based on real-world data from large database was performed for the drug vigilance of Pluvicto\u0026reg; when it was approved by the FDA. The purpose of the study was to analyze new and meaningful AEs, guide updates to the summary of product characteristics (SmPC), and provide recommendations and evidence for clinically rational use of the drug.\u003c/p\u003e \u003cp\u003eAccording to previous clinical experience, high BMI, lack of exercise, and unhealthy lifestyle habits increase the risk of prostate cancer. Upon analyzing the demographic data, we discovered that reports containing weight information from 350 identified cases indicated a significant proportion of patients receiving Pluvicto\u0026reg; treatment had weights ranging from 60 to 100kg (273, 78%), Notably, 85 records with weights\u0026thinsp;\u0026ge;\u0026thinsp;90 kg (24.3%), indicating a higher incidence of AEs in this weight range, which may be correlate with the higher incidence of prostate cancer.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOur study analyzed 7654 AE records in the FAERS database involving Pluvicto\u0026reg; as the primary suspect drug, obtaining 649 potential AEs records at PT level. Using the detection criteria of ROR, PRR, BCPNN, and MGPS, a total of 33 AEs significant signals were identified(Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab4\" class=\"InternalRef\"\u003e4\u003c/span\u003e). After excluded 18 AE signals that did not correlate with the drug\u0026rsquo;s radiopharmaceutical effect, 15 AEs records significant signals correlated with drug effect were obtained, including laboratory test abnormal, anaemia, platelet count decreased, illness, haemoglobin decreased, full blood count decreased, dry mouth, blood test abnormal, subdural haematoma, spinal cord compression, haemoglobin abnormal, hepatic lesion, creatinine renal clearance decreased, blood creatine increased, spinal cord infection.(Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e).\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab4\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 4\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003e44 Significant AE signals at the Preferred Terms level in the FAERS database\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"6\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePT\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003en\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eROR(95%Cl)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePRR(X\u003csup\u003e2\u003c/sup\u003e)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eEBGM(EBGM05)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eIC(IC025)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eILL-DEFINED DISORDER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3487\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e547.04 ( 521.69\u0026ndash;573.61 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e366.18 ( 822186.16 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e237.1 ( 227.87 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.89 ( 7.83 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGENERAL PHYSICAL HEALTH DETERIORATION\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2616\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e135.51 ( 129.33\u0026ndash;141.99 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e102.09 ( 227861.3 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e88.72 ( 85.32 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.47 ( 6.4 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDEATH\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e945\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e8.28 ( 7.74\u0026ndash;8.85 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.62 ( 5441.75 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.55 ( 7.14 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.92 ( 2.82 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eLABORATORY TEST ABNORMAL*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e202\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.91 ( 49.24\u0026ndash;65.78 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e55.84 ( 10045.46 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.62 ( 45.73 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.69 ( 5.48 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDISEASE PROGRESSION\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e198\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.81 ( 4.18\u0026ndash;5.54 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.74 ( 581.88 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.71 ( 4.19 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.24 ( 2.03 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMALIGNANT NEOPLASM PROGRESSION\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e119\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.49 ( 3.74\u0026ndash;5.38 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.45 ( 316.83 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.43 ( 3.8 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.15 ( 1.88 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROSTATIC SPECIFIC ANTIGEN INCREASED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e97\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e56.62 ( 45.98\u0026ndash;69.71 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e56.1 ( 4844.93 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e51.85 ( 43.56 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.7 ( 5.39 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eANAEMIA*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.41 ( 1.97\u0026ndash;2.96 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.4 ( 76.82 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.4 ( 2.02 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.26 ( 0.96 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePLATELET COUNT DECREASED*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e89\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.41 ( 3.58\u0026ndash;5.44 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.38 ( 231.1 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.36 ( 3.66 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.12 ( 1.82 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROSTATE CANCER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.42 ( 2.7\u0026ndash;4.35 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.41 ( 115.38 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.4 ( 2.78 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.76 ( 1.41 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eILLNESS*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e68\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.91 ( 2.29\u0026ndash;3.7 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.9 ( 84.4 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.89 ( 2.37 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.53 ( 1.18 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAEMOGLOBIN DECREASED*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e61\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.24 ( 3.3\u0026ndash;5.46 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.22 ( 149.31 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.2 ( 3.4 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.07 ( 1.7 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHORMONE-REFRACTORY PROSTATE CANCER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e52\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e121.95 ( 90.7\u0026ndash;163.96 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e121.35 ( 5254.99 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e102.89 ( 80.32 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.68 ( 6.26 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSARS-COV-2 TEST POSITIVE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e9.95 ( 7.46\u0026ndash;13.29 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e9.91 ( 371.41 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e9.78 ( 7.69 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.29 ( 2.87 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFULL BLOOD COUNT DECREASED*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e36\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e12.22 ( 8.78\u0026ndash;17 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e12.18 ( 362.86 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e11.98 ( 9.09 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.58 ( 3.1 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eDRY MOUTH*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e32\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.26 ( 2.3\u0026ndash;4.62 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.26 ( 49.82 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.24 ( 2.43 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.7 ( 1.19 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMETASTASES TO BONE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.99 ( 3.97\u0026ndash;9.03 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.98 ( 94.53 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.93 ( 4.21 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.57 ( 1.98 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROSTATE CANCER METASTATIC\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e20\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e35.5 ( 22.64\u0026ndash;55.69 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35.44 ( 635.73 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e33.71 ( 23.13 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.07 ( 4.43 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBLOOD TEST ABNORMAL*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e17\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.32 ( 4.54\u0026ndash;11.81 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.31 ( 91.59 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.24 ( 4.85 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.86 ( 2.17 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMETASTASES TO LIVER\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.12 ( 2.52\u0026ndash;6.74 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.11 ( 37.49 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e4.09 ( 2.71 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.03 ( 1.33 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSUBDURAL HAEMATOMA*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.89 ( 2.02\u0026ndash;7.49 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3.89 ( 19.19 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.87 ( 2.24 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.95 ( 1.04 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSPINAL CORD COMPRESSION*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e14.15 ( 7.02\u0026ndash;28.5 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.14 ( 95.65 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e13.87 ( 7.72 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.79 ( 2.82 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHAEMOGLOBIN ABNORMAL*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.34 ( 3.48\u0026ndash;15.47 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7.34 ( 37.9 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.27 ( 3.9 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.86 ( 1.83 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCANCER PAIN\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.55 ( 4.71\u0026ndash;23.64 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.55 ( 51.05 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.4 ( 5.3 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.38 ( 2.28 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROSTATIC SPECIFIC ANTIGEN DECREASED\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e268.06 ( 103.99\u0026ndash;691.03 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e267.91 ( 1139.64 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e191.65 ( 86.78 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e7.58 ( 6.33 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHEPATIC LESION*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.87 ( 2.43\u0026ndash;14.15 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.86 ( 20 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.82 ( 2.79 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.54 ( 1.36 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePROSTATIC SPECIFIC ANTIGEN ABNORMAL\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.06 ( 8.24\u0026ndash;48.84 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.05 ( 87.89 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e19.5 ( 9.26 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.29 ( 3.09 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCREATININE RENAL CLEARANCE DECREASED*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.21 ( 2.16\u0026ndash;12.56 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.21 ( 16.87 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e5.18 ( 2.48 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.37 ( 1.19 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eFAILURE TO THRIVE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.89 ( 2.86\u0026ndash;16.64 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.89 ( 24.92 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.83 ( 3.27 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.77 ( 1.59 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBLOOD CREATINE INCREASED*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.56 ( 2.72\u0026ndash;15.82 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.55 ( 23.3 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e6.5 ( 3.11 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.7 ( 1.52 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMETASTASES TO SPINE\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.18 ( 4.21\u0026ndash;24.63 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10.18 ( 40.77 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e10.04 ( 4.8 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e3.33 ( 2.14 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSPINAL CORD INFECTION*\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e40.61 ( 14.8\u0026ndash;111.43 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e40.59 ( 145.64 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e38.33 ( 16.47 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.26 ( 3.93 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNEUROENDOCRINE CARCINOMA\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e17.33 ( 5.51\u0026ndash;54.52 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e17.32 ( 44.98 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e16.91 ( 6.48 )\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.08 ( 2.61 )\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eIC025 lower end of the 95% CI of the IC, EGBM05 lower end of the 95% CI of the EGBM, IC information component, ROR reporting odds ratio, X\u003csup\u003e2\u003c/sup\u003e Chi-Squared Test, PTs preferred terms, CI confidence interval, n number of events. * AEs correlate with Pluvicto\u0026reg; admission\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab5\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 5\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eDisproportionality analysis at the SOC level in FAERS Database\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSystem Organ Class(SOC)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAE Signals\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eProportion(%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eAE(cases)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eProportion(%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGENERAL DISORDERS AND ADMINISTRATION SITE CONDITIONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e7691\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e73.05\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNERVOUS SYSTEM DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e51\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.8\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRESPIRATORY, THORACIC AND MEDIASTINAL DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e24\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e87\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.83\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eGASTROINTESTINAL DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.7\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e205\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.95\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINFECTIONS AND INFESTATIONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e42\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e244\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.32\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eBLOOD AND LYMPHATIC SYSTEM DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e30\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e313\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e2.97\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINVESTIGATIONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e99\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e819\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e7.78\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEYE DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e15\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.21\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eRENAL AND URINARY DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e115\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eINJURY, POISONING AND PROCEDURAL COMPLICATIONS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e39\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e6.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e125\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e1.19\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eVASCULAR DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e49\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.47\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMETABOLISM AND NUTRITION DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e28\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e94\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.89\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePSYCHIATRIC DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e19\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e35\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.33\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eNEOPLASMS BENIGN, MALIGNANT AND UNSPECIFIED (INCL CYSTS AND POLYPS)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e375\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e3.56\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCARDIAC DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e58\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.55\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eHEPATOBILIARY DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e21\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e47\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.45\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eMUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e26\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.0\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e76\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.72\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSKIN AND SUBCUTANEOUS TISSUE DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e16\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e23\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.22\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eENDOCRINE DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.03\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eEAR AND LABYRINTH DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003ePRODUCT ISSUES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e9\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.09\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eCONGENITAL, FAMILIAL AND GENETIC DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eREPRODUCTIVE SYSTEM AND BREAST DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.6\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.04\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eSOCIAL CIRCUMSTANCES\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.01\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eIMMUNE SYSTEM DISORDERS\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.3\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eTotal\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e649\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e100.00\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e10528\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e100.00\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eAE, Adverse Event. SOC, System Organ Class.\u003c/p\u003e \u003cp\u003eDisproportionality analysis revealed that the most frequently reported and clinically significant signals at the System Organ Class (SOC) level comprised general disorders and administration site conditions (n\u0026thinsp;=\u0026thinsp;7,691, 73.05%), investigations (n\u0026thinsp;=\u0026thinsp;819, 7.78%), and neoplasms benign, malignant and unspecified (including cysts and polyps) (n\u0026thinsp;=\u0026thinsp;375, 3.56%) (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e and Table\u0026nbsp;\u003cspan refid=\"Tab5\" class=\"InternalRef\"\u003e5\u003c/span\u003e). Notably, several adverse events (AEs) within these SOC categories\u0026mdash;including death, malignant neoplasm progression, hormone-refractory prostate cancer, asthenia, prostate cancer, and bone metastases\u0026mdash;were absent from the Pluvicto\u0026reg; Summary of Product Characteristics (SmPC) and appear more likely attributable to underlying disease progression than direct pharmacological effects. Nevertheless, our analysis identified drug-related AEs (Preferred Terms: fatigue, dry mouth, anemia, pancytopenia, etc) demonstrating temporal and pharmacological plausibility with Pluvicto\u0026reg; administration, consistent with the U.S. Food and Drug Administration (FDA) Adveres Event Documentation. While Pluvicto\u0026reg;s therapeutic mechanism involves targeted delivery of ionizing radiation, causal attribution of tumor metastasis/progression to the radiopharmaceutical requires rigorous clinical-pathological correlation. Clinicians should conduct comprehensive benefit-risk assessments, ensuring radiation exposure risks remain substantially below baseline oncological risks.\u003c/p\u003e \u003cp\u003eSeveral AEs were thought to be related to blood and lymphatic system disorders, particularly those involving red blood cells, hemoglobin, platelet reduction, total blood cell reduction, and bone marrow failure, all of which indicate the inhibitory effect of Pluvicto\u0026reg; on hematopoietic system function. In the Pluvicto\u0026reg; SmPC, blood and lymphatic system abnormalities include anemia, thrombocytopenia, leukopenia, neutropenia, and pancytopenia. Prior clinical trials have all demonstrated that abnormalities in the blood and lymphatic systems were common and complex AEs of Pluvicto\u0026reg;. Pooled clinical data(VISION phase III [NCT03511664] (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) TheraP phase II [NCT03392428] (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e), LuPSMA [NCT03828838] (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)) demonstrate dose-dependent hematologic toxicity profiles. The VISION study(phase III [NCT03511664])(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) was a randomized phase III clinical trial that compared the efficacy of Pluvicto\u0026reg; combined with Best Standard of Care (BSoC) versus BSoC alone (including, but not limited to, approved hormonal therapies, bisphosphonates, radiation therapy, Denosumab, and any dose of glucocorticoids). Patients who received Pluvicto\u0026reg; treatment demonstrated significantly superior outcomes in imaging-based progression-free survival and overall survival compared to the control group, underscoring its treatment efficacy. However, Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 hematologic ADRs were substantially more prevalent with Pluvicto\u0026reg; versus controls: anemia (12.9% vs 3.8%), thrombocytopenia (7.9% vs 0.5%), lymphocytopenia (7.8% vs 0%), neutropenia (4.5% vs 0.2%), with two fatal pancytopenia events (1.1%). These results were consistent with the findings of Michael S Hofman et al (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) in the Phase II TheraP trial. In the TheraP trial, Michael et al. compared Pluvicto\u0026reg; to cabazitaxel, a second-generation semisynthetic microtubule inhibitor that stabilizes microtubules and induces tumor cell death. In their study, Pluvicto\u0026reg; was more effective relative to cabazitaxel in patients with metastatic castration-resistant prostate cancer. Regarding AEs, it was noteworthy that the incidence of severe adverse events (SAEs, GRADE 3/4) with Pluvicto\u0026reg; was lower than with cabazitaxel, with 32 cases (33%) of SAEs among 98 males treated with Pluvicto\u0026reg; and 45 cases (53%) among 85 males treated with cabazitaxel. Grade 3/4 neutropenia was less common with Pluvicto\u0026reg; (4% vs. 13%), but Grade 3/4 thrombocytopenia induced by Pluvicto\u0026reg; was more common than cabazitaxel (11% vs. 0%). The mechanism of bone marrow suppression and hematologic and lymphatic system abnormalities caused by Pluvicto\u0026reg; may involve multiple contributing factors. Similar AEs were also reported in the LuPSMA trial,(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) with thrombocytopenia being the most common AE, aside from mild discomfort symptoms (such as dry mouth and dry eyes). This study found that the reporting frequency of thrombocytopenia in a large sample database was higher than that of other symptoms, such as dry mouth, nausea, and fatigue, suggesting that thrombocytopenia in some patients may be attributed to bone marrow infiltration by prostate cancer metastasis rather than to Pluvicto\u0026reg; admission. Michael Hofmann et al (\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e) performed bone marrow biopsies on 3 patients in the LuPSMA trial, revealing extensive prostate cancer infiltration in the bone marrow. Pluvicto\u0026reg; is a radio-labeled small molecule with high affinity for the enzymatic active site of PSMA, enabling highly targeted beta radiation delivery to prostate cancer cells. The presence of prostate cancer infiltration in the bone marrow implies blurred boundaries between normal bone marrow and tumors, which leads to radiation exposure of both normal bone marrow tissue and tumors by Pluvicto\u0026reg;, resulting in hematologic suppression and bone marrow damage. Violet et.al (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e) also reported leukoerythroblastic pancytopenia as the primary dose-limiting toxicity (DLT) in patients with diffuse marrow infiltration, manifesting as leuko-erythroblastic pancytopenia, sufficient to cause cessation of Pluvicto\u0026reg; treatment. Existing clinical trial results indicated that most patients received chemotherapy or hormone therapy before Pluvicto\u0026reg; treatment, suggesting that prior treatments may have reduced patients' bone marrow reserves, and exacerbated hematologic lymphatic system damage after Pluvicto\u0026reg; admission. Hematologic and lymphatic system AEs were also correlated with other more severe AEs, thrombocytopenia and marrow failure may increase the incidence of subdural hematoma and gingival bleeding, while pancytopenia and marrow failure lead to decreased immune function, increasing the risk of infection. Our study identified multiple serious adverse events (SAEs) within hematolymphatic system disorder, including anemia (2.41, 95%CI 1.97\u0026ndash;2.96), pancytopenia (2.27, 95%CI 1.63\u0026ndash;3.16), myelosuppression (0.96, 95%CI 0.62\u0026ndash;1.47), bone marrow failure (1.88, 95%CI 0.7-5.00), disseminated intravascular coagulation (DIC) (1.12, 95%CI 0.36\u0026ndash;3.46), and thrombotic microangiopathy (TMA) (0.87, 95%CI 0.28\u0026ndash;2.71). These findings necessitate risk-adapted therapeutic algorithms: Pre-treatment bone marrow reserve quantification via hybrid imaging (\u0026sup1;⁸F-FDG PET/CT) and metastatic burden stratification using circulating tumor DNA (ctDNA) analysis should be mandated to optimize therapeutic index during clinical decision-making.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTo analyze the temporal relationship between adverse events (AEs) and onset time, we systematically evaluated AEs across different time periods at the System Organ Class (SOC) level. For SOCs with \u0026ge;\u0026thinsp;5 AEs, Pearson's χ\u0026sup2; test was applied; otherwise, Fisher's exact test was employed to enhance analytical precision (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e). Notably, the \"Investigations\" SOC demonstrated significant signals across all time intervals except at 30 and 60 days. The early event proportion for this SOC exceeded 50% from day 90 onward, indicating that over half of AEs categorized under \"Investigations\" (e.g., Laboratory test abnormal [n\u0026thinsp;=\u0026thinsp;202], Prostatic specific antigen increased [n\u0026thinsp;=\u0026thinsp;97], Platelet count decreased [n\u0026thinsp;=\u0026thinsp;89]) occurred within the first three months post-Pluvicto\u0026reg; administration, underscoring the necessity for intensified laboratory monitoring of clinical test results during initial treatment phases.\u003c/p\u003e \u003cp\u003eOur analysis identified previously underrecognized infection-related AEs. The Infections and Infestations SOC demonstrated positive signals at 15, 30, 150, and 180 days, with 63.1% of Preferred Terms (PTs) concentrated in three categories: COVID-19 (n\u0026thinsp;=\u0026thinsp;110, ROR 1.95, 95% CI 1.32\u0026ndash;2.88), pneumonia (n\u0026thinsp;=\u0026thinsp;27, ROR 3.45, 95% CI 2.11\u0026ndash;5.63), and urinary tract infection (n\u0026thinsp;=\u0026thinsp;17, ROR 2.78, 95% CI 1.65\u0026ndash;4.69). These findings advocate for prophylactic measures against pathogen exposure during early-phase treatment (\u0026le;\u0026thinsp;30 days) and late-phase follow-up (150\u0026ndash;180 days), particularly targeting respiratory and genitourinary systems. Interestingly, Hepatobiliary Disorders SOC exhibited significant signals during the first treatment cycle (6 weeks), with early event proportions consistently exceeding 50%, suggesting first-dose predisposition. While only hepatic lesion (n\u0026thinsp;=\u0026thinsp;5, ROR 5.87, 95% CI 2.43\u0026ndash;14.15) met all four signal detection algorithms, this SOC encompassed Grade 3/4 adveres events (hepatic failure [n\u0026thinsp;=\u0026thinsp;5], hepatic cytolysis[n\u0026thinsp;=\u0026thinsp;2], hepatotoxicity [n\u0026thinsp;=\u0026thinsp;2]), necessitating baseline hepatic function screening to mitigate severe adverse outcomes.\u003c/p\u003e \u003cp\u003eOther SOCs (Musculoskeletal/Connective Tissue Disorders, Cardiac Disorders, Nervous System Disorders, Gastrointestinal Disorders) also exhibited limited case numbers and low early event frequencies. These preliminary observations require validation through larger cohort studies to minimize potential type II errors.\u003c/p\u003e \u003cp\u003eFurthermore, the LuPSMA trial demonstrated that Pluvicto\u0026reg; appeared to induce rapid and clinically meaningful pain relief, with 27 patients (37%) achieving symptomatic improvement following the first treatment cycle, surpassing the 9% pain relief observed in cabazitaxel-treated patients from the TROPIC trial.(\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) In metastatic castration-resistant prostate cancer (mCRPC), pain pathogenesis primarily stems from osteoblastic bone metastases, lumbosacral infiltration, and neural compression, while also correlating with reduced overall survival. Skeletal involvement remains highly prevalent in this population, frequently causing debilitating pain, symptomatic skeletal events (SSEs), functional impairment, quality of life deterioration, and mortality. Our study corroborates these findings, within the Musculoskeletal and Connective Tissue Disorders System Organ Class (SOC), Preferred Terms (PTs) associated with somatic pain represented a minimal proportion of reports (n\u0026thinsp;=\u0026thinsp;45, 0.43%). Notably, none of these pain-related PTs demonstrated significant safety signals when analyzed through our four distinct pharmacovigilance algorithms (including ROR, PRR, MGPS and BCPNN). Fizazi et al demonstrated that symptomatic skeletal events (SSEs) significantly exacerbated pain severity and compromised quality of life metrics in patients with metastatic castration-resistant prostate cancer (mCRPC) and bone metastases.(\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) Comparative efficacy data from the TheraP trial revealed a higher incidence of Grade 3/4 pain with Pluvicto\u0026reg; versus cabazitaxel (11% [14/127] vs 5% [6/126]).(\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) In the predefined subgroup of 178 patients with baseline Present Pain Intensity (PPI) scores\u0026thinsp;\u0026ge;\u0026thinsp;2 (Pluvicto\u0026reg;: n\u0026thinsp;=\u0026thinsp;80; cabazitaxel: n\u0026thinsp;=\u0026thinsp;98), pain responses were observed in 60% (48/80) versus 43% (42/98) respectively. In the CARD study, cabazitaxel plus abiraterone or enzalutamide delayed the time to the first symptomatic skeletal event in patients with metastatic castration-resistant prostate cancer and improved pain response but did not delay the time to FACT-P score deterioration. In the COMET-1 and COMET-2 studies, cabozantinib delayed the time to the first symptomatic skeletal event in patients with metastatic castration-resistant prostate cancer when compared to prednisone. (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e) Notably, the VISION trial reported Pluvicto\u0026reg; delayed median time to first SSE or death compared to standard care (11.5 vs 6.8 months; HR\u0026thinsp;=\u0026thinsp;0.50, 95% CI 0.40\u0026ndash;0.62).(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e) Furthermore, Pluvicto\u0026reg; reduced incidence of spinal cord compression - the most debilitating SSE subtype (3.7% vs 6.5%), supporting optimized analgesic strategies during treatment.\u003c/p\u003e \u003cp\u003eRegarding AEs associated with troublesome symptoms, this study demonstrated that although these symptoms were frequently reported and substantially impacted patients' subjective experiences during Pluvicto\u0026reg; (lutetium Lu 177 vipivotide tetraxetan) therapy, only xerostomia (n\u0026thinsp;=\u0026thinsp;29) fulfilled the criteria across all four analytical algorithms. Other burdensome symptoms - including fatigue (n\u0026thinsp;=\u0026thinsp;54), nausea (n\u0026thinsp;=\u0026thinsp;35), discomfort (n\u0026thinsp;=\u0026thinsp;35), asthenia (n\u0026thinsp;=\u0026thinsp;32), decreased appetite (n\u0026thinsp;=\u0026thinsp;24), vomiting (n\u0026thinsp;=\u0026thinsp;21), diarrhea (n\u0026thinsp;=\u0026thinsp;13), and constipation (n\u0026thinsp;=\u0026thinsp;10) - predominantly met the criteria specific to the Multi-item Gamma Poisson Shrinker (MGPS) algorithm.\u003c/p\u003e \u003cp\u003eIn the TheraP trial, Hofman et al. (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e) compared Pluvicto\u0026reg; with cabazitaxel and observed lower incidence rates of treatment-emergent troublesome symptoms with Pluvicto\u0026reg;, including diarrhea (31% vs 55%), urinary symptoms (38% vs 62%), dizziness/vertigo (38% vs 53%), dysgeusia (54% vs 69%), alopecia (10% vs 42%), rash (14% vs 32%), and palmar-plantar erythrodysesthesia (35% vs 43%). The AE profiles reported in the VISION study and LuPSMA trial aligned with these findings, though incidence rates substantially exceeded those in the FDA Adverse Event Reporting System (FAERS) database. This discrepancy may stem from differential reporting practices, as some trials potentially categorized certain manifestations as non-specific disorders rather than troublesome symptoms.(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e)\u003c/p\u003e \u003cp\u003eDue to the highly targeted and short-range β particle radiation characteristics of Pluvicto\u0026reg; (lutetium Lu 177 vipivotide tetraxetan), physiological sites expressing prostate-specific membrane antigen (PSMA), such as salivary and lacrimal glands, may also be affected, thereby explaining characteristic AEs (e.g., dry mouth and dry eyes). While most troublesome symptoms remain self-limited, supportive measures including artificial tears, anti-diarrheals, and antiemetics are recommended for symptomatic management.\u003c/p\u003e"},{"header":"5. Conclusion","content":"\u003cp\u003eThrough our comprehensive pharmacovigilance analysis of the FAERS database, we underscores the the risk profile and significant AE signals with Pluvicto\u0026reg; (lutetium Lu 177 vipivotide tetraxetan) as the primary suspect drug. Our study confirms dose-dependent hematologic toxicity, with Grade\u0026thinsp;\u0026ge;\u0026thinsp;3 anemia (12.9%), thrombocytopenia (7.9%), and lymphocytopenia (7.8%) prominently observed in pooled clinical trial data (VISION, TheraP, LuPSMA), consistent with prior reports. Notably, thrombocytopenia emerged as a recurrent adverse event (AE), potentially attributable to direct radiation-induced bone marrow suppression and preexisting metastatic infiltration, as evidenced by histopathologic confirmation of marrow involvement in subset analyses. Temporal SOC analysis revealed abnormal laboratory investigations and hepatobiliary disorders predominantly manifested within initial treatment cycles (\u0026le;\u0026thinsp;90 days), necessitating vigilant laboratory monitoring during early phases. Infections and infestations, particularly COVID-19 (ROR 1.95), pneumonia (ROR 3.45), and urinary tract infections (ROR 2.78), exhibited biphasic susceptibility peaks (\u0026le;\u0026thinsp;30 and 150\u0026ndash;180 days), advocating targeted prophylactic measures. While troublesome symptoms (dry mouth, fatigue, nausea, etc) were frequently reported, only xerostomia met all signal detection criteria, reflecting PSMA-targeted radiation effects on salivary/lacrimal glands. However, limitations including ascertainment bias and confounding by disease progression necessitate validation through larger cohort studies. Future research should prioritize mechanistic studies to disentangle drug-related hemato-lymphologic toxicity, hepatobiliary disorders and potential infestation risks, while preserving Pluvicto\u0026reg;\u0026rsquo;s survival benefits in advanced prostate cancer patients, optimize risk-adapted therapeutic strategies for high-risk population.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdverse Event\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFAERS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFDA Adverse Event Reporting System\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eFDA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eFood and Drug Administration\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePSMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProstate-Specific Membrane Antigen\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eROR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eReporting Odds Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePRR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eProportional Reporting Ratio\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBCPNN\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBayesian Confidence Propagation Neural Network\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMGPS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMulti-item Gamma Poisson Shrinker\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMedDRA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eMedical Dictionary for Regulatory Activities\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSOC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSystem Organ Class\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003ePT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ePreferred Term\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eTMA\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eThrombotic Microangiopathy\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSmPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSummary of Product Characteristics\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSAE\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSevere Adverse Event\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eBMI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eBody Mass Index\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAdverse Drug Reaction\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eConfidence Interval\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIQR\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInterquartile Range\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eEBGM\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eEmpirical Bayes Geometric Mean\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eIC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eInformation Component\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003eEthics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eInstitutional review board approval was waived for this study because FAERS is a public anonymized database.\u003c/p\u003e\n\u003cp\u003eConsent for publication\u003c/p\u003e\n\u003cp\u003eData that support the findings of this study is obtained from the FDA Adverse Event Reporting System (FAERS) database that was provided by the FDA. No individual patient consent was required for the publication of this study.\u003c/p\u003e\n\u003cp\u003eAvailability of data and materials\u003c/p\u003e\n\u003cp\u003eThe data that support the findings of this study are available from the FDA Adverse Event Reporting System (FAERS) database (https://www.fda.gov/drugs/drug-approvals-and-databases/fda-adverse-event-reporting-system-faers-database). No datasets were generated during the current study.\u003c/p\u003e\n\u003cp\u003eCompeting interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that they have no competing interest.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis study was supported by the National Key R\u0026amp;D Program of China (Grant No. 2023YFC2507000), the National Natural Science Foundation of China (Grant No. 82072833 and No. 82272864 to Hao Ping), Capital\u0026rsquo;s Funds for Health Improvement and Research (Grant No. 2024-2-2059).\u003c/p\u003e\n\u003cp\u003eAuthors\u0026rsquo; contributions\u003c/p\u003e\n\u003cp\u003eY. J. and Y.Z. had full access to all the data in the study and took responsibility for the integrity of the data analysis. Concept design: Y.J., M.W., Y.Z.. Acquisition, analysis, and interpretation of data: All authors. Critical revision of the manuscript: All authors. Administrative, technical, or material support: N.X., H.P.. Supervision: N.X., H.P..\u003c/p\u003e\n\u003cp\u003e*Y.J., Y.Z. and M.W. have made equal contributions to the development and preparation of this manuscript.\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThis study was performed using the FDA Adverse Event Reporting System (FAERS) database that was provided by the FDA. The information, results, or interpretation of the current study do not represent any opinion of the FDA.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin. 2023;73:17\u0026ndash;48.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSartor O, et al. Lutetium-177-PSMA-617 for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2021;385:1091\u0026ndash;103.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatrikidou A, et al. Who dies from prostate cancer? Prostate Cancer Prostatic Dis. 2014;17:348\u0026ndash;52.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer Stat 2022 CA: Cancer J Clin 72, (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScher HI, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187\u0026ndash;97.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRyan CJ, et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015;16:152\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eFizazi K, et al. Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2012;13:983\u0026ndash;92.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAttard G, et al. Abiraterone acetate and prednisolone with or without enzalutamide for high-risk non-metastatic prostate cancer: a meta-analysis of primary results from two randomised controlled phase 3 trials of the STAMPEDE platform protocol. Lancet (London England). 2022;399:447\u0026ndash;60.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBeer TM, et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. 2014;371:424\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhai Z, et al. Incidence and disease burden of prostate cancer from 1990 to 2017: Results from the Global Burden of Disease Study 2017. Cancer. 2020;126:1969\u0026ndash;78.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBostwick DG, Pacelli A, Blute M, Roche P, Murphy GP. Prostate specific membrane antigen expression in prostatic intraepithelial neoplasia and adenocarcinoma: a study of 184 cases. Cancer. 1998;82:2256\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMinner S, et al. High level PSMA expression is associated with early PSA recurrence in surgically treated prostate cancer. Prostate. 2011;71:281\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRowe SP, Gorin MA, Pomper MG. Imaging of Prostate-Specific Membrane Antigen with Small-Molecule PET Radiotracers: From the Bench to Advanced Clinical Applications. Annu Rev Med. 2019;70:461\u0026ndash;77.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAfshar-Oromieh A, et al. The Theranostic PSMA Ligand PSMA-617 in the Diagnosis of Prostate Cancer by PET/CT: Biodistribution in Humans, Radiation Dosimetry, and First Evaluation of Tumor Lesions. J Nuclear Medicine: Official Publication Soc Nuclear Med. 2015;56:1697\u0026ndash;705.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eViolet J, et al. Dosimetry of 177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: Correlations Between Pretherapeutic Imaging and Whole-Body Tumor Dosimetry with Treatment Outcomes. J Nuclear Medicine: Official Publication Soc Nuclear Med. 2019;60:517\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHennrich U, Eder M. [177Lu]Lu-PSMA-617 (PluvictoTM): The First FDA-Approved Radiotherapeutical for Treatment of Prostate Cancer. Pharmaceuticals (Basel Switzerland) 15, (2022).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChen C, et al. Cardiotoxicity Induced by Immune Checkpoint Inhibitors: A Pharmacovigilance Study From 2014 to 2019 Based on FAERS. Front Pharmacol. 2021;12:616505.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBrown EG. Using MedDRA: implications for risk management. Drug Saf. 2004;27:591\u0026ndash;602.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRothman KJ, Lanes S, Sacks ST. The reporting odds ratio and its advantages over the proportional reporting ratio. Pharmacoepidemiol Drug Saf. 2004;13:519\u0026ndash;23.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eEvans SJ, Waller PC, Davis S. Use of proportional reporting ratios (PRRs) for signal generation from spontaneous adverse drug reaction reports. Pharmacoepidemiol Drug Saf. 2001;10:483\u0026ndash;6.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eBate A, et al. A Bayesian neural network method for adverse drug reaction signal generation. Eur J Clin Pharmacol. 1998;54:315\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003evan Puijenbroek EP et al. A comparison of measures of disproportionality for signal detection in spontaneous reporting systems for adverse drug reactions. Pharmacoepidemiol Drug Saf 11, (2002).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGroener D et al. Impact of [177Lu]Lu-PSMA-617 Radioligand Therapy on Reference Organ Uptake Assessed by [68Ga]Ga-PSMA-11-PET/CT. Cancers 15, (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMehrens D et al. Cost-Effectiveness Analysis of 177Lu-PSMA-617 Radioligand Therapy in Metastatic Castration-Resistant Prostate Cancer. J Natl Compr Cancer Network: JNCCN 21, (2023).\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePatell K, et al. Lutetium-177 PSMA for the treatment of metastatic castrate resistant prostate cancer: a systematic review. Expert Rev Anticancer Ther. 2023;23:731\u0026ndash;44.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRamnaraign B, Sartor O. PSMA-Targeted Radiopharmaceuticals in Prostate Cancer: Current Data and New Trials. Oncologist. 2023;28:392\u0026ndash;401.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSch\u0026auml;fer H, et al. Extensive 177Lu-PSMA Radioligand Therapy Can Lead to Radiation Nephropathy with a Renal Thrombotic Microangiopathy-like Picture. Eur Urol. 2023;83:385\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eGiunta EF, et al. 177Lu-PSMA therapy in metastatic prostate cancer: An updated review of prognostic and predictive biomarkers. Cancer Treat Rev. 2024;125:102699.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHofman MS, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet (London England). 2021;397:797\u0026ndash;804.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHofman MS, et al. [177Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825\u0026ndash;33.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLawton CA, et al. Late renal dysfunction in adult survivors of bone marrow transplantation. Cancer. 1991;67:2795\u0026ndash;800.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSaha BK, Saha A, Chong W, Beegle S. A Fatal Case of Thrombotic Microangiopathy Without Schistocytosis and Absent Biochemical Markers of Hemolysis. Am J Med Sci. 2020;359:296\u0026ndash;302.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eSonpavde GP, et al. Cabozantinib for Progressive Metastatic Castration-resistant Prostate Cancer Following Docetaxel: Combined Analysis of Two Phase 3 Trials. Eur Urol Oncol. 2020;3:540\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-cancer","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bcan","sideBox":"Learn more about [BMC Cancer](http://bmccancer.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bcan/default.aspx","title":"BMC Cancer","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Pluvicto®, Lutetium-177–PSMA-617, lutetium (177Lu) vipivotide tetraxetan, FAERS, Adverse event, Data mining","lastPublishedDoi":"10.21203/rs.3.rs-6084374/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6084374/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eObjective\u003c/strong\u003e Pluvicto® (Lutetium-177–PSMA-617) was the world's first radiolabeled drug for the treatment of metastatic castration-resistant prostate cancer that was positive for prostate-specific membrane antigen with limited global use to date. Our study aimed to conduct a thorough analysis based on the adverse event reporting system FAERS of the Food and Drug Administration (FDA), providing insights for its future clinical application.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods \u003c/strong\u003eThe adverse event reports suspected primarily of Pluvicto® from April 1, 2022 to December 31, 2024 were retrieved from the FAERS system to conduct a disproportionality test. The characteristics of these reports were analyzed including demographic features, time of adverse event occurrence, and features of adverse events. Adverse events (AEs) were classified by System Organ Classes (SOCs) and preferred terms (PTs) according to the Medical Dictionary for Regulatory Activities (MedDRA®). The disproportionality of results was analyzed by Reporting Odds Ratio (ROR), Proportional Reporting Ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), and Multi-item Gamma Poisson Shrinker (MGPS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults \u003c/strong\u003eA total of 7654 adverse event reports suspected primarily of Pluvicto® were submitted to the database, showing a monthly increasing trend in report numbers. 649 Preferred Terms (PTs) were identified, and after screening, from which 33 significant PT signals were identified by the 4 algorithms, involving 10 SOCs after classification. Additionally, our study revealed thrombotic microangiopathy (TMA) as an adverse event not previously documented in the label.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions \u003c/strong\u003eThe study confirmed the majority of significant AE signals that have been listed in the prescribing information or reported in previous studies. 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