Comparative analysis of PSMA PET-CT: Assessing prostate cancer activity without CT findings

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Timely diagnosis and treatment are crucial for survival, with higher rates in developed countries. 68 Ga-PSMA PET-CT aids in identifying metastatic disease, guiding personalized treatment strategies. The aim of this study is to compare the uptake of the radiotracer 68 Ga-PSMA in primary and metastatic prostate cancer lesions identified on PSMA PET-CT against conventional CT (Computed Tomography) in staging prostate cancer patients. METHODS A retrospective, cross-sectional study was conducted in the PET-CT Unit. Seventy-one patients diagnosed with prostate cancer by histopathology who underwent PSMA PET-CT scan and who were referred for CT staging were included. The study variables were the determination of the maximum standardized uptake value (SUVmax), and the anatomic location of lesions detected by 68 Ga-PSMA in bone, lymph node, prostate, and lung. Lesions were classified as seen by PSMA PET-CT or by both PSMA PET-CT and conventional Computed Tomography. RESULTS A total of 113 lesions of tumoral activity were identified: 70 lesions were detected only with 68 Ga-PSMA PET-CT with a mean SUVmax of 14.14 ± 11.25, in contrast to a mean SUVmax of 23.15 ± 20.51 in 43 lesions detected by both PSMA PET-CT and conventional CT. (p = 0.049). CONCLUSION Positive 68 Ga-PSMA PET-CT showed metastatic disease that otherwise would have not been diagnosed in patients undergoing conventional CT, which corresponds to an upstaging in 67% of patients. These results are relevant due to the limited availability of PET-CT equipment in global south countries. Diagnostic precision Staging PET-TC Prostate Cancer PSMA Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Prostate cancer (PCa) ranks as the most prevalent neoplasm among men globally [ 1 , 2 ], particularly in developed countries, correlating with advancing age [ 3 ]. In Mexico, its incidence in 2022 reached 39.1 per 100,000, establishing it as the predominant cancer in the male population [ 4 ]. Additionally, upon diagnosis, they are categorized as advanced with an unfavorable prognosis. Timely diagnosis and treatment are identified as the crucial factors associated with lower mortality rates in developed nations. When diagnosed with early screening, the 5-year survival rate nears 100%, in stark contrast to the 40% observed in developing countries. [ 5 ]. PCa can also affect transgender women, as the prostate is usually conserved after gender-confirming surgery, but it is not clear how common it is in this population. [ 6 ] Furthermore, PCa represents a significant global health challenge, marked by numerous instances of biochemical relapse post-radical treatment. Hence, in cases of PCa recurrence, timely diagnosis becomes crucial for implementing effective rescue therapy [ 7 , 8 ]. The precision of 68 Ga-PSMA PET-CT plays a pivotal role in identifying patients harboring occult distant metastatic disease, offering a valuable tool for developing personalized multimodal treatment strategies, particularly in the context of oligometastatic disease [ 9 , 10 ]. The SUVmax value demonstrates a correlation with the grade classification of prostate cancer [ 11 ], thereby serving as a predictive indicator for the differentiation of tumoral tissue. Limited literature exists on the association between the uptake of the radiotracer 68 Ga-PSMA in detecting tumor activity in PET-CT and its correlation with or without tomographic changes [ 11 – 12 ]. This study aimed to examine the presence of tomographic evidence of prostate cancer lesions in patients exhibiting uptake of 68 Ga-PSMA PET CT. METHODS This cross-sectional study was conducted in the PET-CT Unit at the University Center of Radiology and Diagnostic Imaging of the Hospital Universitario “Dr. Jose E. Gonzalez” in Monterrey, Nuevo Leon, Mexico. Patients were included to evaluate primary prostate cancer with a 68 Ga-PSMA PET-CT scan. Negative PET-CT results were excluded. Study population and variables The study variables were the determination of the maximum standardized uptake value (SUVmax), and the anatomic location of lesions detected by 68 Ga-PSMA in bones, lymph nodes, prostate, and lungs. Imaging studies were classified as 68 Ga-PSMA PET-CT positive with tomographic evidence or 68 Ga-PSMA PET-CT positive without tomographic evidence. Definitions 68 Ga-PSMA PET-CT without tomographic evidence: radiotracer uptake by tumoral activity quantified by SUVmax and seen exclusively in the PET modality. 68 Ga-PSMA PET-CT with tomographic evidence: The radiotracer uptake in the PET modality was associated with structural changes according to RRECIST 1.1 criteria [ 13 ] due to tumor lesions identified in the CT modality. In 68 Ga-PSMA PET-CT studies with two or more lesions in the same location variable (e.g. “lymph nodes”), the lesion with the highest uptake in each patient was selected based on the SUVmax at each anatomic site. Imaging protocol Imaging protocol All patients underwent PET-CT on a Discovery Elite 690 system (GE Healthcare), which combines a high-resolution PET scanner with lutetium-yttrium oxyorthosilicate (LYSO) crystals and a 16-slice CT. The average administered activity of ^68Ga-PSMA was 1.8–2.2 MBq/kg, and imaging acquisition was performed 60 minutes after intravenous injection. Patients received 1 L of water orally before the scan; in those with a history of prostatectomy, diluted non-ionic iodine contrast was administered orally with water. The CT acquisition was performed first, immediately before the PET scan, with the following technical parameters: tube potential 120 kV; mA automatically adjusted according to patient weight and height using the Care 2® application; pitch 0.75; rotation time 0.5 s; slice thickness 3 mm; slice interval 3 mm; and field of view (FOV) 500 mm. A diagnostic CT scan was obtained in the portal venous phase, 80 s after intravenous injection of iodinated contrast agent (Imeron 300). PET images were then acquired in whole-body 3D mode (from skull base to mid-thigh), with two minutes per bed position. Reconstructions were performed using four iterations and 14 subsets, with an image matrix of 168 × 168, Gaussian filter, and zoom value of 1. Attenuation and scatter correction were applied using the CT data. 68 Ga PSMA uptake analysis The PET-CT images were analyzed without blinding by a radiologist with experience of seven years in PET-CT and a radiology and imaging resident in training. SUVmax was determined using 2D regions of interest adjusted for size. In a PET, any focal uptake of 68 Ga-PSMA higher than the surrounding background and not associated with physiologic uptake was considered indicative of malignancy. RECIST 1.1 criteria were followed to determine lesions suspicious for tumor activity on CT, including lymph nodes, bone, and lung [ 13 ]. Statistical analysis The detection rate, defined as the number of studies with at least one tumor lesion, was divided into 68 Ga-PSMA PET-CT with and without tomographic evidence and then plotted against SUVmax. Two-sided Mann-Whitney U tests were used to evaluate differences in SUVmax values between the groups with and without tomographic evidence. All tests were two-sided with a significant p-value of 0.05. The statistical analysis was performed using SPSS version 25. (IBM Corp. Armonk, NY, USA). Ethical Considerations This study received prior review and approval from the corresponding Ethics and Research Committees, under registration number AH21-00024, ensuring compliance with the Helsinki Declaration as well as national and international research standards. The authors declare no financial or commercial gain from this study and have no conflicts of interest. All imaging studies utilized were not conducted specifically for this research. Informed consent was not required since the information was collected during routine clinical care and the study was retrospective in nature. RESULTS A total of 71 positive PET-CT studies from men diagnosed with prostate cancer were included, with a mean age of 64.9 ± 7.5. From those studies, 113 lesions were identified, as some patients had lesions at two or more sites. There were 70 (61.9%) lesions with positive 68 Ga-PSMA PET-CT without tomographic evidence and 43 (38.1%) with tomographic evidence. Tumoral activity was detected in the prostate (n 71, 62.8%), lymph nodes (n 17, 15%), bone (n 14, 12.4%), and lungs(n 11, 9.7%). (Table 1 ). Table 1 Comparison between lesions detected by 68Ga-PSMA PET-CT with and without tomographic evidence. Lesions detected by 68 Ga-PSMA PET-CT With CT changes Without CT changes p-value N (%) SUVmax N (%) SUVmax Overall lesions 43 (38) 18.4 [8.7–34.5] 70 (62) 8 [4.8–14.9] 0.001* Bone 12 (27.9) 24.3 [9-48.5] 2 (2.8) 4.7 [4.5–4.7] 0.144 Lymph nodes 13 (30.3) 17.2 [6.5–50.8] 4 (5.5) 7.7 [5.4–8.7] 0.113 Prostate and prostatic bed 11 (25.6) 14.7 [9.9–18.4] 60 (86.1) 11.7 [6.2–20] 0.4 Lungs 7 (16.3) 30.7 [14.6–52.4] 4 (5.5) 4.3 [2.2–7.8] 0.008* CT – Computed Tomography. Data is presented as frequencies and percentages in parentheses or median and interquartile range in brackets. The overall lesion value was calculated as the mean SUVmax of the presented lesions or as the SUVmax of a single lesion if only one was present. Mann-Whitney Test was used to compare SUVmax between those with and without tomographic evidence. W-With; WO – Without; CT – Computed Tomography. *p < 0.05 Prostate lesions most frequently lacked tomographic evidence in comparison to the other lesions (n = 60/70, 86%). In the group with tomographic evidence, the frequency of lesions was homogeneous, although lungs’ lesions were less frequent than the rest. (Fig. 1 , 2 , 3 ) 68 Ga-PSMA PET-CT uptake was similar between all those lesions with and without tomographic evidence. Lungs were the exception, in which SUVmax was significantly higher whenever there was tomographic evidence of lesions (MD = 29.9; 95% CI = 8.3–51.6; p-value = 0.008) (Table 1 ). There were 68 out of 71 (95.7%) patients with PSA value available, with a wide range of 1.3 ng/mL to 665 ng/mL. The median PSA was 11.7 [IQR: 8-24.7] ng/mL. In patients with tomographic evidence of lesions, there was a PSA median of 27.6 [IQR: 16.1-110.5], whereas in those without, was 9.3 [6.5–11.7] (p < 0.0001). DISCUSSION The findings from this study emphasize that, in a significant number of cases, CT scans fell short in revealing the same level of tumor activity as observed in 68 Ga-PSMA PET-CT. This suggests that 68 Ga-PSMA PET-CT is a valuable modality for monitoring patients diagnosed with PCa, given the demonstrated inadequacy of tomography-based evidence alone, resulting in false negatives [ 14 ]. Furthermore, it was observed a significant elevation in SUVmax values in lungs with tomographic changes compared to those without such changes (Table 1 ). This implies an enhanced tracer uptake in the lungs, potentially indicative of a more advanced stage of the disease. Substantial evidence has shown that the SUVmax of the primary tumor could be used as a predictor of clinically significant prostate cancer [ 15 ]. In this study, the SUVmax values ​​were different from those reported in the literature, as several variables impact the SUVmax of 68 Ga-PSMA, encompassing its pharmacokinetic and pharmacodynamic aspects. These factors comprise the duration between the radiotracer administration and the examination, the calibration of the PET/CT equipment, and the radiation dosage. The presence of these variables adds complexity to the comparison of SUVmax across studies, creating challenges in standardizing comparisons (Table 1 ) [ 16 – 18 ]. In patients diagnosed and treated for localized PCa, many encounter distant recurrence, hinting at the presence of metastatic dissemination during the initial diagnosis. The conventional evaluation of tumor spread to soft tissues, especially the lymph nodes, relies on CT scans of the abdomen and pelvis. Detection of metastases often involves methods with limited precision, such as bone scintigraphy for bone metastases and CT for lesions in other regions [ 19 – 20 ]. The potential for an equivocal interpretation introduces a clinical challenge, necessitating supplementary imaging or histologic testing with an associated increase in costs. This additional diagnostic workup may also lead to delays in initiating curative treatment. The heightened diagnostic certainty frequency observed with 68 Ga-PSMA PET/CT represents a robust clinical advantage. [ 20 – 24 ]. Collectively, these findings suggest that, in patients with PCa who have already undergone 68 Ga-PSMA PET/CT, a CT scan may not be necessary for evaluating metastases. This equation assesses whether we are addressing our patients correctly during the follow-up, because when the tomographic evidence was found, most lesions were in different regions outside the prostate. In those cases where there was no tomographic evidence, the lesions were located only in the prostate, this occurred in 10 cases. Prospective studies have been conducted to assess the effectiveness of PSMA in PET compared to conventional imaging in the primary staging of patients with prostate cancer (PCa). In the short and medium term, finding that if metastatic disease were detected in the primary staging of high-risk prostate cancer (PCa), there would be more appropriate treatment for patients [ 14 ]. The PET CT has also been shown in other studies to be superior to plain bone scintigraphy for the detection of bone metastases [ 25 ]. In terms of diagnostic precision, the 68 Ga-PSMA PET/CT has demonstrated superior performance when comparing the same radioisotope against Magnetic Resonance Imaging (MRI) in the primary diagnosis of CaP in patients with PSA levels ranging between 4 and 20 ng/ml [ 15 ]. The systematic review by Eissa et al. demonstrated that 68 Ga-PSMA PET/CT showed proficiency in detecting recurrent lesions at diverse sites, including local recurrence, regional or distant lymph nodes, bone metastasis, as well as visceral or distant metastasis, even for small lesions [ 26 ]. The significance of employing 68Ga-PSMA extends to the pursuit of a diagnostic tool capable of categorizing patients through the identification and localization of lesions. This, in turn, contributes to the improvement of follow-up therapy for individuals experiencing recurrent disease post-radiotherapy [ 27 , 28 ]. The rising oncologic incidence worldwide creates a focus on early detection and treatment to improve prognosis. However, low- and middle-income countries are at a disproportionate disadvantage due to low availability and maldistribution of resources, which are many times scarce in public institutions [ 29 – 30 , 8 ]. This causes a disproportionate burden in their healthcare systems [ 5 , 31 ]. In Mexico, clinical practice guidelines advocate for the staging of tumors using MRI and categorizing them based on parameters such as anatomical extension, histological grade, molecular characteristics of the tumor, and serum levels of PSA; into low, intermediate, and high-risk groups, based in to aid in the evaluation of prognosis and treatment strategies. Specifically, for individuals with low-risk diseases, the guidelines discourage the use of imaging studies. In cases of intermediate risk, the recommendation leans towards employing either MRI or CT scans (focused on the abdomen and pelvis) to identify potential lymph node involvement or metastatic conditions. Meanwhile, for patients with high-risk diseases, the guidelines propose the utilization of CT scans (covering the chest, abdomen, and pelvis) along with bone scintigraphy [ 32 ]. The Mexican guidelines draw inspiration from international standards, particularly those set forth by the NICE (National Institute for Health and Care Excellence) and the ESMO (European Society for Medical Oncology). These global recommendations currently endorse the utilization of Technetium bone scans and thoracoabdominal CT scans, whole-body MRI, or PSMA PET CT for staging assessment in prostate cancer [ 33 – 34 , 6 ]. The findings from these studies prompt us to contemplate the potential future role of PET in either substituting conventional imaging for primary staging in high-risk diseases or serving as a diagnostic tool to alter the conventional research paradigm in prostate cancer. The main strengths of our study are related to the imaging modality used for the assessment of tumor burden in prostate cancer patients. 68 Ga-PSMA PET-CT is widely recognized for its high sensitivity and specificity and is considered a reference technique for early tumor detection. However, as in most retrospective imaging studies, histopathological confirmation of all lesions was not available. Although rare, false-negative or false-positive findings may occur, particularly in cases without histological verification. Therefore, the results should be interpreted in this context. This study has several additional limitations that should be acknowledged. Its retrospective design inherently introduces selection bias and limits the ability to establish causal relationships. Moreover, the heterogeneity of the patient population may restrict the generalizability of the findings. Reproducibility of PET/CT also remains a concern, as variations in imaging protocols and interpretation across centers may influence results. The use of low-dose CT, although advantageous in terms of radiation exposure, reduces sensitivity for detecting small lesions and may have contributed to the under-detection of disease. Finally, the absence of outcome data prevented us from assessing the clinical impact of the imaging findings on patient management and prognosis. Despite these limitations, our results add to the growing body of evidence supporting the role of PET, particularly ^68Ga-PSMA PET/CT, in prostate cancer staging. The proPSMA trial by Hofman et al. demonstrated the superiority of ^68Ga-PSMA PET/CT over conventional imaging with CT and bone scintigraphy, highlighting its potential to replace traditional modalities for primary staging in high-risk disease. These findings underscore the evolving role of ^68Ga-PSMA imaging and its promise to reshape diagnostic algorithms and research paradigms in prostate cancer. Further prospective research would be valuable to consolidate the role of 68Ga-PSMA PET-CT, as current evidence—including our study—predominantly comes from retrospective analyses of patients already diagnosed with the disease. CONCLUSIONS Tumoral activity detected with 68 Ga-PSMA PET-CT in the absence of tomographic evidence exhibited a lower uptake of a radiotracer measured by SUVmax, suggesting a potentially smaller tumoral volume indicative of early-stage lesions. These findings hold significant implications for middle- and low-income countries, such as Mexico, where PET-CT availability remains limited. It is imperative to conduct thorough evaluations encompassing histopathological correlations alongside 68 Ga-PSMA PET-CT imaging findings, both with and without CT findings. Declarations Conflicts of interest/Competing interests The authors declare that there are no conflicts of interest regarding the publication of this manuscript. Ethics Approval This study was approved by the Ethics Committee of the University Hospital José Eleuterio González (Approval Number: AH21-00024). All procedures were conducted in accordance with the ethical standards set by the institutional and national research committees, as well as the 1964 Declaration of Helsinki and its subsequent amendments, or other comparable ethical standards. Consent to participate Informed consent was not required since the information was collected during routine clinical care and the study was retrospective in nature. Consent for publication As this study was retrospective, informed consent for publication was not required. All personal data and identifying information were anonymized prior to analysis and publication. Funding This study was not funded by any external sources. The authors declare that no financial support was received for the conduct of the research or the preparation of the manuscript. Author Contribution L.A. A-L and E.V O-G, both authors contributed equally and should be considered in the position of first author. L.A A-L contributed to the conception and design of the study, and the drafting of the article. E.V. O-G contributed to the conception and design of the study, and the drafting of the article. M.C. H-S was involved in the analysis and interpretation of data. D. E-M contributed to the design of the study and the drafting of the article. M.E N-J contributed to the design of the study and the analysis of data. A. Q-G contributed to the drafting of the article and revising it critically for important intellectual content. R.E. E-O participated in the drafting of the article and the final approval of the version to be published. S. G-L was involved in revising the article critically for important intellectual content. G. E-R contributed to the design of the study and provided final approval of the version to be published. Data Availability The datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request. 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Lancet. 2020; 395(10231):1208-1216. doi: 10.1016/S0140-6736(20)30314-7. Pesec M, Sherertz T. Global health from a cancer care perspective. Future Oncol. 2015;11(15):2235-45. doi: 10.2217/fon.15.142. Franco, A., Shaker, M., Kalubi, D., & Hostettler, S. A review of sustainable energy access and technologies for healthcare facilities in the Global South. Sustainable Energy Technologies and Assessments. 2017; 22, 92-105. doi: 10.1016/j.seta.2017.02.022 Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Guías de Práctica Clínica (GPC). Instituto Mexicano del Seguro Social (IMSS). Diagnóstico y Tratamiento del cáncer de próstata. 2018; 140-18. Parker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, Tombal B, Gillessen S; ESMO Guidelines Committee. Electronic address: [email protected] . Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2020; 31(9):1119-1134. doi: 10.1016/j.annonc.2020.06.011. Huerta-Sanchez M, Hernandez-Alejo A, Gonzalez-Ballesteros A, Solis-Lara H; Low 68Ga-PSMA PET-CT uptake of tumoral lesions without tomographic changes in prostate cancer; Journal of the Mexican Federation of Radiology and Imaging; 0000-0002-3312-5673; b0000-0002-4510-0166. Additional Declarations No competing interests reported. Supplementary Files STROBEStatement.docx Cite Share Download PDF Status: Published Journal Publication published 07 Feb, 2026 Read the published version in SN Comprehensive Clinical Medicine → Version 1 posted Editorial decision: Revision requested 03 Oct, 2025 Reviews received at journal 02 Oct, 2025 Reviewers agreed at journal 24 Sep, 2025 Reviewers invited by journal 22 Sep, 2025 Editor assigned by journal 18 Sep, 2025 Submission checks completed at journal 18 Sep, 2025 First submitted to journal 17 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. 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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-7637504","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":523765944,"identity":"79ffc2ad-43b2-467d-a52f-358f347a3b15","order_by":0,"name":"Luis Adrian Alvarez-Lozada","email":"","orcid":"","institution":"Universidad Autónoma de Nuevo León","correspondingAuthor":false,"prefix":"","firstName":"Luis","middleName":"Adrian","lastName":"Alvarez-Lozada","suffix":""},{"id":523765948,"identity":"e39b2654-b6c0-4215-b1a8-c7b3f8477239","order_by":1,"name":"Ethel Valeria Orta-Guerra","email":"","orcid":"","institution":"Universidad 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1","display":"","copyAsset":false,"role":"figure","size":96621,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT study with 68Ga-PSMA in 64-year-old male with biochemical recurrence (APE 22.7 ng/mL) of prostate cancer with focal PSMA uptake in vertebral bodies of T2, T9 and T10, the highest uptake in T9 with SUVmax of 61.7 (a, b, c). a: Sagittal reformatting of a PET image; b. Sagittal bone reformatting of a computed tomography with no visible bone lesions; c. Sagittal reformatting of a PET-CT fusion. PET-CT study with 68Ga-PSMA in 68-year-old male with clinical suspicion of prostate cancer recurrence (APE 14.3 ng/mL), with multiple lesions in axial and appendicular skeleton, the highest uptake in sacrum with SUVmax of 111.1. (d, e, f) d: Sagittal reformatting of a PET image; e. Sagittal reformatting of a bone computed tomography; f. Sagittal reformatting of a PET-CT fusion\u003c/p\u003e","description":"","filename":"1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7637504/v1/88822e6d5defae361b98a618.jpg"},{"id":92735949,"identity":"44d7acdc-38cb-4009-b886-f4545c3b6139","added_by":"auto","created_at":"2025-10-03 16:32:44","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":88742,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT study with 68Ga-PSMA in a 69-year-old male with biochemical recurrence (PSA 0.67 ng/mL) of prostate cancer showing focal PSMA uptake in a normal-sized and morphologically normal left internal iliac lymph node, with SUVmax 26.8 (a, b, c); a: axial PET image; b: axial CT scan; c: axial PET-CT fusion. PET-CT study with 68Ga-PSMA in a 76-year-old male with biochemical recurrence (PSA 11.61 ng/mL) of prostate cancer showing focal PSMA uptake in a right phrenic lymphadenopathy with SUVmax 74.2; (d, e, f) d: axial PET image; e: axial CT scan; f: axial PET-CT fusion\u003c/p\u003e","description":"","filename":"2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7637504/v1/a599bbc8f1f9f38e6bcf9de4.jpg"},{"id":92735956,"identity":"18f5c1a9-9e15-4683-b3c4-b0489dd50c6d","added_by":"auto","created_at":"2025-10-03 16:32:44","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":132421,"visible":true,"origin":"","legend":"\u003cp\u003ePET-CT scan with 68Ga-PSMA in a 69-year-old male with biochemical recurrence (PSA 3.97 ng/mL) of prostate cancer showing focal PSMA uptake in the upper pole of the spleen, without a visible lesion on conventional CT, with SUVmax 15.9 (a, b, c); a: axial PET image; b: axial CT scan; c: axial PET-CT fusion. PET-CT scan with 68Ga-PSMA in a 72-year-old male with biochemical recurrence (PSA 41 ng/mL) of prostate cancer showing focal PSMA uptake in a nodule in the medial segment of the middle lobe of the lung with SUVmax 40.4 (d, e, f); d: axial PET image; e: axial CT scan; f: axial PET-CT fusion\u003c/p\u003e","description":"","filename":"3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7637504/v1/d7309c7c4096c2a436a71198.jpg"},{"id":102234289,"identity":"29917de6-c292-4755-84bc-956323fcebbb","added_by":"auto","created_at":"2026-02-09 16:09:18","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":954954,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7637504/v1/1e48ef7c-7119-41c2-b00d-1952f0fb4620.pdf"},{"id":92735947,"identity":"7a325aa9-3577-4811-81ad-337c82884f1a","added_by":"auto","created_at":"2025-10-03 16:32:44","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":21978,"visible":true,"origin":"","legend":"","description":"","filename":"STROBEStatement.docx","url":"https://assets-eu.researchsquare.com/files/rs-7637504/v1/7077afbb70fd07486f98dd11.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Comparative analysis of PSMA PET-CT: Assessing prostate cancer activity without CT findings","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eProstate cancer (PCa) ranks as the most prevalent neoplasm among men globally [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e], particularly in developed countries, correlating with advancing age [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In Mexico, its incidence in 2022 reached 39.1 per 100,000, establishing it as the predominant cancer in the male population [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Additionally, upon diagnosis, they are categorized as advanced with an unfavorable prognosis. Timely diagnosis and treatment are identified as the crucial factors associated with lower mortality rates in developed nations. When diagnosed with early screening, the 5-year survival rate nears 100%, in stark contrast to the 40% observed in developing countries. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. PCa can also affect transgender women, as the prostate is usually conserved after gender-confirming surgery, but it is not clear how common it is in this population. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eFurthermore, PCa represents a significant global health challenge, marked by numerous instances of biochemical relapse post-radical treatment. Hence, in cases of PCa recurrence, timely diagnosis becomes crucial for implementing effective rescue therapy [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe precision of \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT plays a pivotal role in identifying patients harboring occult distant metastatic disease, offering a valuable tool for developing personalized multimodal treatment strategies, particularly in the context of oligometastatic disease [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe SUVmax value demonstrates a correlation with the grade classification of prostate cancer [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e], thereby serving as a predictive indicator for the differentiation of tumoral tissue. Limited literature exists on the association between the uptake of the radiotracer \u003csup\u003e68\u003c/sup\u003eGa-PSMA in detecting tumor activity in PET-CT and its correlation with or without tomographic changes [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. This study aimed to examine the presence of tomographic evidence of prostate cancer lesions in patients exhibiting uptake of \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET CT.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cp\u003eThis cross-sectional study was conducted in the PET-CT Unit at the University Center of Radiology and Diagnostic Imaging of the Hospital Universitario \u0026ldquo;Dr. Jose E. Gonzalez\u0026rdquo; in Monterrey, Nuevo Leon, Mexico. Patients were included to evaluate primary prostate cancer with a \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT scan. Negative PET-CT results were excluded.\u003c/p\u003e\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy population and variables\u003c/h2\u003e\u003cp\u003eThe study variables were the determination of the maximum standardized uptake value (SUVmax), and the anatomic location of lesions detected by \u003csup\u003e68\u003c/sup\u003eGa-PSMA in bones, lymph nodes, prostate, and lungs. Imaging studies were classified as \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT positive with tomographic evidence or \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT positive without tomographic evidence.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eDefinitions\u003c/h3\u003e\n\u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT without tomographic evidence: radiotracer uptake by tumoral activity quantified by SUVmax and seen exclusively in the PET modality.\u003c/p\u003e\u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT with tomographic evidence: The radiotracer uptake in the PET modality was associated with structural changes according to RRECIST 1.1 criteria [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] due to tumor lesions identified in the CT modality.\u003c/p\u003e\u003cp\u003eIn \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT studies with two or more lesions in the same location variable (e.g. \u0026ldquo;lymph nodes\u0026rdquo;), the lesion with the highest uptake in each patient was selected based on the SUVmax at each anatomic site.\u003c/p\u003e\n\u003ch3\u003eImaging protocol\u003c/h3\u003e\n\u003cdiv class=\"Heading\"\u003eImaging protocol\u003c/div\u003e\u003cp\u003eAll patients underwent PET-CT on a Discovery Elite 690 system (GE Healthcare), which combines a high-resolution PET scanner with lutetium-yttrium oxyorthosilicate (LYSO) crystals and a 16-slice CT. The average administered activity of ^68Ga-PSMA was 1.8\u0026ndash;2.2 MBq/kg, and imaging acquisition was performed 60 minutes after intravenous injection. Patients received 1 L of water orally before the scan; in those with a history of prostatectomy, diluted non-ionic iodine contrast was administered orally with water.\u003c/p\u003e\u003cp\u003eThe CT acquisition was performed first, immediately before the PET scan, with the following technical parameters: tube potential 120 kV; mA automatically adjusted according to patient weight and height using the Care 2\u0026reg; application; pitch 0.75; rotation time 0.5 s; slice thickness 3 mm; slice interval 3 mm; and field of view (FOV) 500 mm. A diagnostic CT scan was obtained in the portal venous phase, 80 s after intravenous injection of iodinated contrast agent (Imeron 300).\u003c/p\u003e\u003cp\u003ePET images were then acquired in whole-body 3D mode (from skull base to mid-thigh), with two minutes per bed position. Reconstructions were performed using four iterations and 14 subsets, with an image matrix of 168 \u0026times; 168, Gaussian filter, and zoom value of 1. Attenuation and scatter correction were applied using the CT data.\u003c/p\u003e\u003cp\u003e\u003csup\u003e\u003cb\u003e68\u003c/b\u003e\u003c/sup\u003e\u003cb\u003eGa PSMA uptake analysis\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe PET-CT images were analyzed without blinding by a radiologist with experience of seven years in PET-CT and a radiology and imaging resident in training. SUVmax was determined using 2D regions of interest adjusted for size. In a PET, any focal uptake of \u003csup\u003e68\u003c/sup\u003eGa-PSMA higher than the surrounding background and not associated with physiologic uptake was considered indicative of malignancy. RECIST 1.1 criteria were followed to determine lesions suspicious for tumor activity on CT, including lymph nodes, bone, and lung [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e].\u003c/p\u003e\u003cdiv id=\"Sec6\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThe detection rate, defined as the number of studies with at least one tumor lesion, was divided into \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT with and without tomographic evidence and then plotted against SUVmax. Two-sided Mann-Whitney U tests were used to evaluate differences in SUVmax values between the groups with and without tomographic evidence. All tests were two-sided with a significant p-value of 0.05. The statistical analysis was performed using SPSS version 25. (IBM Corp. Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eEthical Considerations\u003c/h3\u003e\n\u003cp\u003e This study received prior review and approval from the corresponding Ethics and Research Committees, under registration number AH21-00024, ensuring compliance with the Helsinki Declaration as well as national and international research standards. The authors declare no financial or commercial gain from this study and have no conflicts of interest. All imaging studies utilized were not conducted specifically for this research. Informed consent was not required since the information was collected during routine clinical care and the study was retrospective in nature.\u003c/p\u003e"},{"header":"RESULTS","content":"\u003cp\u003eA total of 71 positive PET-CT studies from men diagnosed with prostate cancer were included, with a mean age of 64.9\u0026thinsp;\u0026plusmn;\u0026thinsp;7.5. From those studies, 113 lesions were identified, as some patients had lesions at two or more sites. There were 70 (61.9%) lesions with positive \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT without tomographic evidence and 43 (38.1%) with tomographic evidence. Tumoral activity was detected in the prostate (n 71, 62.8%), lymph nodes (n 17, 15%), bone (n 14, 12.4%), and lungs(n 11, 9.7%). (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\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\u003eComparison between lesions detected by 68Ga-PSMA PET-CT with and without tomographic evidence.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\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\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"8\" nameend=\"c9\" namest=\"c2\"\u003e\u003cp\u003eLesions detected by \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eWith CT changes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u003cp\u003eWithout CT changes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c8\" namest=\"c7\"\u003e\u003cp\u003e\u003cem\u003ep-value\u003c/em\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003eSUVmax\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003eN (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003eSUVmax\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eOverall lesions\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43 (38)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e18.4 [8.7\u0026ndash;34.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e70 (62)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e8 [4.8\u0026ndash;14.9]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.001*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eBone\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12 (27.9)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e24.3 [9-48.5]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2 (2.8)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e4.7 [4.5\u0026ndash;4.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.144\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLymph nodes\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e13 (30.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e17.2 [6.5\u0026ndash;50.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e7.7 [5.4\u0026ndash;8.7]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.113\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eProstate and prostatic bed\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e11 (25.6)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e14.7 [9.9\u0026ndash;18.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e60 (86.1)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e11.7 [6.2\u0026ndash;20]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e0.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eLungs\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e7 (16.3)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c4\" namest=\"c3\"\u003e\u003cp\u003e30.7 [14.6\u0026ndash;52.4]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4 (5.5)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c7\" namest=\"c6\"\u003e\u003cp\u003e4.3 [2.2\u0026ndash;7.8]\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"2\" nameend=\"c9\" namest=\"c8\"\u003e\u003cp\u003e\u003cb\u003e0.008*\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eCT \u0026ndash; Computed Tomography. Data is presented as frequencies and percentages in parentheses or median and interquartile range in brackets. The overall lesion value was calculated as the mean SUVmax of the presented lesions or as the SUVmax of a single lesion if only one was present. Mann-Whitney Test was used to compare SUVmax between those with and without tomographic evidence.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eW-With; WO \u0026ndash; Without; CT \u0026ndash; Computed Tomography. *p\u0026thinsp;\u0026lt;\u0026thinsp;0.05\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eProstate lesions most frequently lacked tomographic evidence in comparison to the other lesions (n\u0026thinsp;=\u0026thinsp;60/70, 86%). In the group with tomographic evidence, the frequency of lesions was homogeneous, although lungs\u0026rsquo; lesions were less frequent than the rest. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, \u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e,\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT uptake was similar between all those lesions with and without tomographic evidence. Lungs were the exception, in which SUVmax was significantly higher whenever there was tomographic evidence of lesions (MD\u0026thinsp;=\u0026thinsp;29.9; 95% CI\u0026thinsp;=\u0026thinsp;8.3\u0026ndash;51.6; p-value\u0026thinsp;=\u0026thinsp;0.008) (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThere were 68 out of 71 (95.7%) patients with PSA value available, with a wide range of 1.3 ng/mL to 665 ng/mL. The median PSA was 11.7 [IQR: 8-24.7] ng/mL. In patients with tomographic evidence of lesions, there was a PSA median of 27.6 [IQR: 16.1-110.5], whereas in those without, was 9.3 [6.5\u0026ndash;11.7] (p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThe findings from this study emphasize that, in a significant number of cases, CT scans fell short in revealing the same level of tumor activity as observed in \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT. This suggests that \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT is a valuable modality for monitoring patients diagnosed with PCa, given the demonstrated inadequacy of tomography-based evidence alone, resulting in false negatives [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eFurthermore, it was observed a significant elevation in SUVmax values in lungs with tomographic changes compared to those without such changes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). This implies an enhanced tracer uptake in the lungs, potentially indicative of a more advanced stage of the disease. Substantial evidence has shown that the SUVmax of the primary tumor could be used as a predictor of clinically significant prostate cancer [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn this study, the SUVmax values ​​were different from those reported in the literature, as several variables impact the SUVmax of \u003csup\u003e68\u003c/sup\u003eGa-PSMA, encompassing its pharmacokinetic and pharmacodynamic aspects. These factors comprise the duration between the radiotracer administration and the examination, the calibration of the PET/CT equipment, and the radiation dosage. The presence of these variables adds complexity to the comparison of SUVmax across studies, creating challenges in standardizing comparisons (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) [\u003cspan additionalcitationids=\"CR17\" citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eIn patients diagnosed and treated for localized PCa, many encounter distant recurrence, hinting at the presence of metastatic dissemination during the initial diagnosis. The conventional evaluation of tumor spread to soft tissues, especially the lymph nodes, relies on CT scans of the abdomen and pelvis. Detection of metastases often involves methods with limited precision, such as bone scintigraphy for bone metastases and CT for lesions in other regions [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe potential for an equivocal interpretation introduces a clinical challenge, necessitating supplementary imaging or histologic testing with an associated increase in costs. This additional diagnostic workup may also lead to delays in initiating curative treatment. The heightened diagnostic certainty frequency observed with \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET/CT represents a robust clinical advantage. [\u003cspan additionalcitationids=\"CR21 CR22 CR23\" citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eCollectively, these findings suggest that, in patients with PCa who have already undergone \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET/CT, a CT scan may not be necessary for evaluating metastases. This equation assesses whether we are addressing our patients correctly during the follow-up, because when the tomographic evidence was found, most lesions were in different regions outside the prostate. In those cases where there was no tomographic evidence, the lesions were located only in the prostate, this occurred in 10 cases.\u003c/p\u003e\u003cp\u003eProspective studies have been conducted to assess the effectiveness of PSMA in PET compared to conventional imaging in the primary staging of patients with prostate cancer (PCa). In the short and medium term, finding that if metastatic disease were detected in the primary staging of high-risk prostate cancer (PCa), there would be more appropriate treatment for patients [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e]. The PET CT has also been shown in other studies to be superior to plain bone scintigraphy for the detection of bone metastases [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. In terms of diagnostic precision, the \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET/CT has demonstrated superior performance when comparing the same radioisotope against Magnetic Resonance Imaging (MRI) in the primary diagnosis of CaP in patients with PSA levels ranging between 4 and 20 ng/ml [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe systematic review by Eissa et al. demonstrated that \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET/CT showed proficiency in detecting recurrent lesions at diverse sites, including local recurrence, regional or distant lymph nodes, bone metastasis, as well as visceral or distant metastasis, even for small lesions [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. The significance of employing 68Ga-PSMA extends to the pursuit of a diagnostic tool capable of categorizing patients through the identification and localization of lesions. This, in turn, contributes to the improvement of follow-up therapy for individuals experiencing recurrent disease post-radiotherapy [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e, \u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe rising oncologic incidence worldwide creates a focus on early detection and treatment to improve prognosis. However, low- and middle-income countries are at a disproportionate disadvantage due to low availability and maldistribution of resources, which are many times scarce in public institutions [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. This causes a disproportionate burden in their healthcare systems [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]. In Mexico, clinical practice guidelines advocate for the staging of tumors using MRI and categorizing them based on parameters such as anatomical extension, histological grade, molecular characteristics of the tumor, and serum levels of PSA; into low, intermediate, and high-risk groups, based in to aid in the evaluation of prognosis and treatment strategies. Specifically, for individuals with low-risk diseases, the guidelines discourage the use of imaging studies. In cases of intermediate risk, the recommendation leans towards employing either MRI or CT scans (focused on the abdomen and pelvis) to identify potential lymph node involvement or metastatic conditions. Meanwhile, for patients with high-risk diseases, the guidelines propose the utilization of CT scans (covering the chest, abdomen, and pelvis) along with bone scintigraphy [\u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e]. The Mexican guidelines draw inspiration from international standards, particularly those set forth by the NICE (National Institute for Health and Care Excellence) and the ESMO (European Society for Medical Oncology). These global recommendations currently endorse the utilization of Technetium bone scans and thoracoabdominal CT scans, whole-body MRI, or PSMA PET CT for staging assessment in prostate cancer [\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e\u003cp\u003eThe findings from these studies prompt us to contemplate the potential future role of PET in either substituting conventional imaging for primary staging in high-risk diseases or serving as a diagnostic tool to alter the conventional research paradigm in prostate cancer.\u003c/p\u003e\u003cp\u003eThe main strengths of our study are related to the imaging modality used for the assessment of tumor burden in prostate cancer patients. \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT is widely recognized for its high sensitivity and specificity and is considered a reference technique for early tumor detection. However, as in most retrospective imaging studies, histopathological confirmation of all lesions was not available. Although rare, false-negative or false-positive findings may occur, particularly in cases without histological verification. Therefore, the results should be interpreted in this context.\u003c/p\u003e\u003cp\u003eThis study has several additional limitations that should be acknowledged. Its retrospective design inherently introduces selection bias and limits the ability to establish causal relationships. Moreover, the heterogeneity of the patient population may restrict the generalizability of the findings. Reproducibility of PET/CT also remains a concern, as variations in imaging protocols and interpretation across centers may influence results. The use of low-dose CT, although advantageous in terms of radiation exposure, reduces sensitivity for detecting small lesions and may have contributed to the under-detection of disease. Finally, the absence of outcome data prevented us from assessing the clinical impact of the imaging findings on patient management and prognosis.\u003c/p\u003e\u003cp\u003eDespite these limitations, our results add to the growing body of evidence supporting the role of PET, particularly ^68Ga-PSMA PET/CT, in prostate cancer staging. The proPSMA trial by Hofman et al. demonstrated the superiority of ^68Ga-PSMA PET/CT over conventional imaging with CT and bone scintigraphy, highlighting its potential to replace traditional modalities for primary staging in high-risk disease. These findings underscore the evolving role of ^68Ga-PSMA imaging and its promise to reshape diagnostic algorithms and research paradigms in prostate cancer. Further prospective research would be valuable to consolidate the role of 68Ga-PSMA PET-CT, as current evidence\u0026mdash;including our study\u0026mdash;predominantly comes from retrospective analyses of patients already diagnosed with the disease.\u003c/p\u003e"},{"header":"CONCLUSIONS","content":"\u003cp\u003eTumoral activity detected with \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT in the absence of tomographic evidence exhibited a lower uptake of a radiotracer measured by SUVmax, suggesting a potentially smaller tumoral volume indicative of early-stage lesions. These findings hold significant implications for middle- and low-income countries, such as Mexico, where PET-CT availability remains limited. It is imperative to conduct thorough evaluations encompassing histopathological correlations alongside \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT imaging findings, both with and without CT findings.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003ch2\u003eConflicts of interest/Competing interests\u003c/h2\u003e\u003cp\u003eThe authors declare that there are no conflicts of interest regarding the publication of this manuscript.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eEthics Approval\u003c/strong\u003e\u003cp\u003e This study was approved by the Ethics Committee of the University Hospital Jos\u0026eacute; Eleuterio Gonz\u0026aacute;lez (Approval Number: AH21-00024). All procedures were conducted in accordance with the ethical standards set by the institutional and national research committees, as well as the 1964 Declaration of Helsinki and its subsequent amendments, or other comparable ethical standards.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent to participate\u003c/strong\u003e\u003cp\u003eInformed consent was not required since the information was collected during routine clinical care and the study was retrospective in nature.\u003c/p\u003e\u003c/p\u003e\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003cp\u003e As this study was retrospective, informed consent for publication was not required. All personal data and identifying information were anonymized prior to analysis and publication.\u003c/p\u003e\u003ch2\u003eFunding\u003c/h2\u003e\u003cp\u003eThis study was not funded by any external sources. The authors declare that no financial support was received for the conduct of the research or the preparation of the manuscript.\u003c/p\u003e\u003ch2\u003eAuthor Contribution\u003c/h2\u003e\u003cp\u003eL.A. A-L and E.V O-G, both authors contributed equally and should be considered in the position of first author. L.A A-L contributed to the conception and design of the study, and the drafting of the article. E.V. O-G contributed to the conception and design of the study, and the drafting of the article. M.C. H-S was involved in the analysis and interpretation of data. D. E-M contributed to the design of the study and the drafting of the article. M.E N-J contributed to the design of the study and the analysis of data. A. Q-G contributed to the drafting of the article and revising it critically for important intellectual content. R.E. E-O participated in the drafting of the article and the final approval of the version to be published. S. G-L was involved in revising the article critically for important intellectual content. G. E-R contributed to the design of the study and provided final approval of the version to be published.\u003c/p\u003e\u003ch2\u003eData Availability\u003c/h2\u003e\u003cp\u003eThe datasets generated and/or analyzed during the current study are available from the corresponding author upon reasonable request.\u003c/p\u003e"},{"header":"References","content":"\u003col class=\"decimal_type\"\u003e\n\u003cli\u003eSiegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics. CA Cancer J Clin. 2022; 72(1):7-33. doi: 10.3322/caac.21708.\u003c/li\u003e\n\u003cli\u003eSekhoacha M, Riet K, Motloung P, Gumenku L, Adegoke A, Mashele S. Prostate Cancer Review: Genetics, Diagnosis, Treatment Options, and Alternative Approaches. Molecules, 2022 ; 27(17):5730. doi: 10.3390/molecules27175730. \u003c/li\u003e\n\u003cli\u003ePernar CH, Ebot EM, Wilson KM, Mucci LA. The Epidemiology of Prostate Cancer. 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CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834.\u003c/li\u003e\n\u003cli\u003eGu\u0026iacute;as de Pr\u0026aacute;ctica Cl\u0026iacute;nica (GPC). Instituto Mexicano del Seguro Social (IMSS). Diagn\u0026oacute;stico y Tratamiento del c\u0026aacute;ncer de pr\u0026oacute;stata. 2018; 140-18.\u003c/li\u003e\n\u003cli\u003eParker C, Castro E, Fizazi K, Heidenreich A, Ost P, Procopio G, Tombal B, Gillessen S; ESMO Guidelines Committee. Electronic address: [email protected]. Prostate cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment, and follow-up. Ann Oncol. 2020; 31(9):1119-1134. doi: 10.1016/j.annonc.2020.06.011.\u003c/li\u003e\n\u003cli\u003eHuerta-Sanchez M, Hernandez-Alejo A, Gonzalez-Ballesteros A, Solis-Lara H; Low 68Ga-PSMA PET-CT uptake of tumoral lesions without tomographic changes in prostate cancer; Journal of the Mexican Federation of Radiology and Imaging; 0000-0002-3312-5673; b0000-0002-4510-0166.\u003c/li\u003e\n\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":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"Diagnostic precision, Staging, PET-TC, Prostate Cancer, PSMA","lastPublishedDoi":"10.21203/rs.3.rs-7637504/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7637504/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBACKGROUND/OBJECTIVE:\u003c/h2\u003e\u003cp\u003eProstate cancer (PCa) is a prevalent malignancy globally, especially in developed nations. Timely diagnosis and treatment are crucial for survival, with higher rates in developed countries. \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT aids in identifying metastatic disease, guiding personalized treatment strategies. The aim of this study is to compare the uptake of the radiotracer \u003csup\u003e68\u003c/sup\u003eGa-PSMA in primary and metastatic prostate cancer lesions identified on PSMA PET-CT against conventional CT (Computed Tomography) in staging prostate cancer patients.\u003c/p\u003e\u003ch2\u003eMETHODS\u003c/h2\u003e\u003cp\u003eA retrospective, cross-sectional study was conducted in the PET-CT Unit. Seventy-one patients diagnosed with prostate cancer by histopathology who underwent PSMA PET-CT scan and who were referred for CT staging were included. The study variables were the determination of the maximum standardized uptake value (SUVmax), and the anatomic location of lesions detected by \u003csup\u003e68\u003c/sup\u003eGa-PSMA in bone, lymph node, prostate, and lung. Lesions were classified as seen by PSMA PET-CT or by both PSMA PET-CT and conventional Computed Tomography.\u003c/p\u003e\u003ch2\u003eRESULTS\u003c/h2\u003e\u003cp\u003eA total of 113 lesions of tumoral activity were identified: 70 lesions were detected only with \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT with a mean SUVmax of 14.14\u0026thinsp;\u0026plusmn;\u0026thinsp;11.25, in contrast to a mean SUVmax of 23.15\u0026thinsp;\u0026plusmn;\u0026thinsp;20.51 in 43 lesions detected by both PSMA PET-CT and conventional CT. (p\u0026thinsp;=\u0026thinsp;0.049).\u003c/p\u003e\u003ch2\u003eCONCLUSION\u003c/h2\u003e\u003cp\u003ePositive \u003csup\u003e68\u003c/sup\u003eGa-PSMA PET-CT showed metastatic disease that otherwise would have not been diagnosed in patients undergoing conventional CT, which corresponds to an upstaging in 67% of patients. These results are relevant due to the limited availability of PET-CT equipment in global south countries.\u003c/p\u003e","manuscriptTitle":"Comparative analysis of PSMA PET-CT: Assessing prostate cancer activity without CT findings","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-10-03 16:32:39","doi":"10.21203/rs.3.rs-7637504/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2025-10-03T22:12:36+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-10-02T05:31:09+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"44767476048650963811020491680605522780","date":"2025-09-24T09:52:22+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-09-22T10:58:16+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-18T11:24:06+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-18T09:55:54+00:00","index":"","fulltext":""},{"type":"submitted","content":"SN Comprehensive Clinical Medicine","date":"2025-09-17T08:05:58+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"sn-comprehensive-clinical-medicine","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"sncm","sideBox":"Learn more about [SN Comprehensive Clinical Medicine](https://www.springer.com/journal/42399)","snPcode":"42399","submissionUrl":"https://submission.nature.com/new-submission/42399/3","title":"SN Comprehensive Clinical Medicine","twitterHandle":"","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"stoa","reportingPortfolio":"Springer Hybrid","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"ced500c4-1fcc-4236-b849-6e4261501a65","owner":[],"postedDate":"October 3rd, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2026-02-09T16:06:29+00:00","versionOfRecord":{"articleIdentity":"rs-7637504","link":"https://doi.org/10.1007/s42399-025-02246-y","journal":{"identity":"sn-comprehensive-clinical-medicine","isVorOnly":false,"title":"SN Comprehensive Clinical Medicine"},"publishedOn":"2026-02-07 15:57:34","publishedOnDateReadable":"February 7th, 2026"},"versionCreatedAt":"2025-10-03 16:32:39","video":"","vorDoi":"10.1007/s42399-025-02246-y","vorDoiUrl":"https://doi.org/10.1007/s42399-025-02246-y","workflowStages":[]},"version":"v1","identity":"rs-7637504","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7637504","identity":"rs-7637504","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}