Assessing Germline Genetic Testing Patterns, Awareness, and Adherence to Guidelines Among Lebanese Prostate Cancer Patients

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Despite poor prognosis for metastatic cases, treatment advances have extended survival. However, data on germline genetic testing in Lebanese prostate cancer patients is scarce. This study investigates the frequency and role of genetic testing in prostate cancer management in Lebanon, focusing on its impact on treatment decisions. Methods Pathogenic variant status was assessed using an NGS panel. Data from the Saint Joseph University genetic lab (2013–2022) was analyzed, including demographics, diagnosis year, testing dates, and treatment outcomes. Referral patterns between oncologists and urologists were compared, and the use of PARP inhibitors was discussed. Results Only 20 patients were referred for genetic testing over 12 years. Our study's low referral rates reflect real-world data from a third-country setting. Among these, 15% were referred by urologists and 85% by oncologists. Of those tested, 20% were positive, two with BRCA2 mutations and two with MSH2 variants. Testing was mostly done after disease progression or metastasis, four were referred due to family history. None of the positive patients received PARP inhibitors. Conclusion The study revealed low genetic testing referral rates, consistent with global trends despite updated guidelines. Contributing factors include complex guidelines, limited provider awareness, and high testing costs. Interestingly, these factors are more pronounced in the context of our study. Improved education, clearer guidelines, and telemedicine access could boost genetic testing uptake, enhancing prostate cancer treatment standards and survival rates locally and globally, with a particular focus on developing countries including Lebanon. Prostate cancer genetic testing HRD germline variants hereditary personalized treatment Lebanon Introduction Prostate cancer stands as the most prevalent cancer among men globally and specifically in Lebanon. It is also known to be the second most deadly after lung cancer ( 1 )( 2 ). The age-standardized incidence rate of prostate cancer in Lebanon has exhibited a noteworthy increase from 29.1 per 100,000 in 2005 to 37.3 per 100,000 in 2016, surpassing the global average incidence rate in 2012. This incidence is highly dependent on screening practices involving prostate-specific antigen (PSA) and the number of PSA-driven biopsies ( 2 ). The median overall survival for metastatic prostate cancer has traditionally ranged from 18 to 36 months. However, recent clinical trials such as PEACE-1 and ARASENS have demonstrated that patients with advanced prostate cancer can achieve median survival rates exceeding 36 months, with some reaching over 5 years. This improvement is likely attributed to the combined benefits of new antiandrogens and subsequent treatments, including PARP inhibitors The median overall survival (OS) for metastatic prostate cancer has traditionnaly ranged from 18 to 36 months ( 3 ). However, recent clinical trials such as PEACE-1 and ARASENS have demonstrated that patients with advanced prostate cancer can achieve median survival rates exceeding 36 months, with some reaching over 5 years ( 4 )( 5 ). This improvement is likely attributed to the combined benefits of new antiandrogens and subsequents treatments. In the process of cancer progression, cancer cells are prone to defects in DNA repair and evolve to an aggressive phenotype ( 6 ). DNA damage response (DDR) pathway is implicated in maintaining genomic stability. Any defect or pathogenic variant in a gene implicated in this pathway can lead to prostate cancer ( 7 , 8 , 9 ). DDR germline or somatic alterations are found in 23% of metastatic prostate cancer according to the International Stand Up to Cancer/Prostate Cancer Foundation/American Association for Cancer Research Prostate Cancer Team ( 10 ). The BReast CAncer gene 2 ( BRCA2) , which is the most mutated gene in prostate cancer, functions as a tumor suppressor gene, playing a pivotal role in the DNA repair mechanism by regulating homologous recombination (HR). Moreover, it has been demonstrated that these pathogenic variants increase the risk of prostate cancer with an estimation of 15% by the age of 65 ( 11 ). Later, other studies demonstrated that mutated BRCA2 was correlated with more advanced stage, high grade and poorer survival ( 12 , 13 , 14 ). There is also evidence of multiple other mutated genes, such as ATM 1.6%, CHEK2 1.9%, BRCA1 0.9%, RAD51D 0.4%, and PALB2 0.4% ( 15 , 16 ). Nowadays, BRCA testing is usually done in breast, ovarian and other hereditary cancers, but there is less consensus regarding testing in prostate cancer. According to a recent review guidelines and consensus, genetic testing is offered in men with metastatic disease, but less clear consensus was found in men with localized disease due to its higher incidence in patients with metastases ( 17 , 18 ). Metastatic prostate or recurrent prostate cancer progresses through various stages, initially starting as castration-sensitive (mCSPC), where androgen deprivation therapy proves highly effective. However, as the disease advances, it transitions to a castration-resistant stage (mCRPC). Despite the continued use of androgen deprivation therapy, new generation anti-androgen therapy and Taxane chemotherapy, the efficacy diminishes, leading to a limited range of treatment options. Indeed, castration-resistant stage poses significant challenges ( 19 ). Many studies have been conducted on the use of genetic testing to guide treatment options for metastatic patients, yielding promising results, particularly through the inhibition of poly (ADP-ribose) polymerase (PARP) enzymes in patients with a pathogenic variant in BRCA or other homologous recombination deficiency (HRD) genes. Considering these advancements, genetic testing, mainly by NGS panels, has become essential, not only for assessing hereditary transmission but also as a valuable tool in therapeutic decision-making. However, various factors may influence the frequency of requested molecular tests, particularly in countries with less stringent regulations and continuous economic crisis, such as Lebanon. In Lebanon, genetic cancer risk assessment is mainly managed by the treating physician, to identify eligible patients and provide necessary information before referring them for genetic testing. In the current study, we investigate the adherence to genetic testing recommendations in Lebanese patients with prostate cancer and assess its impact on guiding treatment decisions in clinical practice. Materials and methods Data from prostate cancer patients referred for genetic testing between 2013 and January 2025 was collected from the Center Jacques Loiselet for medical genetics and genomics (CGGM), at the faculty of medicine, Saint Joseph University of Beirut (USJ), Lebanon. This retrospective study was approved by the ethical committee at Saint Joseph University of Beirut and Hotel Dieu de France, Lebanon. Genetic testing was performed on peripheral blood samples from the patients to screen for germline variants in a panel of genes by Next Generation Sequencing (NGS). After preparation, the final indexed libraries were sequenced on an Illumina platform. In this analysis, the following regions were targeted: coding regions of the panel genes, 10 bp of flanking intronic sequences, and known pathogenic/likely pathogenic variants within these genes included in the enrichment design. The analyzed genes are the following: APC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, DIS3L2, EPCAM, FANCC, FH, FLCN, GALNT12, HOXB13, KIT, MC1R,MEN1, MET, MITF, MLH1, MLH3, MRE11, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PMS2, POLD1, POLE, POT1, PRSS1, PTCH1, PTEN, RAD50, RAD51C, RAD51D,RECQL, RET, RNF43, RPS20, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, TP53, TSC1, TSC2, VHL, WT1, XRCC2 and XRCC3. Additionally, patients’ data were collected from the laboratory and physician’s clinic, including demographics data, the year of diagnosis, metastatic stage, molecular testing date, and molecular results. Also, the specialty of the referring physician was recorded distinguishing between oncologists and urologists. Patients were subsequently classified as either “positive” or “negative”. For those identified as positive, we contacted their physicians to determine whether PARP inhibitor therapy had been prescribed. This analysis aimed to evaluate the impact of genetic status on treatment decisions. Ultimately, the aim was to provide insights into the clinical utility of genetic testing in managing prostate cancer, particularly in a developing country like Lebanon, where medical and financial resources are limited. Results In our study, only twenty prostate cancer patients were referred to our center (CGGM) for genetic testing by NGS, over a period of 12 years. Our center is a leading tertiary reference center in Lebanon and one of the largest and most reputable in the country. Data of these 20 patients were collected. The patient cohort exhibited diverse characteristics, which are summarized in Table 1 . The median age was 66 years, ranging between 47 and 77 years. The median age at diagnosis was sixty. In two of our patients (#13 and #14), a diagnosis of prostate cancer was made but no data was available regarding the time and age at diagnosis and their gleason score. Among the referrals, 15% were made by urologists, while the majority (85%) was referred by the oncologists ( Table 1 ). Interestingly, none of the patients were referred at the time of diagnosis. Instead, patients experienced an average delay of at least 3 years before being referred for genetic testing. Referrals primarily occurred due to disease progression, including metastasis or the development of CRPC. Only four patients were considered metastatic castration sensitive. Table 1 Cohort characteristics and results Patient Diagnosis year Age at diagnosis Gleason Score Metastasis Date of diagnosis Treatment of HSPC Date of castration resistan ce Treatment of CRPC Year of genetic testing Referring physician Reason for referral Genetic Test result Use of PARP inhibit ors 1 2016 67 G7 2016 - pelvic nodes and bones LHRH agonist (Leuprolide) + Chemotherapy (Docetaxel) 2019 2019: ARB (Enzalutamide) 2021: Chemotherapy (Cabazitaxel) + LHRH Agonist (Gosereline) 2023 Oncologist Disease progression - No 2 2023 75 G9 2023 pulmonary and bones LHRH agonist (Gosereline) + ARB (Bicalutamide) → Chemotherapy (Docetaxel) + Abiraterone non CRPC NA 2023 Oncologist Disease progression - No 3 2022 52 G9 2022 bones LHRH agonist (Gosereline) + ARB (Bicalutamide) + Chemotherapy (Docetaxel) non CRPC NA 2024 Oncologist Regular testing - No 4 2009 62 G8 2018 - pelvic lymph nodes Surgical 2009 2014 2014: LHRH antagonist + ARB (Enzalutamide) 2022: Chemotherapy (Cabazitaxel) 2022 Oncologist Disease progression - No 5 2016 58 G8 2020 - bones Surgical + radiotherapy 2020 Chemotherapy (Docetaxel◊ Cabazitaxel) 2021 Oncologist Disease progression - No 6 2016 68 G8 NA Hormonotherapy + Radiotherapy 2017 2019 Abiraterone + Chemotherapy (Docetaxel) 2021 Oncologist Disease progression - No 7 2012 62 G8 2018 X X X 2019 Oncologist X - No 8 2019 85 Not determ ined on biopsy 2019 - nodes and bones Surgical + Abiraterone 2020 Chemotherapy (Docetaxel) 2020 Oncologist Disease progression - No 9 Not diagnosed NA NA NA NA NA NA 2020 Oncologist Family history BRCA2 + No 10 2020 43 G6 Not metastatic Hormonotherapy + radiotherapy Non CRPC NA 2020 Urologist Family history BRCA2 + No 11 2010 53 G8 2017 bones − 2021 hepatic Surgical → LHRH agonist (Gosereline) + ARB (Bicalutamide) 2017 2017: LHRH agonist (Gosereline)+ ARB (Enzalu amide) 2019: LHRH agonist (Gosereline) + Chemotherapy (Cabazitaxel) + Abiraterone 2021: Chemotherapy (Docetaxel + Carboplatine) 2021 Oncologist CRPC - No 12 2010 53 G8 2010- Pelvic lymph nodes Surgical + LHRH antagonist 2017 2017: LHRH agonist (Gosereline) + Chemotherapy (Docetaxel) 2018: LHRH agonist (Gosereline) + chemotherapy (Cabazitaxel) 2020: Abiraterone + ARB (Enzalutamide) 2021 Oncologist Disease progression - No 13 Not Diagnosed NA NA NA NA NA NA 2018 Oncologist Family History - NA 14 Not diagnosed NA NA NA NA NA NA 2020 Oncologist Family History - NA 15 2017 58 G8 Bones Orchidectomy + Chemotherapy (Taxotere) 2017 Chemotherapy (Cabazitaxel) + Bone radiotherapy 2018 Oncologist Disease progression MSH2 + No 16 2019 61 G9 Bones LHRHagonist (Gosereline) + Pelvic irradiation 2020 2019: LHRH agonist (Gosereline) + ARB (Enzalutamide) 2020: Chemotherapy (Cabazitaxel) 2021 Oncologist Disease progression MSH2 + No 17 2016 69 G9 Hepatic LHRH agonist (Gosereline) + Chemotherapy (Docetaxel) 2016 2016: ARB (Enzalutamide) 2019: Chemotherapy (Cabazitaxel) 2023 Oncologist Disease progression - No 18 2010 62 G7 2022 - pulmonary and bones 2011: Radiotherapy + LHRH agonist (Gosereline) 2022: LHRH agonist (Gosereline) + Bicalutamide 2022 2022: LHRH agonist (Gosereline) + ARB (Apalutamide) 2024: Chemotherapy (Docetaxel◊ Cabazitaxel) 2023 Urologist Disease progression - No 19 2024 50 G6 Non metastatic Treatment not started yet NA NA 2024 Urologist At diagnosis - No 20 2020 49 G9 Bone metastases LHRH agonist (Gosereline) + Abiraterone + Chemotherapy (Docetaxel) Radiotherapy Non CRPC NA 2024 Oncologist Disease progression - No LHRH:luteinizing hormone-releasing hormone; ARB: Androgen receptor blocker; BRCA: BReast CAncer gene; G:Grade; CRPC: castration-resistant prostate cancer; NA: Not Available; +: Positive ; -: Negative; à: Then Out of the twenty patients tested, only four (20%) tested positive. Among these four cases, two unrelated patients showed the same pathogenic variant in the BRCA2 gene, and the other two patients showed two different variants in MSH2 . The list of these variants and their classification are represented in Table 2 . Interestingly, four of our patients who tested positive were referred initially for genetic counseling regarding a family history of prostate cancer, one had a localized disease, and the three others didn’t develop prostate cancer. Three patients presented confirmed pathogenic germline variants, while only one MSH2 variant was classified as Variant of Uncertain Significance (VUS). Intriguingly, none of the four patients with positive germline findings, initiated treatment with PARP inhibitors. Table 2 The identified variants in 4 Lebanese prostate cancer patients Patient Gene Variant Classification (according to ClinVar) 9 BRCA2 c.6308C > A, p.(Ser2103 *) Pathogenic 10 BRCA2 c.6308C > A, p.(Ser2103 *) Pathogenic 15 MSH2 c.1331G > T, p.(Arg444Leu) Conflicting interpretations of pathogenicity, VUS 16 MSH2 c.1552_1553del, p.(Gln518Valfs*10) Pathogenic Discussion In this study, we report for the first on the molecular spectrum of prostate cancer patients in Lebanon. Such data are scarce and not available in the medical literature. Our study found pathogenic variants in the HRD gene among the four positive cases (20%). We found 10% BRCA2 -positive and 10% MSH2 -positive cases, aligning with worldwide data indicating that HRD alterations are the most prevalent in prostate cancer patients ( 18 ). Pritchard et al. reported a substantial incidence of germline pathogenic variants in BRCA2 in advanced prostate cancer cases, which was corroborated by Robinson et al. 's findings of both somatic and germline BRCA2 alterations in metastatic prostate cancer ( 10 , 15 ). Furthermore, a broader study in men with early and advanced prostate cancer reaffirmed the frequency of pathogenic variants in the DNA repair genes. The most common mutated genes were BRCA2 and ATM , followed by MSH6 and MSH2 ( 20 ). These collective findings, and our study, underscore germline pathogenic variants in BRCA2 as the most prevalent and clinically significant in prostate cancer. Our study clearly demonstrates that genetic testing referrals for prostate cancer cases are low, as we have identified only 20 referrals out of all the prostate cancer cases from 2013 till 2025. This aligns with international reports showing that genetic testing for prostate cancer is still low. Following the 2017 National Comprehensive Cancer Network® (NCCN®) guidelines, which advocate for germline testing of DNA repair genes in all men with high- or very-high-risk clinically localized prostate cancer and metastatic prostate cancer (NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Prostate Cancer V.2.2017), there has been a noted increase in homologous recombination repair (HRR) gene testing. Despite this uptick, the overall testing rates have remained low at around 13% ( 21 ). Nowadays, following the 2024 version of NCCN guidelines, it is recommended to perform germline genetic testing for patients with prostate cancer and a suggestive family history or high-risk, very-high-risk, regional, or metastatic prostate cancer regardless of family history, Ashkenazi Jewish ancestry or a personal history of breast cancer. In addition, germline genetic testing should be considered in patients with a personal history of prostate cancer with intermediate-risk and intraductal/cribriform histology ( 22 ). Despite all these recommendations, herein, using real-world data and our expertise in genetic testing, we pinpoint this issue for the first time in Lebanon. Moreover, our data revealed that physicians were more likely to refer metastatic patients for genetic testing compared to those with high-risk localized or non-metastatic cases. This is consistent with the literature, as we observe similar trends in a survey from germline genetics working group of prostate clinical trials conducted by Paller CJ et al . where referrals in metastatic patients were observed in 62% vs 12% only in localized disease ( 23 ). From our perspective, several factors could explain the above deficiency in referral for genetic testing. The discrepancy between guideline criteria and their complexity may hinder the implementation of genetic testing. Additionally, the inclusion of family history and histopathologic characteristics—both inherently subjective—can further complicate interpretation. It is important to acknowledge the small sample size of our study, which can be attributed to two key factors: first, the relatively small population of our country, and second, the limited awareness surrounding referrals. Moreover, the lack of genetic counselors in Lebanon places a considerable burden on physician, requiring them to be well-versed in these guidelines to ensure accurate patient selection and effective communication. Despite these limitations, this study is a pioneering effort in highlighting the lack of genetic testing among prostate cancer patients in Lebanon. It serves as a crucial steppingstone for future research and the more rigorous implementation of international guidelines. Moreover, the lack of awareness about testing in Lebanon, classified as a developing country, is a significant concern. Disparities in germline testing rates among racial/ethnic minorities in the United States is highlighted in a study by Weise N et al ( 24 ). Indeed, low referral rates may be attributed to inadequate educational materials ( 21 ). This highlights an opportunity for enhancing education and awareness about germline testing as evidenced by a remarkable 118% increase in genetics referrals after educational sessions conducted for urologists, medical oncologists, and nurse navigators subjected in a recent study from the United States ( 25 ). Another approach to overcome barriers to genetic cancer risk assessment (GCRA) would be developing research protocols to gather data on genetic risk factors in local populations. Additionally, implementing telemedicine initiatives can increase access to genetic counseling and testing, particularly in underserved areas, while reducing logistical barriers. These efforts, among others, can help integrate genetic risk assessment into routine care, particularly in underdeveloped countries such as Lebanon. Another contributing factor to low referral rates is the significant cost associated with genetic testing, which is particularly pertinent in our country with known limited resources, and continuous economic crises. It has been reported that improving education and awareness about genetic testing, emphasizing its cost-effectiveness and dispelling the misconceptions can contribute to higher testing rates. This fact was supported by a study conducted in the US, highlighting that determining BRCA status for all low risk localized prostate cancer patients offers both short-term and long-term economic benefits ( 26 ). The low genetic testing rate in Lebanon underscores the urgent need for national strategies and targeted awareness campaigns. Our analyses showed that germline testing was requested more frequently by oncologists than urologists with a ratio of 4:1 in favor of oncologists. The reasons behind the low referrals among urologists have been previously analyzed in some studies, showing a significant gap in the knowledge of guidelines and appropriate referral timing ( 17 ), with only 4% of clinicians reporting formal education in genetics. One of the primary concerns was the complexity, time, and difficulty involved in constructing a family history pedigree ( 18 ). From their side, oncologists were more incorporated in this testing compared to urologists due to their higher capability in convincing their patients. Also, in a study conducted by Scheinberg et al , 95% of the patients reportedly accepted germline testing when offered by their medical oncologist ( 27 ). While looking at the results of our study, pathogenic variants carriers, and extrapolating to individuals diagnosed with prostate cancer in Lebanon, were treated with protocols designed for noncarriers, highlighting potential inadequacies in the current therapeutic approach. Castro et al. conducted a study in 2015 examining the impact of germline pathogenic variants in BRCA on treatment outcomes in prostate cancer within a cohort of 1302 patients. Their findings revealed that carriers who were treated with conventional modalities exhibited earlier metastasis and shorter survival compared to noncarriers ( 28 ). Indeed, the efficacy of PARP inhibitors in patients with metastatic prostate cancer who presented pathogenic variants in DNA repair genes have been demonstrated in the TOPARP-A trial ( 12 ). This study granted the FDA approval of two PARP inhibitors for use: Rucaparib studied first in a phase II study TRITON and Olaparib in a phase III, Profound study, that demonstrated improvement in progression free survival ( 29 , 30 , 31 , 32 ). In our study none of the four positive patients were treated with PARP inhibitors, thus not abiding to the international recommendations. Due to the current work, we believe that gaps in the Lebanese healthcare system, coupled with the absence of reimbursement, hinder adequate treatment for Lebanese prostate cancer patients harboring a pathogenic variant in an HRD gene and eligible for PARP inhibitors. This lack of access may negatively impact their outcomes and survival. Patient #16 for example, who was diagnosed with metastatic castration-resistant prostate cancer and carried a germline pathogenic variant could have benefited from specific therapy but have since deceased suggesting that the test timing was harmfully delayed. Finally, to note, robust evidence supporting the use of PARP inhibitors in mCRPC comes from patient selection based on the identification of somatic pathogenic variants in tumor tissue or liquid biopsy, which were not tested in our study ( 33 ). This underscores the importance of incorporating both genetic and somatic alterations in future studies to better inform treatment strategies. In our study, three of the individuals who tested positive did not suffer from prostate cancer but were referred for further evaluation based on family history and genetic studies. This underscores the importance of communicating risks not only to patients but also to their family members. Genetic counseling will address the implications of test results for family members, helping them understand their own risks and options for testing. Overall, this process is essential for proactive management, early detection, and tailored treatment plans of prostate cancer. For this reason, it is crucial to emphasize that low genetic testing rates can delay proper genetic counseling, screening, and ultimately, early disease detection. Conclusion Despite advancements in treatment modalities, along with the promising role of genetic testing for HRD pathogenic variants, the prognosis for metastatic prostate cancer remains relatively poor. The detection of gene alterations, notably germline pathogenic variants in BRCA2 , have been reported to impact treatment outcomes, highlighting the critical role of integrating genetic testing in personalized treatment strategies as supported by numerous clinical guidelines. However, genetic testing for prostate cancer remains scarce in clinical practice, especially for patients with localized disease, due to ambiguous guidelines and inconsistent practices. Our study sheds light on the low frequency of genetic testing for prostate cancer among oncologists and urologists in Lebanon, highlighting that current testing practices have had limited impact on treatment strategies. This underscores the need to raise more awareness to enhance genetic testing and integrate it into personalized medicine to improve patient outcomes. To address these challenges, it is crucial to develop clear national guidelines and promote greater awareness and education among healthcare professionals about the benefits of genetic testing. Also, it is important to enhance research protocols and implement telemedicine initiatives especially in developing countries, such as Lebanon. By bridging these gaps, we aim to elevate the standard of care for prostate cancer, ultimately improving survival rates for patients in developing countries with limited healthcare resources. Abbreviations PSA: prostate-specific antigen; NCCN :National Comprehensive Cancer Network HRD: homologous recombination deficiency; HRR:homologous recombination repair; PARP: poly (ADP-ribose) polymerase; CGGM: Center Jacques Loiselet for medical genetics and genomics; NGS: Next Generation sequencing; USJ: Saint Joseph University of Beirut; LHRH:luteinizing hormone-releasing hormone; ARB: Androgen receptor blocker; BRCA: BReast CAncer gene; CSPC: castration-sensitive prostate cancer; CRPC: castration-resistant prostate cancer; Declarations ● Ethics approval and consent to participate This document confirms the ethics approval and patient consent for participation in the study titled “Assessing Germline Genetic Testing Patterns, Awareness, and Adherence to Guidelines Among Lebanese Prostate Cancer Patients.” Informed oral consent was obtained from all participants, in accordance with the consent form provided in the supplementary material. The study was reviewed and approved by the Research Ethics Committee of Hôtel-Dieu de France and adheres to the principles outlined in the Declaration of Helsinki. Ethics Committee reference number: not applicable. Clinical trial number:not applicable ● Consent for publication The data presented was obtained following participants' informed oral consent, with the oral consent form provided in the supplementary material. ● Availability of data and materials The data in this study has not been deposited into a public database. All data presented in the manuscript is available and can be accessed upon request by contacting the corresponding author. ● Competing Interests The authors of this study declare that there are no competing interests associated with the research, writing, or publication of this article. ● Funding The authors of this study declare that there was no external funding or financial support received for the research, development, or publication of this article. ● Authors' contributions The primary authors of the work are Dr Samah Seif and Dr Tala Najdi Conception and design: S Seif, T Najdi; Administrative support: J Kattan; Provision of study materials or patients: S Seif, T Najdi, A Chebly; Collection and assembly of data: M Bassil, N Bou Atme, R Khnaisser; Data analysis and interpretation: S Seif, T Najdi, A Chebly; Manuscript writing: All authors; Final approval of manuscript: All authors. * SS and TN contributed equally. ● Acknowledgements We would like to express our sincere gratitude to the Center Jacques Loiselet for Medical Genetics and Genomics at the Faculty of Medicine at Saint Joseph University of Beirut, for providing necessary data and resources for this study. 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Germline Genetic Testing in Advanced Prostate Cancer; Practices and Barriers: Survey Results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium. Clin Genitourin Cancer. 2019;17(4):275–e2821. Weise N, Shaya J, Javier-Desloges J, Cheng HH, Madlensky L, McKay RR. Disparities in germline testing among racial minorities with prostate cancer. Prostate Cancer Prostatic Dis. 2022;25(3):403–10. Moody E, Larson M, Greenberg S, Jump T, Bell M, Gygi J, et al. Impact of provider education on prostate cancer genetic counseling referrals. JCO. 2022;40(6suppl):59–59. Oh M, McBride A, Bhattacharjee S, Slack M, Jeter J, Abraham I. Economic value of knowing BRCA status: BRCA testing for prostate cancer prevention and optimal treatment. Expert Rev Pharmacoecon Outcomes Res. 2023;23(3):297–307. Scheinberg T, Goodwin A, Ip E, Linton A, Mak B, Smith DP, et al. Evaluation of a Mainstream Model of Genetic Testing for Men With Prostate Cancer. JCO Oncol Pract. 2021;17(2):e204–16. Castro E, Jugurnauth-Little S, Karlsson Q, Al-Shahrour F, Piñeiro-Yañez E, Van de Poll F, et al. High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers. Ann Oncol. 2015 Nov;26(11):2293–300. Abida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, et al. Rucaparib in Men With Metastatic Castration- Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol. 2020;38(32):3763–72. de Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020;382(22):2091–102. Agarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul;22(10398):291–303. Chi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, et al. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023;41(18):3339–51. Markowski MC, Antonarakis ES. PARP inhibitors in prostate cancer: time to narrow patient selection? Expert Rev Anticancer Ther. 2020;20(7):523–6. 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-6337768","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":453759319,"identity":"71d6e39e-98b3-47d3-b723-babb84dca0f5","order_by":0,"name":"Samah Seif","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABEklEQVRIie3QMUvDQBTA8ScHz+VV15TT5itcKChiPkyydDLgJE4xIsRF6ZpByVcIBOr6QkbFueDSqZMBiyCFOnjFFqdLHQXvT8glw+94dwA22x9NLF8oal7965UA9tRGgoMAIPghtJEAnqgVgXbiXj+G76cQ93aQPiazOYT5JW9NmhTo0EDUU1TKDOo+YufBywIIC2bh3WtylBgIRIUk4DB1b0eSlgQYZUcTxYbBhk25IIgvUqSp/NQkT3h70UZgHOnNQQSIhFIfP0yYUbQRNW5Gx6RqL0U86N4MnH7B1VX37tkxnsUdRuULnceum4qpM/f9/Tyrq7fXM79nurH1Jaxz9FMl3x+/b9cwkM1ms/3bvgALxVME0MB5/wAAAABJRU5ErkJggg==","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":true,"prefix":"","firstName":"Samah","middleName":"","lastName":"Seif","suffix":""},{"id":453759320,"identity":"f40fa232-a275-440b-aeef-0c6b56e6024a","order_by":1,"name":"Tala Najdi","email":"","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Tala","middleName":"","lastName":"Najdi","suffix":""},{"id":453759321,"identity":"d1cc1c91-715b-432b-a82f-616aee4bf1ed","order_by":2,"name":"Alain Chebly","email":"","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Alain","middleName":"","lastName":"Chebly","suffix":""},{"id":453759322,"identity":"71721bb9-47bf-4817-a0d1-216a119f54b4","order_by":3,"name":"Marita Bassil","email":"","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Marita","middleName":"","lastName":"Bassil","suffix":""},{"id":453759323,"identity":"df0f12d3-1b6b-4b83-bcfb-08f46eeb1130","order_by":4,"name":"Nour Bou Atme","email":"","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Nour","middleName":"Bou","lastName":"Atme","suffix":""},{"id":453759325,"identity":"ac454235-340e-43b7-b824-a2348cb551bb","order_by":5,"name":"Rouba Khnaisser","email":"","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Rouba","middleName":"","lastName":"Khnaisser","suffix":""},{"id":453759327,"identity":"fc42d1ea-e94c-45e3-9787-dfb961e5d11c","order_by":6,"name":"Joseph Kattan","email":"","orcid":"","institution":"Saint Joseph University of Beirut","correspondingAuthor":false,"prefix":"","firstName":"Joseph","middleName":"","lastName":"Kattan","suffix":""}],"badges":[],"createdAt":"2025-03-30 09:38:11","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6337768/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6337768/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":82362346,"identity":"cce4da07-5887-471c-837f-3e97823ef91b","added_by":"auto","created_at":"2025-05-09 12:01:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":874476,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6337768/v1/f1d2c4a6-c5d7-42f6-8adc-10319ec93081.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Assessing Germline Genetic Testing Patterns, Awareness, and Adherence to Guidelines Among Lebanese Prostate Cancer Patients","fulltext":[{"header":"Introduction","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eProstate cancer stands as the most prevalent cancer among men globally and specifically in Lebanon. It is also known to be the second most deadly after lung cancer (\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e)(\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e). The age-standardized incidence rate of prostate cancer in Lebanon has exhibited a noteworthy increase from 29.1 per 100,000 in 2005 to 37.3 per 100,000 in 2016, surpassing the global average incidence rate in 2012. This incidence is highly dependent on screening practices involving prostate-specific antigen (PSA) and the number of PSA-driven biopsies (\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eThe median overall survival for metastatic prostate cancer has traditionally ranged from 18 to 36 months. However, recent clinical trials such as PEACE-1 and ARASENS have demonstrated that patients with advanced prostate cancer can achieve median survival rates exceeding 36 months, with some reaching over 5 years. This improvement is likely attributed to the combined benefits of new antiandrogens and subsequent treatments, including PARP inhibitors\u003c/p\u003e\u003cp\u003eThe median overall survival (OS) for metastatic prostate cancer has traditionnaly ranged from 18 to 36 months (\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e). However, recent clinical trials such as PEACE-1 and ARASENS have demonstrated that patients with advanced prostate cancer can achieve median survival rates exceeding 36 months, with some reaching over 5 years (\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e)(\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e). This improvement is likely attributed to the combined benefits of new antiandrogens and subsequents treatments. In the process of cancer progression, cancer cells are prone to defects in DNA repair and evolve to an aggressive phenotype (\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e). DNA damage response (DDR) pathway is implicated in maintaining genomic stability. Any defect or pathogenic variant in a gene implicated in this pathway can lead to prostate cancer (\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eDDR germline or somatic alterations are found in 23% of metastatic prostate cancer according to the International Stand Up to Cancer/Prostate Cancer Foundation/American Association for Cancer Research Prostate Cancer Team (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e). The BReast CAncer gene 2 (\u003cem\u003eBRCA2)\u003c/em\u003e, which is the most mutated gene in prostate cancer, functions as a tumor suppressor gene, playing a pivotal role in the DNA repair mechanism by regulating homologous recombination (HR). Moreover, it has been demonstrated that these pathogenic variants increase the risk of prostate cancer with an estimation of 15% by the age of 65 (\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e). Later, other studies demonstrated that mutated \u003cem\u003eBRCA2\u003c/em\u003e was correlated with more advanced stage, high grade and poorer survival (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e). There is also evidence of multiple other mutated genes, such as \u003cem\u003eATM\u003c/em\u003e 1.6%, \u003cem\u003eCHEK2\u003c/em\u003e 1.9%, \u003cem\u003eBRCA1\u003c/em\u003e 0.9%, \u003cem\u003eRAD51D\u003c/em\u003e 0.4%, and \u003cem\u003ePALB2\u003c/em\u003e 0.4% (\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e, \u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eNowadays, \u003cem\u003eBRCA\u003c/em\u003e testing is usually done in breast, ovarian and other hereditary cancers, but there is less consensus regarding testing in prostate cancer. According to a recent review guidelines and consensus, genetic testing is offered in men with metastatic disease, but less clear consensus was found in men with localized disease due to its higher incidence in patients with metastases (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eMetastatic prostate or recurrent prostate cancer progresses through various stages, initially starting as castration-sensitive (mCSPC), where androgen deprivation therapy proves highly effective. However, as the disease advances, it transitions to a castration-resistant stage (mCRPC). Despite the continued use of androgen deprivation therapy, new generation anti-androgen therapy and Taxane chemotherapy, the efficacy diminishes, leading to a limited range of treatment options. Indeed, castration-resistant stage poses significant challenges (\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e). Many studies have been conducted on the use of genetic testing to guide treatment options for metastatic patients, yielding promising results, particularly through the inhibition of poly (ADP-ribose) polymerase (PARP) enzymes in patients with a pathogenic variant in \u003cem\u003eBRCA\u003c/em\u003e or other homologous recombination deficiency (HRD) genes.\u003c/p\u003e\u003cp\u003eConsidering these advancements, genetic testing, mainly by NGS panels, has become essential, not only for assessing hereditary transmission but also as a valuable tool in therapeutic decision-making. However, various factors may influence the frequency of requested molecular tests, particularly in countries with less stringent regulations and continuous economic crisis, such as Lebanon. In Lebanon, genetic cancer risk assessment is mainly managed by the treating physician, to identify eligible patients and provide necessary information before referring them for genetic testing. In the current study, we investigate the adherence to genetic testing recommendations in Lebanese patients with prostate cancer and assess its impact on guiding treatment decisions in clinical practice.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Materials and methods","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eData from prostate cancer patients referred for genetic testing between 2013 and January 2025 was collected from the Center Jacques Loiselet for medical genetics and genomics (CGGM), at the faculty of medicine, Saint Joseph University of Beirut (USJ), Lebanon. This retrospective study was approved by the ethical committee at Saint Joseph University of Beirut and Hotel Dieu de France, Lebanon.\u003c/p\u003e\u003cp\u003eGenetic testing was performed on peripheral blood samples from the patients to screen for germline variants in a panel of genes by Next Generation Sequencing (NGS). After preparation, the final indexed libraries were sequenced on an Illumina platform. In this analysis, the following regions were targeted: coding regions of the panel genes, 10 bp of flanking intronic sequences, and known pathogenic/likely pathogenic variants within these genes included in the enrichment design. The analyzed genes are the following: \u003cem\u003eAPC, ATM, AXIN2, BAP1, BARD1, BLM, BMPR1A, BRCA1, BRCA2, BRIP1, CDH1, CDK4, CDKN2A, CHEK2, DICER1, DIS3L2, EPCAM, FANCC, FH, FLCN, GALNT12, HOXB13, KIT, MC1R,MEN1, MET, MITF, MLH1, MLH3, MRE11, MSH2, MSH3, MSH6, MUTYH, NBN, NF1, NTHL1, PALB2, PMS2, POLD1, POLE, POT1, PRSS1, PTCH1, PTEN, RAD50, RAD51C, RAD51D,RECQL, RET, RNF43, RPS20, SDHA, SDHAF2, SDHB, SDHC, SDHD, SMAD4, SMARCA4, STK11, TP53, TSC1, TSC2, VHL, WT1, XRCC2 and XRCC3.\u003c/em\u003e\u003c/p\u003e\u003cp\u003eAdditionally, patients\u0026rsquo; data were collected from the laboratory and physician\u0026rsquo;s clinic, including demographics data, the year of diagnosis, metastatic stage, molecular testing date, and molecular results. Also, the specialty of the referring physician was recorded distinguishing between oncologists and urologists.\u003c/p\u003e\u003cp\u003ePatients were subsequently classified as either \u0026ldquo;positive\u0026rdquo; or \u0026ldquo;negative\u0026rdquo;. For those identified as positive, we contacted their physicians to determine whether PARP inhibitor therapy had been prescribed. This analysis aimed to evaluate the impact of genetic status on treatment decisions. Ultimately, the aim was to provide insights into the clinical utility of genetic testing in managing prostate cancer, particularly in a developing country like Lebanon, where medical and financial resources are limited.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003c/p\u003e\n\u003cp\u003eIn our study, only twenty prostate cancer patients were referred to our center (CGGM) for genetic testing by NGS, over a period of 12 years. Our center is a leading tertiary reference center in Lebanon and one of the largest and most reputable in the country. Data of these 20 patients were collected. The patient cohort exhibited diverse characteristics, which are summarized in Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e. The median age was 66 years, ranging between 47 and 77 years. The median age at diagnosis was sixty. In two of our patients (#13 and #14), a diagnosis of prostate cancer was made but no data was available regarding the time and age at diagnosis and their gleason score. Among the referrals, 15% were made by urologists, while the majority (85%) was referred by the oncologists \u003cstrong\u003e(\u003c/strong\u003eTable \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e\u003cstrong\u003e).\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eInterestingly, none of the patients were referred at the time of diagnosis. Instead, patients experienced an average delay of at least 3 years before being referred for genetic testing. Referrals primarily occurred due to disease progression, including metastasis or the development of CRPC. Only four patients were considered metastatic castration sensitive.\u003c/p\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u0026nbsp;\u003c/p\u003e\n\u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eCohort characteristics and results\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDiagnosis year\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAge at\u003c/p\u003e\n \u003cp\u003ediagnosis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGleason Score\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMetastasis Date of diagnosis\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreatment of HSPC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDate of castration resistan ce\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eTreatment of CRPC\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eYear of genetic testing\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eReferring physician\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eReason for referral\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGenetic Test result\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eUse of PARP\u003c/p\u003e\n \u003cp\u003einhibit ors\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e1\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e67\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016 -\u003c/p\u003e\n \u003cp\u003epelvic nodes and bones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLHRH agonist (Leuprolide)\u0026thinsp;+\u0026thinsp;Chemotherapy (Docetaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019: ARB\u003c/p\u003e\n \u003cp\u003e(Enzalutamide)\u003c/p\u003e\n \u003cp\u003e2021:\u003c/p\u003e\n \u003cp\u003eChemotherapy\u003c/p\u003e\n \u003cp\u003e(Cabazitaxel) +\u003c/p\u003e\n \u003cp\u003eLHRH Agonist (Gosereline)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e75\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003cp\u003epulmonary and bones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u003c/p\u003e\n \u003cp\u003e+ ARB (Bicalutamide)\u003c/p\u003e\n \u003cp\u003e\u0026rarr; Chemotherapy (Docetaxel)\u0026thinsp;+\u0026thinsp;Abiraterone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enon CRPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e3\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e52\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003cp\u003ebones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;ARB (Bicalutamide)\u0026thinsp;+\u0026thinsp;Chemotherapy (Docetaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003enon CRPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRegular testing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e4\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2018 -\u003c/p\u003e\n \u003cp\u003epelvic lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical 2009\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2014\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2014:\u003c/p\u003e\n \u003cp\u003eLHRH\u003c/p\u003e\n \u003cp\u003eantagonist\u0026thinsp;+\u0026thinsp;ARB\u003c/p\u003e\n \u003cp\u003e(Enzalutamide)\u003c/p\u003e\n \u003cp\u003e2022: Chemotherapy (Cabazitaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e5\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020 -\u003c/p\u003e\n \u003cp\u003ebones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical\u0026thinsp;+\u0026thinsp;radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChemotherapy (Docetaxel\u0026loz; Cabazitaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e68\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHormonotherapy\u003c/p\u003e\n \u003cp\u003e+ Radiotherapy 2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAbiraterone\u0026thinsp;+\u0026thinsp;Chemotherapy (Docetaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2012\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eX\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e85\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot determ ined on biopsy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019 -\u003c/p\u003e\n \u003cp\u003enodes and bones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical\u0026thinsp;+\u0026thinsp;Abiraterone\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChemotherapy (Docetaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot diagnosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eBRCA2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e43\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot metastatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHormonotherapy\u003c/p\u003e\n \u003cp\u003e+ radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon CRPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily history\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eBRCA2\u003c/em\u003e\u003c/p\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e11\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003cp\u003ebones \u0026minus;\u0026thinsp;2021\u003c/p\u003e\n \u003cp\u003ehepatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical \u0026rarr; LHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;ARB (Bicalutamide)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017: LHRH agonist (Gosereline)+ ARB (Enzalu amide)\u003c/p\u003e\n \u003cp\u003e2019:\u003c/p\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;Chemotherapy (Cabazitaxel)\u0026thinsp;+\u0026thinsp;Abiraterone\u003c/p\u003e\n \u003cp\u003e2021:\u003c/p\u003e\n \u003cp\u003eChemotherapy (Docetaxel\u0026thinsp;+\u0026thinsp;Carboplatine)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCRPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e12\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e53\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2010-\u003c/p\u003e\n \u003cp\u003ePelvic lymph nodes\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSurgical\u0026thinsp;+\u0026thinsp;LHRH antagonist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017:\u003c/p\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u003c/p\u003e\n \u003cp\u003e+\u003c/p\u003e\n \u003cp\u003eChemotherapy (Docetaxel) 2018:\u003c/p\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;chemotherapy (Cabazitaxel)\u003c/p\u003e\n \u003cp\u003e2020:\u003c/p\u003e\n \u003cp\u003eAbiraterone\u0026thinsp;+\u0026thinsp;ARB (Enzalutamide)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e13\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot Diagnosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily History\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e14\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNot diagnosed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFamily History\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e58\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG8\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOrchidectomy\u0026thinsp;+\u0026thinsp;Chemotherapy (Taxotere)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2017\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChemotherapy (Cabazitaxel)\u0026thinsp;+\u0026thinsp;Bone radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2018\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eMSH2\u003c/em\u003e +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e61\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLHRHagonist (Gosereline)\u0026thinsp;+\u0026thinsp;Pelvic irradiation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2019: LHRH agonist\u003c/p\u003e\n \u003cp\u003e(Gosereline)\u0026thinsp;+\u0026thinsp;ARB (Enzalutamide)\u003c/p\u003e\n \u003cp\u003e2020: Chemotherapy (Cabazitaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2021\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eMSH2\u003c/em\u003e +\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e17\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e69\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHepatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;Chemotherapy (Docetaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2016:\u003c/p\u003e\n \u003cp\u003eARB (Enzalutamide)\u003c/p\u003e\n \u003cp\u003e2019: Chemotherapy (Cabazitaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e18\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2010\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e62\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG7\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022 -\u003c/p\u003e\n \u003cp\u003epulmonary and bones\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2011: Radiotherapy\u0026thinsp;+\u0026thinsp;LHRH agonist (Gosereline)\u003c/p\u003e\n \u003cp\u003e2022:\u003c/p\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;Bicalutamide\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2022: LHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;ARB (Apalutamide)\u003c/p\u003e\n \u003cp\u003e2024: Chemotherapy (Docetaxel\u0026loz; Cabazitaxel)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2023\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e19\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e50\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG6\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon metastatic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTreatment not started yet\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAt diagnosis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e20\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2020\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e49\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eG9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBone metastases\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLHRH agonist (Gosereline)\u0026thinsp;+\u0026thinsp;Abiraterone +\u003c/p\u003e\n \u003cp\u003eChemotherapy (Docetaxel) Radiotherapy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNon CRPC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e2024\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOncologist\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDisease progression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e-\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eLHRH:luteinizing hormone-releasing hormone; ARB: Androgen receptor blocker; BRCA: BReast CAncer gene; G:Grade; CRPC: castration-resistant prostate cancer; NA: Not Available; +: Positive ; -: Negative; \u0026agrave;: Then\u003c/em\u003e\u003c/p\u003e\n\u003cdiv class=\"BlockQuote\"\u003e\n \u003cp\u003eOut of the twenty patients tested, only four (20%) tested positive. Among these four cases, two unrelated patients showed the same pathogenic variant in the \u003cem\u003eBRCA2\u003c/em\u003e gene, and the other two patients showed two different variants in \u003cem\u003eMSH2\u003c/em\u003e. The list of these variants and their classification are represented in Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e. Interestingly, four of our patients who tested positive were referred initially for genetic counseling regarding a family history of prostate cancer, one had a localized disease, and the three others didn\u0026rsquo;t develop prostate cancer. Three patients presented confirmed pathogenic germline variants, while only one \u003cem\u003eMSH2\u003c/em\u003e variant was classified as Variant of Uncertain Significance (VUS). Intriguingly, none of the four patients with positive germline findings, initiated treatment with PARP inhibitors.\u0026nbsp;\u003c/p\u003e\n\u003c/div\u003e\n\u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eThe identified variants in 4 Lebanese prostate cancer patients\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePatient\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eGene\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eVariant\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eClassification (according to ClinVar)\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e9\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eBRCA2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec.6308C\u0026thinsp;\u0026gt;\u0026thinsp;A, p.(Ser2103 *)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePathogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e10\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eBRCA2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec.6308C\u0026thinsp;\u0026gt;\u0026thinsp;A, p.(Ser2103 *)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePathogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e15\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eMSH2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec.1331G\u0026thinsp;\u0026gt;\u0026thinsp;T, p.(Arg444Leu)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConflicting interpretations of pathogenicity, VUS\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e16\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u003cem\u003eMSH2\u003c/em\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ec.1552_1553del, p.(Gln518Valfs*10)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePathogenic\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n\u003c/table\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eIn this study, we report for the first on the molecular spectrum of prostate cancer patients in Lebanon. Such data are scarce and not available in the medical literature. Our study found pathogenic variants in the HRD gene among the four positive cases (20%). We found 10% \u003cem\u003eBRCA2\u003c/em\u003e-positive and 10% \u003cem\u003eMSH2\u003c/em\u003e-positive cases, aligning with worldwide data indicating that HRD alterations are the most prevalent in prostate cancer patients (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). Pritchard \u003cem\u003eet al.\u003c/em\u003e reported a substantial incidence of germline pathogenic variants in \u003cem\u003eBRCA2\u003c/em\u003e in advanced prostate cancer cases, which was corroborated by Robinson \u003cem\u003eet al.\u003c/em\u003e's findings of both somatic and germline \u003cem\u003eBRCA2\u003c/em\u003e alterations in metastatic prostate cancer (\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e). Furthermore, a broader study in men with early and advanced prostate cancer reaffirmed the frequency of pathogenic variants in the DNA repair genes. The most common mutated genes were \u003cem\u003eBRCA2\u003c/em\u003e and \u003cem\u003eATM\u003c/em\u003e, followed by \u003cem\u003eMSH6\u003c/em\u003e and \u003cem\u003eMSH2\u003c/em\u003e(\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e). These collective findings, and our study, underscore germline pathogenic variants in \u003cem\u003eBRCA2\u003c/em\u003e as the most prevalent and clinically significant in prostate cancer.\u003c/p\u003e\u003cp\u003eOur study clearly demonstrates that genetic testing referrals for prostate cancer cases are low, as we have identified only 20 referrals out of all the prostate cancer cases from 2013 till 2025. This aligns with international reports showing that genetic testing for prostate cancer is still low. Following the 2017 National Comprehensive Cancer Network\u0026reg; (NCCN\u0026reg;) guidelines, which advocate for germline testing of DNA repair genes in all men with high- or very-high-risk clinically localized prostate cancer and metastatic prostate cancer (NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines\u0026reg;) for Prostate Cancer V.2.2017), there has been a noted increase in homologous recombination repair (HRR) gene testing. Despite this uptick, the overall testing rates have remained low at around 13% (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). Nowadays, following the 2024 version of NCCN guidelines, it is recommended to perform germline genetic testing for patients with prostate cancer and a suggestive family history or high-risk, very-high-risk, regional, or metastatic prostate cancer regardless of family history, Ashkenazi Jewish ancestry or a personal history of breast cancer. In addition, germline genetic testing should be considered in patients with a personal history of prostate cancer with intermediate-risk and intraductal/cribriform histology (\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e). Despite all these recommendations, herein, using real-world data and our expertise in genetic testing, we pinpoint this issue for the first time in Lebanon.\u003c/p\u003e\u003cp\u003eMoreover, our data revealed that physicians were more likely to refer metastatic patients for genetic testing compared to those with high-risk localized or non-metastatic cases. This is consistent with the literature, as we observe similar trends in a survey from germline genetics working group of prostate clinical trials conducted by Paller CJ et \u003cem\u003eal\u003c/em\u003e. where referrals in metastatic patients were observed in 62% vs 12% only in localized disease (\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eFrom our perspective, several factors could explain the above deficiency in referral for genetic testing. The discrepancy between guideline criteria and their complexity may hinder the implementation of genetic testing. Additionally, the inclusion of family history and histopathologic characteristics\u0026mdash;both inherently subjective\u0026mdash;can further complicate interpretation. It is important to acknowledge the small sample size of our study, which can be attributed to two key factors: first, the relatively small population of our country, and second, the limited awareness surrounding referrals. Moreover, the lack of genetic counselors in Lebanon places a considerable burden on physician, requiring them to be well-versed in these guidelines to ensure accurate patient selection and effective communication. Despite these limitations, this study is a pioneering effort in highlighting the lack of genetic testing among prostate cancer patients in Lebanon. It serves as a crucial steppingstone for future research and the more rigorous implementation of international guidelines.\u003c/p\u003e\u003cp\u003eMoreover, the lack of awareness about testing in Lebanon, classified as a developing country, is a significant concern. Disparities in germline testing rates among racial/ethnic minorities in the United States is highlighted in a study by Weise N et \u003cem\u003eal\u003c/em\u003e (\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e). Indeed, low referral rates may be attributed to inadequate educational materials (\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e). This highlights an opportunity for enhancing education and awareness about germline testing as evidenced by a remarkable 118% increase in genetics referrals after educational sessions conducted for urologists, medical oncologists, and nurse navigators subjected in a recent study from the United States (\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e). Another approach to overcome barriers to genetic cancer risk assessment (GCRA) would be developing research protocols to gather data on genetic risk factors in local populations. Additionally, implementing telemedicine initiatives can increase access to genetic counseling and testing, particularly in underserved areas, while reducing logistical barriers. These efforts, among others, can help integrate genetic risk assessment into routine care, particularly in underdeveloped countries such as Lebanon.\u003c/p\u003e\u003cp\u003eAnother contributing factor to low referral rates is the significant cost associated with genetic testing, which is particularly pertinent in our country with known limited resources, and continuous economic crises. It has been reported that improving education and awareness about genetic testing, emphasizing its cost-effectiveness and dispelling the misconceptions can contribute to higher testing rates. This fact was supported by a study conducted in the US, highlighting that determining \u003cem\u003eBRCA\u003c/em\u003e status for all low risk localized prostate cancer patients offers both short-term and long-term economic benefits (\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e). The low genetic testing rate in Lebanon underscores the urgent need for national strategies and targeted awareness campaigns.\u003c/p\u003e\u003cp\u003eOur analyses showed that germline testing was requested more frequently by oncologists than urologists with a ratio of 4:1 in favor of oncologists. The reasons behind the low referrals among urologists have been previously analyzed in some studies, showing a significant gap in the knowledge of guidelines and appropriate referral timing (\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e), with only 4% of clinicians reporting formal education in genetics. One of the primary concerns was the complexity, time, and difficulty involved in constructing a family history pedigree (\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e). From their side, oncologists were more incorporated in this testing compared to urologists due to their higher capability in convincing their patients. Also, in a study conducted by Scheinberg et \u003cem\u003eal\u003c/em\u003e, 95% of the patients reportedly accepted germline testing when offered by their medical oncologist (\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eWhile looking at the results of our study, pathogenic variants carriers, and extrapolating to individuals diagnosed with prostate cancer in Lebanon, were treated with protocols designed for noncarriers, highlighting potential inadequacies in the current therapeutic approach. Castro et \u003cem\u003eal.\u003c/em\u003e conducted a study in 2015 examining the impact of germline pathogenic variants in \u003cem\u003eBRCA\u003c/em\u003e on treatment outcomes in prostate cancer within a cohort of 1302 patients. Their findings revealed that carriers who were treated with conventional modalities exhibited earlier metastasis and shorter survival compared to noncarriers (\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e). Indeed, the efficacy of PARP inhibitors in patients with metastatic prostate cancer who presented pathogenic variants in DNA repair genes have been demonstrated in the TOPARP-A trial (\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e). This study granted the FDA approval of two PARP inhibitors for use: Rucaparib studied first in a phase II study TRITON and Olaparib in a phase III, Profound study, that demonstrated improvement in progression free survival (\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e, \u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e, \u003cspan citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e). In our study none of the four positive patients were treated with PARP inhibitors, thus not abiding to the international recommendations.\u003c/p\u003e\u003cp\u003eDue to the current work, we believe that gaps in the Lebanese healthcare system, coupled with the absence of reimbursement, hinder adequate treatment for Lebanese prostate cancer patients harboring a pathogenic variant in an HRD gene and eligible for PARP inhibitors. This lack of access may negatively impact their outcomes and survival. Patient #16 for example, who was diagnosed with metastatic castration-resistant prostate cancer and carried a germline pathogenic variant could have benefited from specific therapy but have since deceased suggesting that the test timing was harmfully delayed. Finally, to note, robust evidence supporting the use of PARP inhibitors in mCRPC comes from patient selection based on the identification of somatic pathogenic variants in tumor tissue or liquid biopsy, which were not tested in our study (\u003cspan citationid=\"CR33\" class=\"CitationRef\"\u003e33\u003c/span\u003e). This underscores the importance of incorporating both genetic and somatic alterations in future studies to better inform treatment strategies.\u003c/p\u003e\u003cp\u003eIn our study, three of the individuals who tested positive did not suffer from prostate cancer but were referred for further evaluation based on family history and genetic studies. This underscores the importance of communicating risks not only to patients but also to their family members. Genetic counseling will address the implications of test results for family members, helping them understand their own risks and options for testing. Overall, this process is essential for proactive management, early detection, and tailored treatment plans of prostate cancer. For this reason, it is crucial to emphasize that low genetic testing rates can delay proper genetic counseling, screening, and ultimately, early disease detection.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003e\u003cdiv class=\"BlockQuote\"\u003e\u003cp\u003eDespite advancements in treatment modalities, along with the promising role of genetic testing for HRD pathogenic variants, the prognosis for metastatic prostate cancer remains relatively poor. The detection of gene alterations, notably germline pathogenic variants in \u003cem\u003eBRCA2\u003c/em\u003e, have been reported to impact treatment outcomes, highlighting the critical role of integrating genetic testing in personalized treatment strategies as supported by numerous clinical guidelines. However, genetic testing for prostate cancer remains scarce in clinical practice, especially for patients with localized disease, due to ambiguous guidelines and inconsistent practices.\u003c/p\u003e\u003cp\u003eOur study sheds light on the low frequency of genetic testing for prostate cancer among oncologists and urologists in Lebanon, highlighting that current testing practices have had limited impact on treatment strategies. This underscores the need to raise more awareness to enhance genetic testing and integrate it into personalized medicine to improve patient outcomes. To address these challenges, it is crucial to develop clear national guidelines and promote greater awareness and education among healthcare professionals about the benefits of genetic testing. Also, it is important to enhance research protocols and implement telemedicine initiatives especially in developing countries, such as Lebanon. By bridging these gaps, we aim to elevate the standard of care for prostate cancer, ultimately improving survival rates for patients in developing countries with limited healthcare resources.\u003c/p\u003e\u003c/div\u003e\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003e\u003cem\u003ePSA: prostate-specific antigen; NCCN :National Comprehensive Cancer Network HRD: homologous recombination deficiency; HRR:homologous recombination repair; PARP: poly (ADP-ribose) polymerase; CGGM: Center Jacques Loiselet for medical genetics and genomics; NGS: Next Generation sequencing; USJ: Saint Joseph University of Beirut; LHRH:luteinizing hormone-releasing hormone; ARB: Androgen receptor blocker; BRCA: BReast CAncer gene; CSPC: castration-sensitive prostate cancer; CRPC: castration-resistant prostate cancer;\u0026nbsp;\u003c/em\u003e\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e● Ethics approval and consent to participate\u003c/p\u003e\n\u003cp\u003eThis document confirms the ethics approval and patient consent for participation in the study titled “Assessing Germline Genetic Testing Patterns, Awareness, and Adherence to Guidelines Among Lebanese Prostate Cancer Patients.”\u0026nbsp;Informed oral consent was obtained from all participants, in accordance with the consent form provided in the supplementary material.\u003c/p\u003e\n\u003cp\u003eThe study was reviewed and approved by the Research Ethics Committee of Hôtel-Dieu de France and adheres to the principles outlined in the Declaration of Helsinki.\u003c/p\u003e\n\u003cp\u003eEthics Committee reference number: not applicable.\u003c/p\u003e\n\u003cp\u003eClinical trial number:not applicable\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u0026nbsp;● Consent for publication\u003c/p\u003e\n\u003cp\u003eThe data presented was obtained following participants' informed oral consent, with the oral consent form provided in the supplementary material.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u0026nbsp;● Availability of data and materials\u003c/p\u003e\n\u003cp\u003eThe data in this study has not been deposited into a public database. All data presented in the manuscript is available and can be accessed upon request by contacting the corresponding author.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u0026nbsp;● Competing Interests\u003c/p\u003e\n\u003cp\u003eThe authors of this study declare that there are no competing interests associated with the research, writing, or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u0026nbsp;● Funding\u003c/p\u003e\n\u003cp\u003eThe\u0026nbsp;authors\u0026nbsp;of\u0026nbsp;this\u0026nbsp;study\u0026nbsp;declare\u0026nbsp;that\u0026nbsp;there\u0026nbsp;was\u0026nbsp;no\u0026nbsp;external\u0026nbsp;funding\u0026nbsp;or\u0026nbsp;financial\u0026nbsp;support\u0026nbsp;received\u0026nbsp;for\u0026nbsp;the\u0026nbsp;research,\u0026nbsp;development,\u0026nbsp;or publication of this article.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u0026nbsp;● Authors' contributions\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eThe primary authors of the work are Dr Samah Seif and Dr Tala Najdi\u003c/strong\u003e\u003c/p\u003e\n\u003col\u003e\n \u003cli\u003eConception\u0026nbsp;and\u0026nbsp;design:\u0026nbsp;S Seif,\u0026nbsp;T\u0026nbsp;Najdi;\u003c/li\u003e\n \u003cli\u003eAdministrative\u0026nbsp;support: J Kattan;\u003c/li\u003e\n \u003cli\u003eProvision\u0026nbsp;of study\u0026nbsp;materials\u0026nbsp;or patients: S Seif,\u0026nbsp;T Najdi, A Chebly;\u003c/li\u003e\n \u003cli\u003eCollection\u0026nbsp;and\u0026nbsp;assembly\u0026nbsp;of\u0026nbsp;data:\u0026nbsp;M Bassil,\u0026nbsp;N\u0026nbsp;Bou\u0026nbsp;Atme,\u0026nbsp;R Khnaisser;\u003c/li\u003e\n \u003cli\u003eData\u0026nbsp;analysis\u0026nbsp;and interpretation:\u0026nbsp;S\u0026nbsp;Seif, T\u0026nbsp;Najdi,\u0026nbsp;A Chebly;\u003c/li\u003e\n \u003cli\u003eManuscript\u0026nbsp;writing:\u0026nbsp;All\u0026nbsp;authors;\u003c/li\u003e\n \u003cli\u003eFinal\u0026nbsp;approval\u0026nbsp;of manuscript:\u0026nbsp;All authors.\u003c/li\u003e\n\u003c/ol\u003e\n\u003cp\u003e*\u0026nbsp;SS\u0026nbsp;and\u0026nbsp;TN\u0026nbsp;contributed equally.\u003c/p\u003e\n\u003cp\u003e\u003cbr\u003e\u0026nbsp;● Acknowledgements\u003c/p\u003e\n\u003cp\u003eWe\u0026nbsp;would\u0026nbsp;like\u0026nbsp;to\u0026nbsp;express\u0026nbsp;our\u0026nbsp;sincere\u0026nbsp;gratitude\u0026nbsp;to\u0026nbsp;the\u0026nbsp;Center\u0026nbsp;Jacques\u0026nbsp;Loiselet\u0026nbsp;for\u0026nbsp;Medical\u0026nbsp;Genetics\u0026nbsp;and\u0026nbsp;Genomics\u0026nbsp;at\u0026nbsp;the\u0026nbsp;Faculty of Medicine at Saint Joseph University of Beirut, for providing necessary data and resources for this study.\u003c/p\u003e\n\u003cp\u003eWe appreciate the support and collaboration of the medical staff and researchers involved in genetic testing. Additionally, we acknowledge the contribution of our department of Hematology-Oncology at Hotel-Dieu de France University Hospital that facilitated this work. We extend our appreciation to colleagues who provided valuable discussions and insights during this research.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eCommon Cancer Types - NCI [Internet]. 2015 [cited 2024 Jan 25]. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.cancer.gov/types/common- cancers\u003c/span\u003e\u003cspan address=\"https://www.cancer.gov/types/common- cancers\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eLakkis NA, Osman MH. Prostate Cancer in Lebanon: Incidence, Temporal Trends, and Comparison to Countries From Different Regions in the World. 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N Engl J Med. 2016;375(5):443\u0026ndash;53.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMateo J, Carreira S, Sandhu S, Miranda S, Mossop H, Perez-Lopez R, et al. DNA-Repair Defects and Olaparib in Metastatic Prostate Cancer. N Engl J Med. 2015;373(18):1697\u0026ndash;708.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTuffaha H, Edmunds K, Fairbairn D, Roberts MJ, Chambers S, Smith DP et al. Guidelines for genetic testing in prostate cancer: a scoping review. Prostate Cancer Prostatic Dis. 2023;1\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMessina C, Cattrini C, Soldato D, Vallome G, Caffo O, Castro E, et al. BRCA Mutations in Prostate Cancer: Prognostic and Predictive Implications. J Oncol. 2020;2020:4986365.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWang BR, Chen YA, Kao WH, Lai CH, Lin H, Hsieh JT. Developing New Treatment Options for Castration-Resistant Prostate Cancer and Recurrent Disease. Biomedicines. 2022;10(8):1872.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eDall\u0026rsquo;Era MA, McPherson JD, Gao AC, DeVere White RW, Gregg JP, Lara PN. Germline and somatic DNA repair gene alterations in prostate cancer. Cancer. 2020;126(13):2980\u0026ndash;5.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShore N, Ionescu-Ittu R, Yang L, Lalibert\u0026eacute; F, Mahendran M, Lejeune D, et al. Real-world genetic testing patterns in metastatic castration-resistant prostate cancer. Future Oncol. 2021;17(22):2907\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNCCN [Internet]. [cited 2024 Aug 18]. Guidelines Detail. Clinical Practice Guidelines in Oncology: Prostate v. 2024. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.nccn.org/guidelines/guidelines-detail?category=1\u0026amp;id=1459\u003c/span\u003e\u003cspan address=\"https://www.nccn.org/guidelines/guidelines-detail?category=1\u0026amp;id=1459\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePaller CJ, Antonarakis ES, Beer TM, Borno HT, Carlo MI, George DJ, et al. Germline Genetic Testing in Advanced Prostate Cancer; Practices and Barriers: Survey Results from the Germline Genetics Working Group of the Prostate Cancer Clinical Trials Consortium. Clin Genitourin Cancer. 2019;17(4):275\u0026ndash;e2821.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eWeise N, Shaya J, Javier-Desloges J, Cheng HH, Madlensky L, McKay RR. Disparities in germline testing among racial minorities with prostate cancer. Prostate Cancer Prostatic Dis. 2022;25(3):403\u0026ndash;10.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMoody E, Larson M, Greenberg S, Jump T, Bell M, Gygi J, et al. Impact of provider education on prostate cancer genetic counseling referrals. JCO. 2022;40(6suppl):59\u0026ndash;59.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eOh M, McBride A, Bhattacharjee S, Slack M, Jeter J, Abraham I. Economic value of knowing BRCA status: BRCA testing for prostate cancer prevention and optimal treatment. Expert Rev Pharmacoecon Outcomes Res. 2023;23(3):297\u0026ndash;307.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eScheinberg T, Goodwin A, Ip E, Linton A, Mak B, Smith DP, et al. Evaluation of a Mainstream Model of Genetic Testing for Men With Prostate Cancer. JCO Oncol Pract. 2021;17(2):e204\u0026ndash;16.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCastro E, Jugurnauth-Little S, Karlsson Q, Al-Shahrour F, Pi\u0026ntilde;eiro-Ya\u0026ntilde;ez E, Van de Poll F, et al. High burden of copy number alterations and c-MYC amplification in prostate cancer from BRCA2 germline mutation carriers. Ann Oncol. 2015 Nov;26(11):2293\u0026ndash;300.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAbida W, Patnaik A, Campbell D, Shapiro J, Bryce AH, McDermott R, et al. Rucaparib in Men With Metastatic Castration- Resistant Prostate Cancer Harboring a BRCA1 or BRCA2 Gene Alteration. J Clin Oncol. 2020;38(32):3763\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Bono J, Mateo J, Fizazi K, Saad F, Shore N, Sandhu S, et al. Olaparib for Metastatic Castration-Resistant Prostate Cancer. N Engl J Med. 2020;382(22):2091\u0026ndash;102.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eAgarwal N, Azad AA, Carles J, Fay AP, Matsubara N, Heinrich D, et al. Talazoparib plus enzalutamide in men with first-line metastatic castration-resistant prostate cancer (TALAPRO-2): a randomised, placebo-controlled, phase 3 trial. Lancet. 2023 Jul;22(10398):291\u0026ndash;303.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eChi KN, Rathkopf D, Smith MR, Efstathiou E, Attard G, Olmos D, et al. Niraparib and Abiraterone Acetate for Metastatic Castration-Resistant Prostate Cancer. J Clin Oncol. 2023;41(18):3339\u0026ndash;51.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMarkowski MC, Antonarakis ES. PARP inhibitors in prostate cancer: time to narrow patient selection? Expert Rev Anticancer Ther. 2020;20(7):523\u0026ndash;6.\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":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Prostate cancer, genetic testing, HRD, germline variants, hereditary, personalized treatment, Lebanon","lastPublishedDoi":"10.21203/rs.3.rs-6337768/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6337768/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eProstate cancer is the most common cancer in men worldwide and the second most lethal after lung cancer. Despite poor prognosis for metastatic cases, treatment advances have extended survival. However, data on germline genetic testing in Lebanese prostate cancer patients is scarce. This study investigates the frequency and role of genetic testing in prostate cancer management in Lebanon, focusing on its impact on treatment decisions.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003ePathogenic variant status was assessed using an NGS panel. Data from the Saint Joseph University genetic lab (2013\u0026ndash;2022) was analyzed, including demographics, diagnosis year, testing dates, and treatment outcomes. Referral patterns between oncologists and urologists were compared, and the use of PARP inhibitors was discussed.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eOnly 20 patients were referred for genetic testing over 12 years. Our study's low referral rates reflect real-world data from a third-country setting. Among these, 15% were referred by urologists and 85% by oncologists. Of those tested, 20% were positive, two with BRCA2 mutations and two with MSH2 variants. Testing was mostly done after disease progression or metastasis, four were referred due to family history. None of the positive patients received PARP inhibitors.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003e The study revealed low genetic testing referral rates, consistent with global trends despite updated guidelines. Contributing factors include complex guidelines, limited provider awareness, and high testing costs. Interestingly, these factors are more pronounced in the context of our study. Improved education, clearer guidelines, and telemedicine access could boost genetic testing uptake, enhancing prostate cancer treatment standards and survival rates locally and globally, with a particular focus on developing countries including Lebanon.\u003c/p\u003e","manuscriptTitle":"Assessing Germline Genetic Testing Patterns, Awareness, and Adherence to Guidelines Among Lebanese Prostate Cancer Patients","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-05-09 11:37:17","doi":"10.21203/rs.3.rs-6337768/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"editorInvitedReview","content":"","date":"2026-05-10T14:17:50+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-30T11:40:13+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2026-04-27T14:33:12+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"219599305975599516054792222259384371406","date":"2026-04-25T12:40:39+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"66645824129860135995780209857618886191","date":"2026-04-24T11:18:58+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"8339613592462793233551664149591170467","date":"2026-04-23T10:29:27+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2025-05-28T00:33:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"283469738404544483155785115061670095244","date":"2025-05-15T04:42:42+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2025-05-06T10:07:58+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-04-29T18:16:52+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2025-04-10T03:23:41+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-04-09T14:58:09+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Urology","date":"2025-04-09T14:57:07+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-urology","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"buro","sideBox":"Learn more about [BMC Urology](http://bmcurol.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/buro/default.aspx","title":"BMC Urology","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"466b582f-c315-45c8-9c80-190ce5ab3d6a","owner":[],"postedDate":"May 9th, 2025","published":true,"recentEditorialEvents":[{"type":"editorInvitedReview","content":"","date":"2026-05-10T14:17:50+00:00","index":102,"fulltext":""}],"rejectedJournal":[],"revision":"","amendment":"","status":"under-review","subjectAreas":[],"tags":[],"updatedAt":"2025-05-09T11:37:17+00:00","versionOfRecord":[],"versionCreatedAt":"2025-05-09 11:37:17","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-6337768","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-6337768","identity":"rs-6337768","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}