{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:08:54Z","timestamp":1772168934472,"version":"3.50.1"},"update-to":[{"DOI":"10.12688\/f1000research.161612.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000}}],"reference-count":32,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T00:00:00Z","timestamp":1762732800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>Purpose The purpose of this systematic review is to investigate differences in pathological outcomes and safety between subcapsular orchiectomy and pharmacological androgen deprivation therapy (ADT) for prostate cancer management. Methods A systematic search was conducted on PubMed, Google Scholar, and ScienceDirect for original articles published until February 2024 that compared tumour characteristics, biochemical markers, and adverse effects associated with these treatments. The risk of bias from each study was assessed using the Newcastle Ottawa Scale and Risk of Bias-2 (ROB-2) tool. Results Eleven studies meeting the inclusion criteria were analysed. Both subcapsular orchiectomy and pharmacological ADT effectively reduced tumour size and prostate-specific antigen (PSA) levels. Subcapsular orchiectomy was linked to higher surgical complication rates. At the same time, due to its systemic pharmacological mechanisms, pharmacological ADT carries a greater risk of metabolic side effects, such as weight gain and insulin resistance. Conclusions Both subcapsular orchiectomy and pharmacological ADT are viable options for prostate cancer treatment. However, their differing safety and pharmacological profiles highlight the need for personalised treatment strategies based on individual patient factors and preferences. PROSPERO registration CRD42025634678 (17\/01\/2025).<\/ns3:p>","DOI":"10.12688\/f1000research.161612.2","type":"journal-article","created":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T04:45:08Z","timestamp":1762749908000},"page":"254","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Examining Differences in Pathological Outcomes and Safety for Prostate Cancer Patients Undergoing Either Subcapsular Orchiectomy or Medical Androgen Deprivation Therapy: A Systematic Review"],"prefix":"10.12688","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-7292-7693","authenticated-orcid":false,"given":"Erick","family":"Frapancah","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Indrawarman","family":"Soerohardjo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"2560","published-online":{"date-parts":[[2025,11,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"407-421","DOI":"10.1007\/s44197-023-00103-6","article-title":"Global Burden of Prostate Cancer and Association with Socioeconomic Status, 1990\u20132019: A Systematic Analysis from the Global Burden of Disease Study.","volume":"13","author":"W Zhang","year":"2023 May 6","journal-title":"J. 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Urol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"255-256","DOI":"10.1001\/jama.2011.2022","article-title":"Screening for osteoporosis in men receiving androgen deprivation therapy.","volume":"307","author":"S Alibhai","year":"2012","journal-title":"JAMA."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"187-192","DOI":"10.1038\/aja.2011.102","article-title":"Hematological changes during androgen deprivation therapy.","volume":"14","author":"M Grossmann","year":"2012","journal-title":"Asian J. Androl."},{"key":"ref8","doi-asserted-by":"publisher","first-page":"1-15","DOI":"10.1186\/s12935-020-01508-0","article-title":"Clinical implication of prognostic and predictive biomarkers for castration-resistant prostate cancer: a systematic review.","volume":"20","author":"S Tian","year":"2020","journal-title":"Cancer Cell Int."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The PRISMA 2020 statement: an updated guideline for reporting systematic reviews.","volume":"29","author":"M Page","year":"2021 Mar","journal-title":"BMJ."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1441-1447","DOI":"10.1016\/j.juro.2016.12.003","article-title":"Luteinizing Hormone-Releasing Hormone Agonists are Superior to Subcapsular Orchiectomy in Lowering Testosterone Levels of Men with Prostate Cancer: Results from a Randomized Clinical Trial.","volume":"197","author":"P \u00d8stergren","year":"2017 Jun","journal-title":"J. Urol."},{"key":"ref12","doi-asserted-by":"publisher","first-page":"82-89","DOI":"10.4103\/jwas.jwas_274_22","article-title":"Correlation Between Serum Prostate-Specific Antigen and Testosterone Following Bilateral Total Orchidectomy for Patients with Advanced Prostate Cancer in Jos, Nigeria.","volume":"13","author":"O Osunaiye","year":"2023","journal-title":"J. West Afr. Coll. Surg."},{"key":"ref13","doi-asserted-by":"publisher","first-page":"682.e1-682.e9","DOI":"10.1016\/j.urolonc.2020.05.005","article-title":"Comparative study of surgical orchidectomy and medical castration in treatment efficacy, adverse effects and cost based on a large prospective metastatic prostate cancer registry.","volume":"38","author":"Y Tan","year":"2020 Aug","journal-title":"Urol. Oncol. Semin. Orig. Investig."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e157-e166","DOI":"10.1016\/j.clgc.2019.09.020","article-title":"Utilisation and Outcomes of Surgical Castration in Comparison to Medical Castration in Metastatic Prostate Cancer.","volume":"18","author":"R Garje","year":"2020 Apr","journal-title":"Clin. Genitourin. Cancer."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"46-51","DOI":"10.1016\/0090-4295(91)80077-K","article-title":"Zoladex versus orchiectomy in treatment of advanced prostate cancer: a randomized trial. Zoladex Prostate Study Group.","volume":"37","author":"M Soloway","year":"1991 Jan","journal-title":"Urology."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"4313-4326","DOI":"10.1007\/s00520-019-05266-2","article-title":"Subcapsular orchiectomy versus total orchiectomy and LHRH analogue in the treatment of hormone-sensitive metastatic prostate cancer: a different perspective in evaluation of the psychosocial effects.","volume":"28","author":"I Selvi","year":"2020 Sep","journal-title":"Support Care Cancer."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"502-508","DOI":"10.1111\/j.1464-410X.1991.tb15195.x","article-title":"Comparison of LHRH Analogue (Zoladex) with Orchiectomy in Patients with Metastatic Prostatic Carcinoma.","volume":"67","author":"A Kaisary","year":"1991 May","journal-title":"Br. J. 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Metab."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-254\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-254\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-254\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,10]],"date-time":"2025-11-10T04:45:10Z","timestamp":1762749910000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-254\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":32,"URL":"https:\/\/doi.org\/10.12688\/f1000research.161612.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.161612.1","asserted-by":"subject"}],"has-review":[{"id-type":"doi","id":"10.5256\/f1000research.189352.r431087","asserted-by":"object"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-254\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.177664.r397793, Chaidir Arif Mochtar, Universitas Indonesia, Depok, West Java, 03 Sep 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-254\/v1#referee-response-397793","order":0,"name":"referee-response-397793","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Erick Frapancah<\/b>; \n<i>Posted: 05 Oct 2025<\/i>; Dear Reviewer, Thank you very much for your thoughtful and constructive comments on our manuscript. We highly appreciate your detailed review, which has helped us improve the clarity and quality of our work. Our responses to your points are as follows: \n<b>1.Comment 1:<\/b> \u201cIn the Methods section, the sentence \u2018The literature search started in [insert start date]\u2019 appears incomplete. I recommend that the authors clarify whether the initial year of the search is missing or if this is simply a typographical error.\u201d \n<b>Response: <\/b>We appreciate the reviewer\u2019s observation. This was indeed a typographical oversight that occurred during proofreading. The correct statement now reads: \u201cThe literature search was performed for evaluate and compare pathological outcomes, including disease progression, survival rates, and adverse effects, in prostate cancer patients undergoing either subcapsular orchiectomy or pharmacological ADT up to February 2024.\u201d We have revised the text accordingly in the Methods section.  \n<b>2.Comment 2:<\/b> \u201cWhile the inclusion criteria specify that eligible studies should compare surgical orchiectomy with ADT, two included studies (Arogundade et al. and Islam et al.) did not provide such a comparison but only reported outcomes of surgical orchiectomy. I suggest the authors address this inconsistency for greater clarity.\u201d \n<b>Response: <\/b>We thank the reviewer for highlighting this important point. Upon re-evaluation, we acknowledge that the studies by Arogundade et al. and Islam et al. did not meet our strict inclusion criteria, as they did not directly compare surgical orchiectomy with medical ADT. We have therefore excluded these two studies and categorized them as \u201cstudies not meeting the inclusion criteria\u201d in the updated PRISMA flowchart (Screening section). We also rechecked the data and confirmed that their exclusion did not affect the results or conclusions of our review.  \n<b>3.Comment 3:<\/b> \u201cIt should be noted that the studies included in this review were retrospective cohorts rather than prospective ones.\u201d \n<b>Response: <\/b>We thank the reviewer for this clarification. We have updated the manuscript and included 7 Randomized Controlled Trials, 3 Retrospective Cohort, and 1 Prospective cohort studies. This information is now clearly stated in the Results section.  \n<b>4. Comment 4:<\/b> \u201cThe statistical approach chosen by the authors is appropriate. Given the heterogeneity of the included studies, the decision not to perform a meta-analysis is justified and well explained. The narrative synthesis is clearly presented.\u201d \n<b>Response: <\/b>We sincerely appreciate the reviewer\u2019s positive feedback regarding our methodological approach and presentation.  \n<b>5. Additional Revisions:<\/b> \n<b>Response: <\/b>We have also corrected minor formatting inconsistencies, improved figure quality (including the PRISMA flowchart), and refined statistical terminology for clarity. All deleted text is shown with strikethrough and yellow highlight, while revisions and additions are highlighted in red. Reference numbering has been updated accordingly after the exclusion of the two studies. We hope these revisions address all comments satisfactorily and enhance the quality and clarity of our manuscript. Thank you again for your valuable time and insightful feedback.","URL":"https:\/\/f1000research.com\/articles\/14-254\/v2#referee-comment-14720","order":1,"name":"referee-comment-14720","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.177664.r412960, Syah Mirsya Warli, Universitas Sumatera Utara, Medan, 23 Sep 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-254\/v1#referee-response-412960","order":2,"name":"referee-response-412960","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Erick Frapancah<\/b>; \n<i>Posted: 05 Oct 2025<\/i>; Dear Reviewer, Thank you very much for your valuable and insightful comments on our manuscript. Your feedback has been instrumental in helping us improve the quality of our paper. We have addressed all the points raised as follows: \n<b>1. Study inclusion (Arogundade et al. and Islam et al.)<\/b> We acknowledge that the studies by Arogundade et al. and Islam et al. did not provide direct comparisons between surgical and medical ADT. We recognize that their inclusion was inconsistent with our strict inclusion criteria. Therefore, we have excluded these studies from our analysis and include them as \u201cstudies not meeting the inclusion criteria\u201d in the PRISMA flowchart (Screening section). After reanalysis, we confirmed that the exclusion of these studies did not affect the overall results or conclusions of our systematic review. \n<b>2. Literature search clarification<\/b> We also acknowledge the oversight in proofreading that resulted in the placeholder phrase \u201cThe literature search started in [insert start date]\u201d. This has been corrected, and we confirm that our literature search included all eligible studies published up to February 2024. \n<b>3. High Heterogeneity<\/b> We summarized the key findings from each included study in a structured manner, focusing on trends in oncologic outcomes, survival, and adverse effects between surgical orchiectomy and medical ADT. We qualitatively explored potential sources of heterogeneity, including differences in study design, treatment duration, and follow-up period, to better understand variations in results across studies. The methodological quality of each study was assessed using standardized criteria to support a more reliable interpretation of the evidence. Finally, we discussed both the consistency and discrepancies among the studies to highlight areas where findings converged or differed, thereby providing a comprehensive narrative synthesis of the current evidence. \n<b>4. Minor revisions and formatting improvements<\/b> We have addressed all minor issues, including inconsistencies in citation style and figure quality. The PRISMA flowchart has been updated with higher resolution, and statistical terminology has been refined for clarity. All deleted text is shown with a strikethrough and yellow highlight, while all revised or added text is highlighted in red. Following the exclusion of the two aforementioned studies, we also updated the reference numbering accordingly.  We sincerely hope that these revisions improve the quality of our manuscript and that it now meets the publication standards of F1000Research. Thank you once again for your constructive comments and valuable time.  Warm regards, Erick Frapancah (on behalf of all authors) Urology Division, Department of Surgery, Sardjito Hospital, Faculty of Medicine, Nursing, and Public Health, Gadjah Mada University, Yogyakarta, 55284, Indonesia","URL":"https:\/\/f1000research.com\/articles\/14-254\/v2#referee-comment-14719","order":3,"name":"referee-comment-14719","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.177664.r412958, Fakhri Taher, University of Indonesia Center for Clinical Epidemiology and Evidence Based Medicine, Jakarta, Special Capital Region of Jakarta, 07 Oct 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-254\/v1#referee-response-412958","order":4,"name":"referee-response-412958","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Erick Frapancah<\/b>; \n<i>Posted: 03 Nov 2025<\/i>; Dear reviewer,  We sincerely thank you for your constructive and insightful comments on our manuscript. We have carefully revised the paper in accordance with your suggestions. Each point has been addressed in detail below, and the corresponding changes have been incorporated into the revised version of the manuscript:  We acknowledge that our operational definition of \u201cpathological outcomes\u201d in the sentence \u201cExamined pathological outcomes, including tumour characteristics, biochemical markers, or adverse effects, in prostate cancer patients treated with subcapsular orchiectomy or medical androgen deprivation therapy (ADT)\u201d within the Study selection section may not have clearly explained the definition used in this study. We have therefore revised the sentence to read: \u201cExamined pathological outcomes including: (1) tumour characteristics (tumour stage [localized vs. metastatic], castration-resistant progression, and time to treatment failure); (2) biochemical markers (serum testosterone level and prostate-specific antigen (PSA) reduction or nadir level); and (3) adverse effects (metabolic changes such as insulin resistance, body mass index, lipid profile; haematologic effects such as anaemia or haemoglobin change; and surgical or psychological complications), in prostate cancer patients treated with subcapsular orchiectomy or medical androgen deprivation therapy (ADT).\u201d We appreciate the reviewer\u2019s observation and agree that this statement required clarification. The text has now been corrected. The screening and data extraction were performed independently by two authors (RIC and IDW). Any disagreements were resolved through discussion and consensus between these two authors; no third author was involved in these processes. We also agree that clarification was required regarding the additional publication mentioned in the Results section. This publication was identified through manual reference checking (snowballing) from the bibliographies of previously selected articles. However, we did not identify any eligible studies that were not indexed within the electronic databases included in our search strategy.  Finally, we have carefully reviewed the entire manuscript to ensure that the terminology, methodology, and descriptions are clear and consistent. We sincerely appreciate the reviewer\u2019s valuable feedback, which has significantly improved the precision, transparency, and readability of our paper. We believe that the revised version now fully addresses all reviewer comments and strengthens the overall scientific quality of the manuscript.  Respectfully, Erick Frapancah Indrawarman Soerohardjo&nbsp;(Corresponding Author) Division of Urology, Department of Surgery Faculty of Medicine, Public Health, and Nursing Universitas Gadjah Mada-Dr. Sardjito Hospital, Yogyakarta, Indonesia","URL":"https:\/\/f1000research.com\/articles\/14-254\/v2#referee-comment-14896","order":5,"name":"referee-comment-14896","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"The author(s) declared that no grants were involved in supporting this work","order":6,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}