{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T09:18:33Z","timestamp":1783070313315,"version":"3.54.6"},"reference-count":35,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background\/Objectives: Treatment intensification with novel hormonal therapies is now standard in metastatic hormone-sensitive prostate cancer (mHSPC), but real-world patients are often more heterogeneous than those included in pivotal trials. This study aimed to describe clinical characteristics, safety, treatment discontinuation, disease progression, polypharmacy, and clinically documented drug\u2013drug interactions in a real-world mHSPC cohort. Methods: We conducted a retrospective observational study including 109 patients with mHSPC who initiated abiraterone, enzalutamide, apalutamide, or docetaxel-based triplet regimens between January 2015 and November 2025. Outcomes included adverse events, discontinuation, PSA50 response at 3 months, time to progression and overall survival. Descriptive analyses and Kaplan\u2013Meier estimates were performed. Results: Apalutamide was the most frequent first-line treatment (56.9%), followed by abiraterone (23.9%), enzalutamide (11.9%), darolutamide-based triplet therapy (3.7%), and abiraterone-based triplet therapy (3.7%). Median age was 73 years, and median baseline PSA was 16.1 ng\/mL. De novo metastatic disease was present in 69.7% of patients, ISUP grade 4\u20135 disease in 58.7%, high-risk disease according to LATITUDE criteria in 45.9%, and high-volume disease according to CHAARTED criteria in 38.5%. The median Charlson Comorbidity Index was 4, and polypharmacy was observed in 68.8%. Adverse events occurred in 56.0%, and non-death treatment discontinuation occurred in 22.0%. No documented drug\u2013drug interactions requiring treatment modification were recorded. PSA50 response was achieved by 97.2%. Thirteen patients (11.9%) progressed and 18 (16.5%) died. Median time to progression was not reached, and median overall survival was 53.2 months. Conclusions: Novel hormonal therapies were used in a clinically heterogeneous real-world mHSPC cohort. The findings support individualized treatment assessment and should be interpreted as descriptive and exploratory.<\/jats:p>","DOI":"10.3390\/cancers18132144","type":"journal-article","created":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T07:59:47Z","timestamp":1783065587000},"page":"2144","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Safety and Treatment Discontinuation of Novel Hormonal Therapies in Metastatic Hormone-Sensitive Prostate Cancer: An Exploratory Real-World Study"],"prefix":"10.3390","volume":"18","author":[{"given":"Irene","family":"Millan-Ramos","sequence":"first","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alberto","family":"Zambudio-Munuera","sequence":"additional","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Herraez-Marcos","sequence":"additional","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Jimenez-Pacheco","sequence":"additional","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francisco","family":"Gutierrez-Tejero","sequence":"additional","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel","family":"Arrabal-Martin","sequence":"additional","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"},{"name":"Instituto Investigaci\u00f3n Biosanitaria de Granada (IBS), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miguel Angel","family":"Arrabal-Polo","sequence":"additional","affiliation":[{"name":"Urology Department, San Cecilio University Hospital, 18016 Granada, Spain"},{"name":"Instituto Investigaci\u00f3n Biosanitaria de Granada (IBS), 18012 Granada, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1056\/NEJMoa1503747","article-title":"Chemohormonal Therapy in Metastatic Hormone-Sensitive Prostate Cancer","volume":"373","author":"Sweeney","year":"2015","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"352","DOI":"10.1056\/NEJMoa1704174","article-title":"Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer","volume":"377","author":"Fizazi","year":"2017","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1056\/NEJMoa1903835","article-title":"Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer","volume":"381","author":"Davis","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1056\/NEJMoa1903307","article-title":"Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer","volume":"381","author":"Chi","year":"2019","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1695","DOI":"10.1016\/S0140-6736(22)00367-1","article-title":"Abiraterone plus Prednisone Added to Androgen Deprivation Therapy and Docetaxel in de Novo Metastatic Castration-Sensitive Prostate Cancer (PEACE-1): A Multicentre, Open-Label, Randomised, Phase 3 Study with a 2 \u00d7 2 Factorial Design","volume":"399","author":"Fizazi","year":"2022","journal-title":"Lancet"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1132","DOI":"10.1056\/NEJMoa2119115","article-title":"Darolutamide and Survival in Metastatic, Hormone-Sensitive Prostate Cancer","volume":"386","author":"Smith","year":"2022","journal-title":"N. Engl. J. Med."},{"key":"ref_7","unstructured":"(2026, May 24). EAU Guidelines on Prostate Cancer\u2014TREATMENT. Uroweb. Available online: https:\/\/uroweb.org\/guidelines\/prostate-cancer\/chapter\/treatment?utm_source=chatgpt.com."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1119","DOI":"10.1016\/j.annonc.2020.06.011","article-title":"Prostate Cancer: ESMO Clinical Practice Guidelines for Diagnosis, Treatment and Follow-Up","volume":"31","author":"Parker","year":"2020","journal-title":"Ann. Oncol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s40261-020-00888-5","article-title":"Systemic Treatment for Metastatic Hormone Sensitive Prostate Cancer: A Comprehensive Meta-Analysis Evaluating Efficacy and Safety in Specific Sub-Groups of Patients","volume":"40","author":"Santoni","year":"2020","journal-title":"Clin. Drug Investig."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"408","DOI":"10.1111\/bju.16577","article-title":"Real-world Use of Androgen-deprivation Therapy Intensification for Metastatic Hormone-sensitive Prostate Cancer: A Systematic Review","volume":"135","author":"Raval","year":"2025","journal-title":"BJU Int."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1080\/17425255.2024.2353749","article-title":"New-Generation Androgen Receptor Signaling Inhibitors (ARSIs) in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Pharmacokinetics, Drug-Drug Interactions (DDIs), and Clinical Impact","volume":"20","author":"Gasperoni","year":"2024","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1002\/pros.24813","article-title":"Comparison of Abiraterone, Enzalutamide, and Apalutamide for Metastatic Hormone-sensitive Prostate Cancer: A Multicenter Study","volume":"85","author":"Yanagisawa","year":"2025","journal-title":"Prostate"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Von Elm, E., Altman, D.G., Egger, M., Pocock, S.J., G\u00f8tzsche, P.C., Vandenbroucke, J.P., and for the STROBE Initiative (2007). The Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: Guidelines for Reporting Observational Studies. PLoS Med., 4.","DOI":"10.1371\/journal.pmed.0040296"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Benchimol, E.I., Smeeth, L., Guttmann, A., Harron, K., Moher, D., Petersen, I., S\u00f8rensen, H.T., Von Elm, E., Langan, S.M., and RECORD Working Committee (2015). The REporting of Studies Conducted Using Observational Routinely-Collected Health Data (RECORD) Statement. PLoS Med., 12.","DOI":"10.1371\/journal.pmed.1001885"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1174","DOI":"10.1200\/OP-24-00690","article-title":"Real-World Evidence of Combination Therapy Use in Metastatic Hormone-Sensitive Prostate Cancer in the United States From 2017 to 2023","volume":"21","author":"Raval","year":"2025","journal-title":"JCO Oncol. Pract."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"e259433","DOI":"10.1001\/jamanetworkopen.2025.9433","article-title":"Treatment Patterns and Survival Among Veterans With De Novo Metastatic Hormone-Sensitive Prostate Cancer","volume":"8","author":"Schoen","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1016\/j.euo.2023.05.002","article-title":"Does Research from Clinical Trials in Metastatic Hormone-Sensitive Prostate Cancer Treatment Translate into Access to Treatments for Patients in the \u201cReal World\u201d? A Systematic Review","volume":"7","author":"Dodkins","year":"2024","journal-title":"Eur. Urol. Oncol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/j.euros.2025.09.010","article-title":"Real-World Evidence on Baseline Characteristics and Treatment in Metastatic Hormone-Sensitive Prostate Cancer: Findings from the PIONEER 2.0 Big Data Investigation Group","volume":"81","author":"Rivas","year":"2025","journal-title":"Eur. Urol. Open Sci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"625","DOI":"10.1080\/17425255.2025.2478167","article-title":"Drug-Drug Interactions in Metastatic Hormone-Sensitive Prostate Cancer (mHSPC): Practical Considerations for Treating Men with Androgen Receptor Pathway Inhibitors and Common Medications in This Stage","volume":"21","author":"Montesa","year":"2025","journal-title":"Expert Opin. Drug Metab. Toxicol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"325","DOI":"10.1080\/14737140.2024.2328778","article-title":"Drug\u2013Drug Interaction Potential among Patients with Nonmetastatic Castration-Resistant Prostate Cancer (nmCRPC) Treated with Novel Androgen Receptor Inhibitors","volume":"24","author":"Appukkuttan","year":"2024","journal-title":"Expert Rev. Anticancer Ther."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Leblanc, K., Edwards, S.J., Dranitsaris, G., Leong, D.P., Carrier, M., Malone, S., Rendon, R.A., Bond, A.M., Sitland, T.D., and Zalewski, P. (2024). Drug Interactions between Androgen Receptor Axis-Targeted Therapies and Antithrombotic Therapies in Prostate Cancer: Delphi Consensus. Cancers, 16.","DOI":"10.3390\/cancers16193336"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1080\/14796694.2025.2481024","article-title":"Contemporary Real-World Treatment in Metastatic Hormone-Sensitive Prostate Cancer: US, Four European Countries, and UK","volume":"21","author":"Goebell","year":"2025","journal-title":"Future Oncol."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"926","DOI":"10.1016\/j.euf.2025.08.005","article-title":"Observational Health Data Analysis of the Cardiovascular Adverse Events of Systemic Treatment in Patients with Metastatic Hormone-Sensitive Prostate Cancer: Big Data Analytics Using the PIONEER Platform","volume":"11","author":"Rajwa","year":"2025","journal-title":"Eur. Urol. Focus"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"hyag042","DOI":"10.1093\/jjco\/hyag042","article-title":"Real-World Comparison of Enzalutamide and Apalutamide in Metastatic Hormone-Sensitive Prostate Cancer: A Multi-Institutional Propensity Score-Matched Analysis","volume":"56","author":"Nishimura","year":"2026","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1016\/j.clgc.2023.12.018","article-title":"Real-World Evidence of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer: An Austrian Multicenter Study","volume":"22","author":"Kafka","year":"2024","journal-title":"Clin. Genitourin. Cancer"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1198","DOI":"10.1002\/pros.24755","article-title":"Real-world Study: Impact of Multidisciplinary Management of Apalutamide-associated Adverse Events in Prostate Cancer","volume":"84","author":"Gil","year":"2024","journal-title":"Prostate"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1093\/jjco\/hyad143","article-title":"Real-World Prostate-Specific Antigen Response and Progression to Castration-Resistant Prostate Cancer among Men with Metastatic Castration-Sensitive Prostate Cancer Treated with Apalutamide: A Multi-Institutional Study in the Chu-Shikoku Japan Urological Consortium","volume":"54","author":"Tohi","year":"2024","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1701","DOI":"10.1007\/s11096-025-01920-4","article-title":"Real-World Clinical Outcomes of Apalutamide versus Abiraterone with Androgen Deprivation Therapy for Metastatic Hormone-Sensitive Prostate Cancer","volume":"47","year":"2025","journal-title":"Int. J. Clin. Pharm."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"B\u00fcttner, T., Rizzo, M., Bernal Vaca, L., Molina-Cerrillo, J., Alonso-Gordoa, T., Ju\u00e1rez, A., Buchler, T., Seront, E., Kucharz, J., and Gandur Quiroga, M.N. (2026). Enzalutamide in Metastatic Hormone-Sensitive Prostate Cancer: Results from the International, Multicentre, Real-World ARON-3 Study. Prostate Cancer Prostatic Dis., 1\u20137.","DOI":"10.1038\/s41391-025-01067-3"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1016\/j.euo.2024.11.005","article-title":"Apalutamide in Metastatic Castration-Sensitive Prostate Cancer: Results from the Multicenter Real-World ARON-3 Study","volume":"8","author":"Santoni","year":"2025","journal-title":"Eur. Urol. Oncol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"3543","DOI":"10.1007\/s11255-025-04465-7","article-title":"Short-Term Outcomes of Triplet Therapy in Metastatic Hormone-Sensitive Prostate Cancer in Older Adults: A Retrospective, Single-Center Real-World Cohort Study","volume":"57","author":"Usui","year":"2025","journal-title":"Int. Urol. Nephrol."},{"key":"ref_32","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios (AEMPS) (2026, June 18). Informe de Posicionamiento Terap\u00e9utico de Abiraterona (Zytiga\u00ae) en Combinaci\u00f3n con Tratamiento de Deprivaci\u00f3n de Andr\u00f3genos en C\u00e1ncer de Pr\u00f3stata Hormonosensible Metast\u00e1sico de Nuevo Diagn\u00f3stico. IPT, 8\/2020. V1. Fecha de publicaci\u00f3n: 4 de mayo de 2020, Available online: https:\/\/www.aemps.gob.es\/medicamentosUsoHumano\/informesPublicos\/docs\/IPT_8-2020-abiraterona-Zytig.pdf."},{"key":"ref_33","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios (AEMPS) (2026, June 18). Informe de Posicionamiento Terap\u00e9utico de Apalutamida (Erleada\u00ae) en Combinaci\u00f3n con Tratamiento de Privaci\u00f3n de Andr\u00f3genos en C\u00e1ncer de Pr\u00f3stata Hormonosensible Metast\u00e1sico. IPT, 4\/2021. V1. Fecha de publicaci\u00f3n: 8 de marzo de 2021, Available online: https:\/\/www.aemps.gob.es\/medicamentosUsoHumano\/informesPublicos\/docs\/2021\/IPT_4-2021-Erleada.pdf."},{"key":"ref_34","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios (AEMPS) (2026, June 18). Informe de Posicionamiento Terap\u00e9utico de Enzalu-Tamida (Xtandi\u00ae) en Combinaci\u00f3n con la Terapia de Privaci\u00f3n Androg\u00e9nica (TPA) en el Tratamiento del C\u00e1ncer de Pr\u00f3stata Hormonosensible Metast\u00e1sico (CPHSm). IPT, 19\/2022. V1. Fecha de actualizaci\u00f3n: 25 de febrero de 2022, Available online: https:\/\/www.aemps.gob.es\/medicamentosUsoHumano\/informesPublicos\/docs\/2022\/IPT_19-2022-Xtandi.pdf."},{"key":"ref_35","unstructured":"Agencia Espa\u00f1ola de Medicamentos y Productos Sanitarios (AEMPS) (2026, June 18). Informe de Posicionamiento Terap\u00e9utico de Darolu-Tamida (Nubeqa\u00ae) en Combinaci\u00f3n con Docetaxel y Terapia de Privaci\u00f3n Androg\u00e9nica en C\u00e1ncer de Pr\u00f3stata Hormonosensible Metast\u00e1sico. IPT-232\/V1\/08022024, Available online: https:\/\/www.aemps.gob.es\/medicamentosUsoHumano\/informesPublicos\/docs\/2024\/IPT-232-Nubeqa-darolutamida.pdf."}],"container-title":["Cancers"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2144\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T08:45:52Z","timestamp":1783068352000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6694\/18\/13\/2144"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,3]]},"references-count":35,"journal-issue":{"issue":"13","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["cancers18132144"],"URL":"https:\/\/doi.org\/10.3390\/cancers18132144","relation":{},"ISSN":["2072-6694"],"issn-type":[{"value":"2072-6694","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,3]]}}}