{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T20:00:13Z","timestamp":1785096013985,"version":"3.55.0"},"reference-count":33,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T00:00:00Z","timestamp":1785024000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Prostate"],"abstract":"ABSTRACT<\/jats:title>\n \n Introduction<\/jats:title>\n \n A subset of prostate cancer progresses to aggressive state of metastatic castration\u2010resistant prostate cancer (mCRPC), wherein multiple therapeutic options demonstrate limited success rates. In this observational study, we aimed to evaluate the efficacy, toxicity, and survival outcomes of (a) [\n 225<\/jats:sup>\n Ac]Ac\u2010PSMA\u2010617, (b) rechallenge [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617, (c) cabazitaxel, and (d) oral metronomic cyclophosphamide treatments in postdocetaxel mCRPC patients with progressive disease following initial course of [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 or without previous [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 PRLT (PSMA\u2010targeted radioligand therapy).\n <\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n The study reviewed the medical records of mCRPC patients who had documented disease progression following treatment with androgen receptor pathway inhibitors and docetaxel. These patients had multiple therapeutic options and treated with [\n 225<\/jats:sup>\n Ac]Ac\u2010PSMA\u2010617(alpha based\u2010PRLT) or rechallenge [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 or chemotherapy with cabazitaxel or metronomic cyclophosphamide. We stratified the latter group (chemotherapy) based on prior exposure to initial course of [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 as received and not received. We evaluated and analyzed the response outcomes from these therapies under five headings: (a) symptomatic response, (b) biochemical response, (c) functional and anatomical imaging response, (d) survival outcomes, and (e) toxicity profiles.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n A total 66 mCRPC patients were included and analyzed in this study. These patients were divided into two cohorts. Cohort 1 (\n n<\/jats:italic>\n \u2009=\u200949 patients) received initial course of [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 and cohort 2 (\n n<\/jats:italic>\n \u2009=\u200917 patients) not received initial course of [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617. The patients were divided into arm A to F based upon treatment received as follows: Cohort 1\u2010 arm A (\n n<\/jats:italic>\n \u2009=\u200915 patients) received [\n 225<\/jats:sup>\n Ac]Ac\u2010PSMA\u2010617, arm B (\n n<\/jats:italic>\n \u2009=\u200918 patients) received rechallenge [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617, arm C (\n n<\/jats:italic>\n \u2009=\u20098 patients) received cabazitaxel, arm D (\n n<\/jats:italic>\n \u2009=\u20098 patients) received metronomic cyclophosphamide. Cohort 2\u2010 arm E (\n n<\/jats:italic>\n \u2009=\u200914 patients) cabazitaxel and arm F (\n n<\/jats:italic>\n \u2009=\u20093 patients) metronomic cyclophosphamide. Patients in arm A showed favorable response outcomes in terms of symptomatic response evaluation and quality\u2010of\u2010life performance, biochemical and imaging response evaluation, with a PSA decline of >\u200950% and disease control rate (DCR) of 60% patients and 80% respectively. Patients treated with rechallenge [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 and chemotherapy also showed modest response rates. For toxicity profiles, arm A and arm B patients had mild and manageable toxicities, contrary to arm C, D, E, and F, wherein severe clinical and hematological toxicities were observed in a significant fraction of patients. Median progressive free survival (PFS) for the overall cohort (cohort 1 and 2) was 5 months (95% CI: 4\u20137 months), with no significant difference across treatment arms (\n p<\/jats:italic>\n \u2009=\u20090.28). Median overall survival (OS) for entire cohort was 12 months (95% CI: 9\u201315 months) with significantly longer OS in arm A and E patients compared to other arms (\n p<\/jats:italic>\n \u2009=\u20090.0358).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion<\/jats:title>\n \n Postdocetaxel mCRPC patients with progressive disease following initial course of [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 when treated with [\n 225<\/jats:sup>\n Ac]Ac\u2010PSMA\u2010617PRLT showed favorable and encouraging clinical, biochemical, and imaging response rates along with longer PFS and OS with minimal treatment\u2010related toxicities. Rechallenge [\n 177<\/jats:sup>\n Lu]Lu\u2010PSMA\u2010617 and chemotherapy\u2010based approaches also provided clinical benefit in selected patients, reflecting the range of salvage treatment strategies employed in real\u2010world practice. Future large\u2010sized, prospective randomized trials are needed to establish the efficacy of all these treatments particularly alpha\u2010based PRLT in clinical practice of mCRPC patients.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1002\/pros.70228","type":"journal-article","created":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T19:22:36Z","timestamp":1785093756000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of [\n 225<\/sup>\n Ac]Ac\u2010PSMA\u2010617 vis\u2010a\u2010vis Rechallenge [\n 177<\/sup>\n Lu]Lu\u2010PSMA\u2010617 PRLT Versus Cabazitaxel or Oral Metronomic Chemotherapy in mCRPC: An Observational Analysis of Outcome and Toxicity Profiles in a Real\u2010World Clinical Scenario"],"prefix":"10.1002","author":[{"given":"Roopal","family":"Agrawal","sequence":"first","affiliation":[{"name":"Radiation Medicine Centre, Bhabha Atomic Research Centre Tata Memorial Centre Annexe Mumbai Parel India"},{"name":"Homi Bhabha National Institute Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rahul V.","family":"Parghane","sequence":"additional","affiliation":[{"name":"Radiation Medicine Centre, Bhabha Atomic Research Centre Tata Memorial Centre Annexe Mumbai Parel India"},{"name":"Homi Bhabha National Institute Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amit","family":"Joshi","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute Mumbai India"},{"name":"Department of Medical Oncology Tata Memorial Centre Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kumar","family":"Prabhash","sequence":"additional","affiliation":[{"name":"Homi Bhabha National Institute Mumbai India"},{"name":"Department of Medical Oncology Tata Memorial Centre Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6607-2558","authenticated-orcid":false,"given":"Sandip","family":"Basu","sequence":"additional","affiliation":[{"name":"Radiation Medicine Centre, Bhabha Atomic Research Centre Tata Memorial Centre Annexe Mumbai Parel India"},{"name":"Homi Bhabha National Institute Mumbai India"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,26]]},"reference":[{"issue":"11","key":"e_1_2_15_2_1","doi-asserted-by":"crossref","first-page":"1180","DOI":"10.1111\/j.1742-1241.2011.02799.x","article-title":"Characterising the Castration\u2010Resistant Prostate Cancer Population: A Systematic Review","volume":"65","author":"Kirby M.","year":"2011","journal-title":"International Journal of Clinical Practice"},{"key":"e_1_2_15_3_1","doi-asserted-by":"crossref","first-page":"243","DOI":"10.2147\/RRU.S385257","article-title":"Metastatic Castration\u2010Resistant Prostate Cancer: Insights on Current Therapy and Promising Experimental Drugs","volume":"15","author":"Ferretti S.","year":"2023","journal-title":"Research and Reports in Urology"},{"key":"e_1_2_15_4_1","doi-asserted-by":"crossref","DOI":"10.1177\/17588359231182293","article-title":"The Current Status of Prostate Cancer Treatment and PSMA Theranostics","volume":"15","author":"Uemura M.","year":"2023","journal-title":"Therapeutic Advances in Medical Oncology"},{"key":"e_1_2_15_5_1","doi-asserted-by":"crossref","DOI":"10.3389\/fmed.2021.692436","article-title":"Revisiting the Radiobiology of Targeted Alpha Therapy","volume":"8","author":"Pouget J. 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[177Lu]Lu\u2010PSMA\u2010617 Versus Cabazitaxel in Patients With Metastatic Castration\u2010Resistant Prostate Cancer (TheraP): A Randomised, Open\u2010Label, Phase 2 Trial","volume":"397","author":"Hofman M. S.","year":"2021","journal-title":"Lancet"},{"key":"e_1_2_15_20_1","doi-asserted-by":"crossref","first-page":"4520","DOI":"10.1007\/s12325-021-01823-6","article-title":"Real\u2010World Treatment Patterns and Overall Survival of Patients With Metastatic Castration\u2010Resistant Prostate Cancer in the US Prior to PARP Inhibitors","volume":"38","author":"Shore N. D.","year":"2021","journal-title":"Advances in Therapy"},{"issue":"2","key":"e_1_2_15_21_1","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1007\/s00432-023-05525-0","article-title":"Metronomic Cyclophosphamide for Bone Marrow Carcinomatosis in Metastatic Castration\u2010Resistant Prostate Cancer","volume":"150","author":"Peres T.","year":"2024","journal-title":"Journal of Cancer Research and Clinical Oncology"},{"key":"e_1_2_15_22_1","doi-asserted-by":"publisher","DOI":"10.1200\/GO-24-00464"},{"issue":"12","key":"e_1_2_15_23_1","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1056\/NEJMoa2107322","article-title":"Lutetium\u2010177\u2013PSMA\u2010617 for Metastatic Castration\u2010Resistant Prostate Cancer","volume":"385","author":"Sartor O.","year":"2021","journal-title":"New England Journal of Medicine"},{"issue":"13","key":"e_1_2_15_24_1","doi-asserted-by":"crossref","first-page":"4151","DOI":"10.1007\/s00259-024-06825-4","article-title":"Efficacy and Safety of Rechallenge [177Lu]Lu\u2010PSMA\u2010617 RLT After Initial Partial Remission in Patients With mCRPC: Evaluation of a Prospective Registry (REALITY Study)","volume":"51","author":"Rosar F.","year":"2024","journal-title":"European Journal of Nuclear Medicine and Molecular Imaging"},{"issue":"3","key":"e_1_2_15_25_1","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1097\/RLU.0000000000005589","article-title":"Re\u2010Rechallenge 177Lu\u2010PSMA\u2010617 Radioligand Therapy in Metastatic Castration\u2010Resistant Prostate Cancer: A Step Further","volume":"50","author":"Aggarwal P.","year":"2025","journal-title":"Clinical Nuclear Medicine"},{"issue":"3","key":"e_1_2_15_26_1","doi-asserted-by":"crossref","first-page":"343","DOI":"10.1016\/j.eururo.2020.11.013","article-title":"Activity and Adverse Events of Actinium\u2010225\u2010PSMA\u2010617 in Advanced Metastatic Castration\u2010Resistant Prostate Cancer After Failure of Lutetium\u2010177\u2010Psma","volume":"79","author":"Feuerecker B.","year":"2021","journal-title":"European Urology"},{"issue":"10","key":"e_1_2_15_27_1","doi-asserted-by":"crossref","first-page":"1574","DOI":"10.2967\/jnumed.123.265546","article-title":"Clinical Experience With [225Ac]Ac\u2010PSMA Treatment in Patients With [177Lu]Lu\u2010PSMA\u2010Refractory Metastatic Castration\u2010Resistant Prostate Cancer","volume":"64","author":"Alan\u2010Selcuk N.","year":"2023","journal-title":"Journal of Nuclear Medicine"},{"issue":"16","key":"e_1_2_15_28_1","doi-asserted-by":"crossref","first-page":"5010","DOI":"10.1200\/JCO.2026.44.16_suppl.5010","article-title":"AcTION: Phase 1 Study of [225Ac]Ac\u2010PSMA\u2010617 (225Ac\u2010PSMA\u2010617) in Men With Metastatic Castration\u2010Resistant Prostate Cancer (mCRPC) With or Without Prior [177Lu]Lu\u2010PSMA (177Lu\u2010PSMA) Radioligand Therapy (RLT)","volume":"44","author":"Emmett L.","year":"2026","journal-title":"Journal of Clinical Oncology"},{"issue":"20","key":"e_1_2_15_29_1","doi-asserted-by":"crossref","first-page":"9364","DOI":"10.7150\/thno.48107","article-title":"Efficacy and Safety of 225Ac\u2010PSMA\u2010617 Targeted Alpha Therapy in Metastatic Castration\u2010Resistant Prostate Cancer Patients","volume":"10","author":"Yadav M. 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