{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T12:04:47Z","timestamp":1790597087837,"version":"4.1.0"},"reference-count":78,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T00:00:00Z","timestamp":1790294400000},"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: Androgen receptor pathway inhibitor (ARPI) intensification in metastatic hormone-sensitive prostate cancer has changed the population reaching metastatic castration-resistant prostate cancer (mCRPC), and the optimal sequence of subsequent therapies is uncertain. Methods: The study presents a narrative review of phase II\/III trials reporting radiographic progression-free survival (rPFS) or overall survival (OS) in mCRPC, including congress data, to June 2026, graded on a five-level evidence hierarchy. Results: No prospective sequencing trial has been reported. CARD (cabazitaxel versus an ARPI switch after docetaxel; OS HR 0.64) remains the clearest sequencing dataset. Alpha-controlled OS benefit for PARP inhibitors is established in the PROfound cohort A (HR 0.69) and in the TALAPRO-2 all-comer population (HR 0.80); larger BRCA-specific estimates are exploratory, and BRCA OS in TRITON3 was not improved (HR 0.91). 177Lu-PSMA-617 improved rPFS versus an ARPI switch in PSMAfore, but intention-to-treat OS did not differ (HR 0.91) amid 60% crossover; no taxane-controlled trial has shown an OS advantage, and in preliminary PLUDO data, OS favoured docetaxel first (HR 1.64), a difference potentially confounded by asymmetric crossover. Conclusions: We propose a hypothesis-generating four-track framework stratified by homologous recombination repair status and PSMA-PET expression; treatment choice remains individualised.<\/jats:p>","DOI":"10.3390\/cancers18193119","type":"journal-article","created":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:40:13Z","timestamp":1790358013000},"page":"3119","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment Sequencing in ARPI-Pre-Exposed Metastatic Castration-Resistant Prostate Cancer: Radioligand Therapy, PARP Inhibitors, and Antibody\u2013Drug Conjugates"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4368-1224","authenticated-orcid":false,"given":"Baha","family":"Sharaf","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad","family":"Al-Rwashdeh","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3697-7708","authenticated-orcid":false,"given":"Osama","family":"El Khatib","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0978-4716","authenticated-orcid":false,"given":"Akram","family":"Al-Ibraheem","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ala","family":"Abu Fara","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameen","family":"Ismail","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hadeel","family":"Alkasrawi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-4451-4625","authenticated-orcid":false,"given":"Mohamed","family":"Abdalla","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, King Hussein Cancer Center (KHCC), Amman 11941, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharif","family":"Jehad","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Yarmouk University, Irbid 21163, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,25]]},"reference":[{"key":"ref_1","first-page":"10","article-title":"Cancer Statistics, 2025","volume":"75","author":"Siegel","year":"2025","journal-title":"CA Cancer J. 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