{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T09:16:11Z","timestamp":1783329371623,"version":"3.54.6"},"reference-count":39,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,5]],"date-time":"2026-07-05T00:00:00Z","timestamp":1783209600000},"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>Lutetium-177-PSMA-617 (Lu-PSMA) radioligand therapy (RLT) is established in metastatic castration-resistant prostate cancer (mCRPC), with regulatory approvals based on the VISION and TheraP trials. Subsequent trials have extended the evidence to taxane-naive mCRPC (PSMAfore) and demonstrated that combining Lu-PSMA with enzalutamide yields a significant overall survival benefit over enzalutamide alone (ENZA-p). However, higher and more homogeneous PSMA expression in treatment-naive disease, combined with lower tumor burden and preserved bone marrow reserve, provides a biological rationale for deploying RLT earlier in the disease course. In metastatic hormone-sensitive prostate cancer (mHSPC), the Phase III PSMAddition trial reported improved radiographic progression-free survival when Lu-PSMA was added to standard androgen deprivation therapy (ADT) plus androgen receptor pathway inhibitor (ARPI), and the Phase II UpFrontPSMA trial demonstrated enhanced biochemical responses with Lu-PSMA induction before docetaxel. In oligometastatic and oligorecurrent disease, the BULLSEYE and LUNAR trials have shown progression-free survival benefits, raising the possibility of deferring androgen deprivation therapy and its associated morbidity. Meanwhile, next-generation radionuclides, including actinium-225 (WARMTH) and the dual beta-Auger emitter terbium-161 (VIOLET), are entering clinical development to address the radiobiological limitations of Lutetium-177. This review synthesizes the evidence for PSMA-targeted radioligand therapy across the prostate cancer disease continuum and discusses patient selection, treatment sequencing, and the access and cost-effectiveness considerations that will shape adoption in earlier disease settings.<\/jats:p>","DOI":"10.3390\/cancers18132161","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T08:05:38Z","timestamp":1783325138000},"page":"2161","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["PSMA-Targeted Radioligand Therapy Beyond the Post-Taxane Setting: A Review of Evidence Across the Prostate Cancer Spectrum"],"prefix":"10.3390","volume":"18","author":[{"given":"Kaiying","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Urology, National University Hospital, Singapore 119074, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daanesh Huned","family":"Hassanbhai","sequence":"additional","affiliation":[{"name":"Department of Urology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roxanne Yong Ai","family":"Teo","sequence":"additional","affiliation":[{"name":"Department of Urology, Tan Tock Seng Hospital, Singapore 308433, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chloe Shu Hui","family":"Ong","sequence":"additional","affiliation":[{"name":"Department of Urology, National University Hospital, Singapore 119074, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kah Wai","family":"Lai","sequence":"additional","affiliation":[{"name":"Department of Urology, National University Hospital, Singapore 119074, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Xuan","family":"Koo","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine and Molecular Imaging, Singapore General Hospital, Singapore 169608, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Loon","family":"Yam","sequence":"additional","affiliation":[{"name":"Department of Urology, Changi General Hospital, Singapore 529889, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4991-9790","authenticated-orcid":false,"given":"Joshua Yi Min","family":"Tung","sequence":"additional","affiliation":[{"name":"Department of Urology, Changi General Hospital, Singapore 529889, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"528","DOI":"10.1002\/jcb.10661","article-title":"Tumor target prostate specific membrane antigen (PSMA) and its regulation in prostate cancer","volume":"91","author":"Ghosh","year":"2004","journal-title":"J. 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