{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,22]],"date-time":"2026-10-22T16:19:25Z","timestamp":1792685965016,"version":"4.5.0"},"reference-count":22,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>\n                      Radioligand therapy (RLT) with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu] Lu-PSMA-617 has shown significant benefits in metastatic castration-resistant prostate cancer (mCRPC), including prolonged overall survival (OS) and progression-free survival (PFS), as well as improved quality of life. For patients previously treated with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu]Lu-PSMA-617 who subsequently experience disease progression, retreatment with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu] Lu-PSMA-617 has emerged as a potential approach, yet data on the outcomes of RLT retreatment remains limited. This study aimed to assess the efficacy and safety of retreatment RLT in mCRPC.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Clinical and imaging data of patients who underwent at least two cycles of [\n                      <jats:sup>177<\/jats:sup>\n                      Lu] Lu-PSMA-617, followed by a second course of treatment with [\n                      <jats:sup>177<\/jats:sup>\n                      Lu] Lu-PSMA-617 between March 2018 and December 2024, were retrospectively reviewed. Endpoints included biochemical response, imaging response, toxicity, PSA-PFS, rPFS, and OS. Radiologic and biochemical responses were evaluated using RECIST 1.1 criteria and PSA levels, respectively.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      A total of 589 patients underwent [\n                      <jats:sup>177<\/jats:sup>\n                      Lu] Lu-PSMA-617 RLT, of whom 20 (3.4%, 20\/589) received RLT retreatment. The median age was 71.3 years (range: 63.7\u201395.2), and the median follow-up was 73.3 months (95% CI, 35.7\u201377.2 months) after the initial treatment and 21.7 months (95% CI, 16.9\u201326.0 months) after retreatment. The initial treatment involved a median of 4.5 cycles (range: 2\u20136). Following the first course of RLT, 15 patients (75%, 15\/20) had exhibited a &amp;gt;50% decline in PSA levels, including 9 who achieved a &amp;gt;90% decrease. Additionally, 12 patients (60%, 12\/20) had demonstrated a complete or partial imaging response, while 3 (15%, 3\/20) patients had stable disease, and 5 (25%, 5\/20) patients had progressive radiologic disease. Patients received a median of 4 retreatment cycles (range, 1\u20136), and the median interval between initial RLT and retreatment RLT was 33.1 months (IQR, 16.2\u201348.9 months; range, 10.7\u201358.8 months). A PSA decline of \u226550% was observed in 9 out of 20 patients (45%, 9\/20). An imaging response was observed in 10 patients (50%, 10\/20), with 4 achieving a complete response and 6 achieving a partial response, whereas 10 patients (50%, 10\/20) showed progression. The median PSA-PFS was 9.8 months (95% CI, 4.1\u201317.9 months), and the median rPFS was 8.2 months (95% CI, 3.3\u201317.9 months). Eight deaths occurred during follow-up. The estimated Kaplan Meier OS rates were 83.6% at 12 months (95% CI, 57.3%\u201394.4%) and 53.7% at 24 months (95% CI, 28.3%\u201373.7%). Grade 2 renal toxicity was observed in one patient (5%, 1\/20). Three patients (15%, 3\/20) developed Grade 2 anemia. Notably, no grade 3 or grade 4 adverse events were observed during either treatment period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      In our cohort, retreatment with [\u00b9\n                      <jats:sup>77<\/jats:sup>\n                      Lu]Lu-PSMA-617 RLT was associated with biochemical and imaging responses in some patients, with observed survival outcomes that support further investigation. However, given the retrospective single-arm design and small sample size, large prospective studies are needed to more rigorously evaluate the safety, efficacy, and optimal patient selection for retreatment RLT.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1831393","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T12:50:42Z","timestamp":1787921442000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["PSMA-RECAP: [177Lu]Lu-PSMA-617 retreatment in metastatic castration-resistant prostate cancer"],"prefix":"10.3389","volume":"16","author":[{"given":"Gokce","family":"Belge Bilgin","sequence":"first","affiliation":[{"name":"Department of Radiology, Mayo Clinic","place":["Rochester, MN, United 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