{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T07:46:31Z","timestamp":1790754391542,"version":"4.1.0"},"reference-count":39,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2025,10,22]],"date-time":"2025-10-22T00:00:00Z","timestamp":1761091200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,11,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>177Lu-PSMA-617 is approved for patients with metastatic castration-resistant prostate cancer (mCRPC). Although treatment is associated with improved outcomes, not all patients benefit and response is heterogeneous. We aim to characterize genomic alterations associated with benefit to 177Lu-PSMA-617.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>This study used the Prostate Cancer Precision Medicine Multi-Institutional Collaborative Effort (PROMISE) clinical-genomic database (n\u2009=\u20092445). The primary endpoint was \u226550% PSA decline (PSA50) from baseline with 177Lu-PSMA-617 in molecular subgroups. Secondary endpoints included 90% PSA decline (PSA90). Associations were assessed using Fisher\u2019s exact test and Cox regression in multivariable analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We identified 183 mCRPC patients treated with 177Lu-PSMA-617. Median number of prior lines of mCRPC therapy was 3. Overall, PSA50 was 49%, median progression-free survival was 7.6\u2009months, and median overall survival was 13.9\u2009months. NF1 (n\u2009=\u20098) and FOXA1 alterations (n\u2009=\u20095) were associated with increased PSA50 (88% vs 47%, P\u2009=\u2009.03 for NF1; 100% vs 47%, P\u2009=\u2009.03 for FOXA1). Among CRPC sequenced tumors (n\u2009=\u2009119), androgen receptor (AR) alterations (n\u2009=\u200958) were associated with lower PSA50 (38% vs 60%, P\u2009=\u2009.03). While any tumor suppressor genes (TSG) (PTEN, TP53, RB1) (n\u2009=\u2009109) or TP53 (n\u2009=\u200983) alteration were associated with lower PSA90 (P\u2009=\u2009.02 for both), NF1 (n\u2009=\u20098), and FOXA1 alterations were associated with higher PSA90 (P\u2009=\u2009.03 and P\u2009=\u2009.003, respectively).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>This analysis identifies potential genomic predictors of response to 177Lu-PSMA-617, with NF1 and FOXA1 alterations associated with favorable outcomes and AR and TSG alterations with diminished response. These hypothesis-generating findings suggest genomic profiling may inform selection for PSMA-targeted therapy and warrant prospective validation in larger cohorts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf358","type":"journal-article","created":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T11:42:46Z","timestamp":1760787766000},"source":"Crossref","is-referenced-by-count":7,"title":["Genomic alterations and associated outcomes in patients with PSMA-positive metastatic castration-resistant prostate cancer treated with 177Lu-PSMA-617"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6651-195X","authenticated-orcid":false,"given":"Justine","family":"Panian","sequence":"first","affiliation":[{"name":"University of California San Diego, Department of Medicine , San Diego, CA 92037,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas C","family":"Henderson","sequence":"additional","affiliation":[{"name":"University of Michigan, Department of Medicine , Ann Arbor, MI 48109,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5166-848X","authenticated-orcid":false,"given":"Daniel","family":"Herchenhorn","sequence":"additional","affiliation":[{"name":"University of California San Diego, Department of Medicine , San Diego, CA 92037,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8890-2951","authenticated-orcid":false,"given":"Pedro C","family":"Barata","sequence":"additional","affiliation":[{"name":"University Hospitals Seidman Cancer Center, Department of Medicine , Cleveland, OH 44106,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mehmet Asim","family":"Bilen","sequence":"additional","affiliation":[{"name":"Winship Cancer Institute of Emory University, Department of Medicine , Atlanta, GA 30322,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura","family":"Graham","sequence":"additional","affiliation":[{"name":"University of Colorado Anschutz Medical Campus, Department of Medicine , Aurora, CO 80045,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elisabeth","family":"Heath","sequence":"additional","affiliation":[{"name":"Wayne State University, Department of Medicine , Detroit, MI 48201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clara","family":"Hwang","sequence":"additional","affiliation":[{"name":"Henry Ford Health System, Department of Medicine , Detroit, MI 49201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Avery","family":"Supernois","sequence":"additional","affiliation":[{"name":"Henry Ford Health System, Department of Medicine , Detroit, MI 49201,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deepak","family":"Kilari","sequence":"additional","affiliation":[{"name":"Medical College of Wisconsin, Department of Medicine , Milwaukee, WI 53226,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bicky","family":"Thapa","sequence":"additional","affiliation":[{"name":"Dana-Farber Cancer Institute, Department of Medicine , Boston, MA 02215,","place":["United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2277-8668","authenticated-orcid":false,"given":"Vadim S","family":"Koshkin","sequence":"additional","affiliation":[{"name":"University of California San Francisco, Department of Medicine , San Francisco, CA 94143,","place":["United 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