{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T14:35:03Z","timestamp":1791470103874,"version":"4.3.4"},"reference-count":17,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"32","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,11,10]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Long-term androgen deprivation therapy (ADT) improves survival in men with high-risk localized prostate cancer (PCa) receiving radiotherapy (RT). Predictive biomarkers are needed to guide ADT duration.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>A multimodal artificial intelligence (MMAI)\u2013derived predictive biomarker was trained for long-term (LT) versus short-term (ST) ADT using pretreatment digital prostate biopsy images and clinical data (age, prostate-specific antigen, Gleason, and T stage) from six NRG Oncology phase III randomized radiotherapy trials. The novel MMAI-derived biomarker was developed to predict the differential benefit of LT-ADT on the primary end point, distant metastasis (DM). MMAI predictive utility was validated on a seventh randomized trial, RTOG 9202 (N = 1,192), which randomly assigned men to RT + ST-ADT (4 months) versus RT + LT-ADT (28 months). Fine-Gray and cumulative incidence analyses for DM, and secondarily, death with DM, were performed. Deaths without DM were treated as competing risks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      In the validation cohort (median follow-up, 17.2 years), LT-ADT significantly improved DM from 26% to 17% (subdistribution hazard ratio [sHR], 0.64 [95% CI, 0.50 to 0.82],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001). A significant biomarker-treatment predictive interaction was observed (\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .04) for DM, whereby MMAI biomarker\u2013positive men (n = 785, 66%) had reduced DM with LT-ADT versus ST-ADT (sHR, 0.55 [95% CI, 0.41 to 0.73],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001), whereas no treatment benefit was observed for MMAI biomarker\u2013negative men (n = 407; sHR, 1.06 [95% CI, 0.61 to 1.84],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .84). The estimated 15-year DM risk difference between RT + LT-ADT and RT + ST-ADT was 14% in MMAI biomarker\u2013positive men and 0% in MMAI biomarker\u2013negative men. The MMAI biomarker was also prognostic for DM, irrespective of treatment (sHR, 2.35 [95% CI, 1.72 to 3.19],\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      &lt; .001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>To our knowledge, the MMAI model is the first validated predictive biomarker to guide ADT duration with RT in localized\/locally advanced PCa. Approximately one third of men with high-risk PCa could safely be spared the additional 24 months of ADT and the associated morbidity.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco.24.00365","type":"journal-article","created":{"date-parts":[[2025,4,16]],"date-time":"2025-04-16T15:59:12Z","timestamp":1744819152000},"page":"3494-3504","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":30,"title":["Development and Validation of an Artificial Intelligence Digital Pathology Biomarker to Predict Benefit of Long-Term Hormonal Therapy and Radiotherapy in Men With High-Risk Prostate Cancer Across Multiple Phase III Trials"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct00767286","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7012-1754","authenticated-orcid":true,"given":"Andrew J.","family":"Armstrong","sequence":"first","affiliation":[{"name":"Duke University Medical Center, Durham, NC"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7152-6830","authenticated-orcid":true,"given":"Vinnie Y.T.","family":"Liu","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ramprasaath R.","family":"Selvaraju","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmalyn","family":"Chen","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffry P.","family":"Simko","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandy","family":"DeVries","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8777-7343","authenticated-orcid":false,"given":"Oliver","family":"Sartor","sequence":"additional","affiliation":[{"name":"Mayo Clinic, Rochester, MN"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8193-5769","authenticated-orcid":true,"given":"Howard M.","family":"Sandler","sequence":"additional","affiliation":[{"name":"Cedars-Sinai Medical Center, Los Angeles, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2972-657X","authenticated-orcid":true,"given":"Osama","family":"Mohamad","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huei-Chung","family":"Huang","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Griffin","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rikiya","family":"Yamashita","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andre","family":"Esteva","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0147-0376","authenticated-orcid":true,"given":"Phuoc T.","family":"Tran","sequence":"additional","affiliation":[{"name":"University of Maryland, Baltimore, MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5973-4741","authenticated-orcid":true,"given":"Daniel E.","family":"Spratt","sequence":"additional","affiliation":[{"name":"Case Western Reserve University, Cleveland, OH"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John Hi","family":"Carson","sequence":"additional","affiliation":[{"name":"Saint John Regional Hospital, Saint John, New Brunswick, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Peters","sequence":"additional","affiliation":[{"name":"Northeast Radiation Oncology Center, Dunmore, PA accrual for Regional Hospital of Scranton"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elizabeth","family":"Gore","sequence":"additional","affiliation":[{"name":"Zablocki Veterans Administration Medical Center, Milwaukee, WI"},{"name":"Medical College of Wisconsin, Milwaukee, WI, Accrual for Clarkson Hospital"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7168-1542","authenticated-orcid":false,"given":"Steve P.","family":"Lee","sequence":"additional","affiliation":[{"name":"Long Beach VA Healthcare System, Long Beach, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jedidiah M.","family":"Monson","sequence":"additional","affiliation":[{"name":"Saint Agnes Medical Center, Fresno, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark E.","family":"Augspurger","sequence":"additional","affiliation":[{"name":"Baptist Medical Center South, Jacksonville, FL"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4581-2892","authenticated-orcid":true,"given":"Ali","family":"El-Gayed","sequence":"additional","affiliation":[{"name":"Saskatoon Cancer Centre, Saskatoon, SK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph P.","family":"Rodgers","sequence":"additional","affiliation":[{"name":"NRG Oncology Statistics and Data Management Center, Philadelphia, PA"},{"name":"American College of Radiology, Philadelphia, PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0581-7963","authenticated-orcid":true,"given":"Rana","family":"McKay","sequence":"additional","affiliation":[{"name":"University of California San Diego Moores Cancer Center, La Jolla, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1140-0603","authenticated-orcid":true,"given":"Todd","family":"Morgan","sequence":"additional","affiliation":[{"name":"University of Michigan, Ann Arbor, MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-7687","authenticated-orcid":true,"given":"Felix Y.","family":"Feng","sequence":"additional","affiliation":[{"name":"University of California San Francisco, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul L.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"Brigham and Women's Hospital, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_9_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00705-1"},{"key":"e_1_3_9_3_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.09.3369"},{"key":"e_1_3_9_4_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2595"},{"key":"e_1_3_9_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.3662"},{"key":"e_1_3_9_6_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41746-022-00613-w"},{"key":"e_1_3_9_7_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2022.40.16_suppl.108"},{"key":"e_1_3_9_8_2","doi-asserted-by":"publisher","DOI":"10.1056\/EVIDoa2300023"},{"key":"e_1_3_9_9_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2003.05.004"},{"key":"e_1_3_9_10_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2014.58.0662"},{"key":"e_1_3_9_11_2","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.0039"},{"key":"e_1_3_9_12_2","doi-asserted-by":"publisher","DOI":"10.3816\/CGC.2005.n.035"},{"key":"e_1_3_9_13_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2021.08.031"},{"key":"e_1_3_9_14_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2017.02.004"},{"key":"e_1_3_9_15_2","doi-asserted-by":"crossref","first-page":"e078378","DOI":"10.1136\/bmj-2023-078378","article-title":"TRIPOD+AI statement: Updated guidance for reporting clinical prediction models that use regression or machine learning methods","volume":"385","author":"Collins GS","year":"2024","unstructured":"Collins GS, Moons KGM, Dhiman P, et al: TRIPOD+AI statement: Updated guidance for reporting clinical prediction models that use regression or machine learning methods. BMJ 385:e078378, 2024","journal-title":"BMJ"},{"key":"e_1_3_9_16_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0810095"},{"key":"e_1_3_9_17_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.13.9881"},{"key":"e_1_3_9_18_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2006.06.2497"}],"container-title":["Journal of Clinical Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/ascopubs.org\/doi\/pdfdirect\/10.1200\/JCO.24.00365","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T22:59:27Z","timestamp":1762383567000},"score":1,"resource":{"primary":{"URL":"https:\/\/ascopubs.org\/doi\/10.1200\/JCO.24.00365"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,11,10]]},"references-count":17,"journal-issue":{"issue":"32","published-print":{"date-parts":[[2025,11,10]]}},"alternative-id":["10.1200\/JCO.24.00365"],"URL":"https:\/\/doi.org\/10.1200\/jco.24.00365","relation":{},"ISSN":["0732-183X","1527-7755"],"issn-type":[{"value":"0732-183X","type":"print"},{"value":"1527-7755","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,11,10]]},"assertion":[{"value":"2024-03-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-10","order":1,"name":"revised","label":"Revised","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-02-12","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}