{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T18:38:19Z","timestamp":1793126299503,"version":"4.5.0"},"reference-count":14,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"9","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["JCO Precis Oncol"],"published-print":{"date-parts":[[2025,1]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>The SPARTAN trial demonstrated that the addition of apalutamide to androgen deprivation therapy improves outcomes among patients with nonmetastatic castration-resistant prostate cancer (nmCRPC). We applied a previously reported digital histopathology\u2013based multimodal artificial intelligence (MMAI) algorithm to estimate clinical outcomes in SPARTAN.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Patients with available hematoxylin and eosin-stained slides from the primary tumor were included. Histopathology slides were digitized. MMAI scores ranging from 0 to 1 were generated from digital histopathology and baseline clinical parameters. Patients were categorized into MMAI non\u2013high-risk and high-risk groups using previously validated cutoffs. Kaplan-Meier estimates were calculated for metastasis-free survival (MFS), second progression-free survival (PFS2), and overall survival (OS); comparisons were performed using Cox proportional hazards regression for treatment arms and MMAI risk. The interaction between treatment arm and risk group was evaluated using a Cox proportional hazards model.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      The study included 420 evaluable patients after excluding those with missing clinical data or inadequate histopathology images. Of these, 63% (n = 266) were MMAI high risk and 37% (n = 154) were non\u2013high risk. MMAI risk score was associated with shorter MFS (hazard ratio [HR], 1.72;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .005), PFS2 (HR, 1.57;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .005), and OS (HR, 1.41;\n                      <jats:italic>P<\/jats:italic>\n                      = .02). MMAI high-risk patients receiving apalutamide demonstrated significant improvement in MFS (HR, 0.19;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .005), PFS2 (HR, 0.47;\n                      <jats:italic>P<\/jats:italic>\n                      &lt; .005), and OS (HR, 0.6;\n                      <jats:italic>P<\/jats:italic>\n                      = .01). The interaction between MMAI risk score and treatment for MFS (\n                      <jats:italic>P<\/jats:italic>\n                      = .01) and PFS2 (\n                      <jats:italic>P<\/jats:italic>\n                      = .03) was significant, indicating greater benefit from apalutamide treatment in MMAI high-risk patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>MMAI is a prognostic marker in nmCRPC and may serve as a predictive biomarker with high-risk patients deriving the greatest benefit from treatment with apalutamide. These results represent the first extension of an MMAI classifier to patients with castration-resistant prostate cancer, warranting additional validation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/po-24-00653","type":"journal-article","created":{"date-parts":[[2025,1,31]],"date-time":"2025-01-31T15:59:06Z","timestamp":1738339146000},"update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":14,"title":["Digital Pathology\u2013Based Multimodal Artificial Intelligence Scores and Outcomes in a Randomized Phase III Trial in Men With Nonmetastatic Castration-Resistant Prostate Cancer"],"prefix":"10.1200","clinical-trial-number":[{"clinical-trial-number":"nct01946204","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0963-7687","authenticated-orcid":true,"given":"Felix Y.","family":"Feng","sequence":"first","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthew R.","family":"Smith","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital Cancer Center, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2986-5617","authenticated-orcid":true,"given":"Fred","family":"Saad","sequence":"additional","affiliation":[{"name":"Centre Hospitalier de l'Universit\u00e9 de Montr\u00e9al, Universit\u00e9 de Montr\u00e9al, Montr\u00e9al, QC, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9310-1983","authenticated-orcid":true,"given":"Pooya","family":"Mobadersany","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaozhou K.","family":"Tian","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen S.F.","family":"Yip","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Greshock","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najat","family":"Khan","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1697-3595","authenticated-orcid":true,"given":"Margaret K.","family":"Yu","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"McCarthy","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine D.","family":"Brookman-May","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"},{"name":"LMU, University of Munich, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9838-0544","authenticated-orcid":true,"given":"Ariel B.","family":"Bourla","sequence":"additional","affiliation":[{"name":"Janssen Research &amp; Development, New Brunswick, NJ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamara","family":"Todorovic","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":"Huei-Chung","family":"Huang","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9879-1290","authenticated-orcid":true,"given":"Trevor J.","family":"Royce","sequence":"additional","affiliation":[{"name":"Artera Inc, Los Altos, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy N.","family":"Showalter","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":"Akinori","family":"Mitani","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\/0000-0003-3191-6268","authenticated-orcid":true,"given":"Eric J.","family":"Small","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"233","reference":[{"key":"e_1_3_8_2_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030452"},{"key":"e_1_3_8_3_2","unstructured":"NCCN: NCCN Clinical Practice Guidelines in Oncology Prostate Cancer. 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