{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T02:49:28Z","timestamp":1791427768468,"version":"4.3.3"},"reference-count":24,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:00Z","timestamp":1791331200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Int J of Urology"],"published-print":{"date-parts":[[2026,10]]},"abstract":"ABSTRACT<\/jats:title>\n \n Objectives<\/jats:title>\n To evaluate treatment\u2010effect heterogeneity associated with local therapy in nonmetastatic advanced prostate cancer and develop a simple hypothesis\u2010generating framework to estimate the expected absolute survival benefit associated with local therapy.<\/jats:p>\n <\/jats:sec>\n \n Methods<\/jats:title>\n \n This multicentre retrospective cohort study included 1198 patients with clinical T3\u20134N0M0 or cN1M0 prostate cancer from the Kaga Million Uro\u2010Oncology Network (KAMU\u2010ON). Multivariable Cox models evaluated the association between local therapy and overall survival. Treatment\u2010effect heterogeneity was assessed using interaction analyses. Adjusted 5 year overall survival and absolute survival benefit were estimated by\n g<\/jats:italic>\n \u2010computation. A simple clinical framework based on clinicopathological variables was derived from the subgroup analyses.\n <\/jats:p>\n <\/jats:sec>\n \n Results<\/jats:title>\n \n Local therapy was independently associated with improved overall survival (adjusted hazard ratio 0.32, 95% confidence interval 0.21\u20130.48;\n p<\/jats:italic>\n \u2009<\u20090.001). Significant treatment\u2010effect heterogeneity was observed according to clinical T stage (\n p<\/jats:italic>\n for interaction\u2009=\u20090.030). The greatest absolute survival benefits were observed in patients with clinical T3b\/T4 disease (20.3 percentage points) and Grade Group 4\u20135 disease (17.2 percentage points). The framework stratified the estimated absolute survival benefit from 0.1 to 19.5 percentage points across score groups (\n p<\/jats:italic>\n for interaction\u2009=\u20090.041;\n p<\/jats:italic>\n for trend\u2009=\u20090.023).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n The survival benefit associated with local therapy varied substantially across patients with nonmetastatic advanced prostate cancer. This hypothesis\u2010generating framework may provide estimates of expected treatment benefit and support individualized treatment discussions.<\/jats:p>\n <\/jats:sec>","DOI":"10.1111\/iju.70668","type":"journal-article","created":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T01:55:46Z","timestamp":1791424546000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Treatment\u2010Effect Heterogeneity and a Simple Framework for Estimating Survival Benefit Associated With Local Therapy in Nonmetastatic Advanced Prostate Cancer: A Multicenter\n KAMU<\/scp>\n \u2010\n ON<\/scp>\n Cohort Study"],"prefix":"10.1111","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3599-2217","authenticated-orcid":false,"given":"Hiroaki","family":"Iwamoto","sequence":"first","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8480-9100","authenticated-orcid":false,"given":"Kouji","family":"Izumi","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuaki","family":"Machioka","sequence":"additional","affiliation":[{"name":"Department of Urology Ishikawa Prefectural Central Hospital Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ren","family":"Toriumi","sequence":"additional","affiliation":[{"name":"Department of Urology Toyama Prefectural Central Hospital Toyama Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Shima","sequence":"additional","affiliation":[{"name":"Department of Urology Toyama Prefectural Central Hospital Toyama Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-3829-6544","authenticated-orcid":false,"given":"Masakazu","family":"Nozaki","sequence":"additional","affiliation":[{"name":"Department of Urology Japanese Red Cross Fukui Hospital Fukui Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-0355-1005","authenticated-orcid":false,"given":"Tomohiro","family":"Hori","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-9449-5421","authenticated-orcid":false,"given":"Takahiro","family":"Inaba","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2503-8908","authenticated-orcid":false,"given":"Ryunosuke","family":"Nakagawa","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-2553-0497","authenticated-orcid":false,"given":"Taiki","family":"Kamijima","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4136-8998","authenticated-orcid":false,"given":"Suguru","family":"Kadomoto","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2554-7048","authenticated-orcid":false,"given":"Tomoyuki","family":"Makino","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3936-7235","authenticated-orcid":false,"given":"Renato","family":"Naito","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3188-8834","authenticated-orcid":false,"given":"Hiroshi","family":"Yaegashi","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2118-9135","authenticated-orcid":false,"given":"Kazuyoshi","family":"Shigehara","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9792-2068","authenticated-orcid":false,"given":"Takahiro","family":"Nohara","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tohru","family":"Miyagi","sequence":"additional","affiliation":[{"name":"Department of Urology Ishikawa Prefectural Central Hospital Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikashi","family":"Seto","sequence":"additional","affiliation":[{"name":"Department of Urology Toyama Prefectural Central Hospital Toyama Toyama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5780-4032","authenticated-orcid":false,"given":"Yoshifumi","family":"Kadono","sequence":"additional","affiliation":[{"name":"Department of Urology Japanese Red Cross Fukui Hospital Fukui Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5643-2182","authenticated-orcid":false,"given":"Atsushi","family":"Mizokami","sequence":"additional","affiliation":[{"name":"Department of Integrative Cancer Therapy and Urology Kanazawa University Graduate School of Medical Science Kanazawa Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,7]]},"reference":[{"key":"e_1_2_12_2_1","first-page":"1","article-title":"Recent Advances in the Management of High\u2010Risk Localized Prostate Cancer: Local Therapy, Systemic Therapy, and Biomarkers to Guide Treatment Decisions","volume":"40","author":"McKay R. 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A.","year":"2021","journal-title":"Translational Andrology and Urology"},{"key":"e_1_2_12_8_1","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1007\/s11864-023-01162-4","article-title":"Surgical Management and Considerations for Patients With Localized High\u2010Risk Prostate Cancer","volume":"25","author":"Fang A. M.","year":"2024","journal-title":"Current Treatment Options in Oncology"},{"key":"e_1_2_12_9_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.eururo.2019.02.003","article-title":"Prostate Radiotherapy for Metastatic Hormone\u2010Sensitive Prostate Cancer: A STOPCAP Systematic Review and Meta\u2010Analysis","volume":"76","author":"Burdett S.","year":"2019","journal-title":"European Urology"},{"key":"e_1_2_12_10_1","doi-asserted-by":"crossref","first-page":"2353","DOI":"10.1016\/S0140-6736(18)32486-3","article-title":"Radiotherapy to the Primary Tumour for Newly Diagnosed, Metastatic Prostate Cancer (STAMPEDE): A Randomised Controlled Phase 3 Trial","volume":"392","author":"Parker C. C.","year":"2018","journal-title":"Lancet"},{"key":"e_1_2_12_11_1","doi-asserted-by":"crossref","first-page":"410","DOI":"10.1016\/j.eururo.2018.09.008","article-title":"Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined With Concurrent Radiation Therapy to the Prostate in Patients With Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data From the HORRAD Trial","volume":"75","author":"Boeve L. M. S.","year":"2019","journal-title":"European Urology"},{"key":"e_1_2_12_12_1","doi-asserted-by":"crossref","DOI":"10.1016\/j.radonc.2023.109746","article-title":"Impact of Prostate Radiotherapy on Survival Outcomes in Clinically Node\u2010Positive Prostate Cancer: A Multicentre Retrospective Analysis","volume":"186","author":"Elumalai T.","year":"2023","journal-title":"Radiotherapy and Oncology"},{"key":"e_1_2_12_13_1","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.euo.2023.09.002","article-title":"Local Therapy on Clinically Lymph Node\u2010Positive Prostate Cancer: A Systematic Review and Meta\u2010Analysis","volume":"7","author":"Yaow C. Y. L.","year":"2024","journal-title":"European Urology Oncology"},{"key":"e_1_2_12_14_1","doi-asserted-by":"crossref","first-page":"35","DOI":"10.7326\/M18-3667","article-title":"The Predictive Approaches to Treatment Effect Heterogeneity (PATH) Statement","volume":"172","author":"Kent D. 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