{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T19:07:26Z","timestamp":1784228846972,"version":"3.55.0"},"reference-count":31,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T00:00:00Z","timestamp":1784160000000},"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":["The Prostate"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The Phoenix definition is widely used to define biochemical recurrence (BCR) after radiation therapy for prostate cancer; however, a definitive definition of cure remains unclear. This study aimed to identify factors associated with late BCR after low\u2010dose\u2010rate brachytherapy (LDR\u2010BT), defined as BCR occurring \u2265\u20095 years after treatment among patients who remained recurrence\u2010free during the first 5 years, using machine\u2010learning methods.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We retrospectively analyzed 1419 patients who underwent LDR\u2010BT between 2004 and 2019. Of these, 52 (3.7%) experienced BCR within 5 years, and 244 patients did not have \u2265\u20095 years of follow\u2010up because of death or loss to follow\u2010up. The remaining 1123 patients were recurrence\u2010free at 5 years and formed the analysis cohort for late BCR (\u2265\u20095 years). Random survival forest (RSF) and survival decision\u2010tree analyses were applied to identify predictive factors, and recurrence\u2010free survival was estimated using the Kaplan\u2013Meier method.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The 10\u2010year BCR\u2010free survival rate was 94.8%. RSF identified the 5\u2010year prostate\u2010specific antigen (PSA) value, PSA doubling time (PSA\u2010DT) at 5 years, primary Gleason pattern, and NCCN risk classification as the most important predictors. Optimal cutoff values were 0.93\u2009ng\/mL for PSA at 5 years and 5.3 years for PSA\u2010DT. Patients with lower PSA or longer PSA\u2010DT had significantly higher 10\u2010year recurrence\u2010free rates than those at higher risk (97.3% vs. 11.1% and 99.0% vs. 68.1%, respectively;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PSA level and PSA\u2010DT at 5 years were strong predictors of late BCR after LDR\u2010BT. These findings suggest that follow\u2010up intervals may be safely extended for low\u2010risk patients, thereby reducing the burden of hospital visits and healthcare costs.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/pros.70219","type":"journal-article","created":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:39:04Z","timestamp":1784227144000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluating Risk Factors Associating With Late Recurrence After Low\u2010Dose\u2010Rate Brachytherapy for Prostate Cancer Using Machine Learning"],"prefix":"10.1002","author":[{"given":"Kenta","family":"Onishi","sequence":"first","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomonori","family":"Nakahama","sequence":"additional","affiliation":[{"name":"Department of Urology Hirao Hospital Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7579-0372","authenticated-orcid":false,"given":"Yasushi","family":"Nakai","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akira","family":"Tachibana","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Oda","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mitsuru","family":"Tomizawa","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7142-5901","authenticated-orcid":false,"given":"Yosuke","family":"Morizawa","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunta","family":"Hori","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6056-3820","authenticated-orcid":false,"given":"Daisuke","family":"Gotoh","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9503-7356","authenticated-orcid":false,"given":"Makito","family":"Miyake","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isao","family":"Asakawa","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Nara City Hospital Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Yamaki","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fumiaki","family":"Isohashi","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyohide","family":"Fujimoto","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9242-7877","authenticated-orcid":false,"given":"Nobumichi","family":"Tanaka","sequence":"additional","affiliation":[{"name":"Department of Urology Nara Medical University Nara Japan"},{"name":"Department of Prostate Brachytherapy Nara Medical University Nara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,16]]},"reference":[{"issue":"6","key":"e_1_2_11_2_1","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/j.eururo.2023.09.024","article-title":"Long\u2010Term Prostate Cancer\u2010Specific Mortality After Prostatectomy, Brachytherapy, External Beam Radiation Therapy, Hormonal Therapy, or Monitoring for Localized Prostate Cancer","volume":"85","author":"Herlemann A.","year":"2024","journal-title":"European Urology"},{"issue":"5","key":"e_1_2_11_3_1","doi-asserted-by":"crossref","first-page":"1061","DOI":"10.1016\/j.ijrobp.2022.11.005","article-title":"An Updated Analysis of the Survival Endpoints of ASCENDE\u2010RT","volume":"115","author":"Oh J.","year":"2023","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"4","key":"e_1_2_11_4_1","doi-asserted-by":"crossref","first-page":"965","DOI":"10.1016\/j.ijrobp.2006.04.029","article-title":"Defining Biochemical Failure Following Radiotherapy With or Without Hormonal Therapy in Men With Clinically Localized Prostate Cancer: Recommendations of the RTOG\u2013ASTRO Phoenix Consensus Conference","volume":"65","author":"Roach M.","year":"2006","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"1","key":"e_1_2_11_5_1","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1007\/s10147-021-02040-5","article-title":"How Long Is Long Enough to Secure Disease Control After Low\u2010Dose\u2010Rate Brachytherapy in Combination With Other Modalities in Intermediate\u2010Risk, Localized Prostate Cancer?","volume":"27","author":"Urabe F.","year":"2022","journal-title":"International Journal of Clinical Oncology"},{"key":"e_1_2_11_6_1","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.radonc.2020.04.038","article-title":"A Biochemical Definition of Cure After Brachytherapy for Prostate Cancer","volume":"149","author":"Crook J. M.","year":"2020","journal-title":"Radiotherapy and Oncology"},{"issue":"1","key":"e_1_2_11_7_1","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.clon.2021.11.009","article-title":"Defining Biochemical Cure After Low Dose Rate Prostate Brachytherapy: External Validation of 4\u2010Year Prostate\u2010Specific Antigen Nadir as a Predictor of 10\u2010 and 15\u2010Year Disease\u2010Free Survival","volume":"34","author":"Noble D. J.","year":"2022","journal-title":"Clinical Oncology"},{"issue":"1","key":"e_1_2_11_8_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1016\/j.ijrobp.2013.10.010","article-title":"Prostate\u2010Specific Antigen at 4 to 5 Years After Low\u2010Dose\u2010Rate Prostate Brachytherapy Is a Strong Predictor of Disease\u2010Free Survival","volume":"88","author":"Lo A. C.","year":"2014","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"1","key":"e_1_2_11_9_1","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1016\/j.brachy.2020.07.006","article-title":"Time to Achieve a Prostate\u2010Specific Antigen Nadir of \u22640.2 ng\/mL and Related Factors After Permanent Prostate Brachytherapy","volume":"20","author":"Soyano T.","year":"2021","journal-title":"Brachytherapy"},{"issue":"6","key":"e_1_2_11_10_1","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1016\/j.brachy.2018.08.018","article-title":"Selection of Patients Who Would Not Require Long\u2010Term Prostate\u2010Specific Antigen Monitoring After Low\u2010Dose\u2010Rate Brachytherapy","volume":"17","author":"Niwa N.","year":"2018","journal-title":"Brachytherapy"},{"issue":"2","key":"e_1_2_11_11_1","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/j.ijrobp.2011.07.009","article-title":"PSA Nadir of <0.5 ng\/mL Following Brachytherapy for Early\u2010Stage Prostate Adenocarcinoma Is Associated With Freedom From Prostate\u2010Specific Antigen Failure","volume":"83","author":"Ko E. C.","year":"2012","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"5","key":"e_1_2_11_12_1","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1111\/bju.14122","article-title":"Low\u2010Dose\u2010Rate Brachytherapy for Prostate Cancer: Outcomes at >10 Years of Follow\u2010Up","volume":"121","author":"Lazarev S.","year":"2018","journal-title":"BJU International"},{"issue":"27","key":"e_1_2_11_13_1","doi-asserted-by":"crossref","first-page":"3172","DOI":"10.1200\/JCO.21.02741","article-title":"Biochemical Failure Is Not a Surrogate End Point for Overall Survival in Recurrent Prostate Cancer: Analysis of NRG Oncology\/RTOG 9601","volume":"40","author":"Jackson W. C.","year":"2022","journal-title":"Journal of Clinical Oncology"},{"issue":"32","key":"e_1_2_11_14_1","doi-asserted-by":"crossref","first-page":"5005","DOI":"10.1200\/JCO.23.00617","article-title":"Biochemical Recurrence Surrogacy for Clinical Outcomes After Radiotherapy for Adenocarcinoma of the Prostate","volume":"41","author":"Roy S.","year":"2023","journal-title":"Journal of Clinical Oncology"},{"issue":"3","key":"e_1_2_11_15_1","doi-asserted-by":"crossref","first-page":"213","DOI":"10.1200\/JCO.18.00154","article-title":"Time Interval to Biochemical Failure as a Surrogate End Point in Locally Advanced Prostate Cancer: Analysis of Randomized Trial NRG\/RTOG 9202","volume":"37","author":"Dignam J. J.","year":"2019","journal-title":"Journal of Clinical Oncology"},{"issue":"2","key":"e_1_2_11_16_1","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1038\/s41391-023-00712-z","article-title":"Biochemical Recurrence in Patients With Prostate Cancer After Primary Definitive Therapy: Treatment Based on Risk Stratification","volume":"27","author":"Shore N. D.","year":"2024","journal-title":"Prostate Cancer and Prostatic Diseases"},{"issue":"1","key":"e_1_2_11_17_1","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1111\/bju.13946","article-title":"Long\u2010Term Oncological Outcomes and Toxicity in 597 Men Aged \u226460 Years at Time of Low\u2010Dose\u2010Rate Brachytherapy for Localised Prostate Cancer","volume":"121","author":"Langley S. E. M.","year":"2018","journal-title":"BJU International"},{"issue":"6","key":"e_1_2_11_18_1","doi-asserted-by":"crossref","first-page":"1148","DOI":"10.1007\/s10147-018-1309-0","article-title":"Nationwide Japanese Prostate Cancer Outcome Study of Permanent Iodine\u2010125 Seed Implantation (J\u2010POPS): First Analysis on Survival","volume":"23","author":"Ito K.","year":"2018","journal-title":"International Journal of Clinical Oncology"},{"issue":"2","key":"e_1_2_11_19_1","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1016\/j.ijrobp.2011.07.033","article-title":"Predictors of Metastatic Disease After Prostate Brachytherapy","volume":"83","author":"Forsythe K.","year":"2012","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"2","key":"e_1_2_11_20_1","doi-asserted-by":"crossref","first-page":"e225","DOI":"10.1016\/j.ijrobp.2011.04.046","article-title":"Distant Metastases Following Permanent Interstitial Brachytherapy for Patients With Clinically Localized Prostate Cancer","volume":"82","author":"Taira A. V.","year":"2012","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"12","key":"e_1_2_11_21_1","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1111\/iju.15051","article-title":"Local Dose (Biologically Effective Dose \u2265180\u2009Gy2) Is an Important Predictor of Biochemical Recurrence in Patients Undergoing Low\u2010Dose\u2010Rate Brachytherapy","volume":"29","author":"Tanaka N.","year":"2022","journal-title":"International Journal of Urology"},{"issue":"1","key":"e_1_2_11_22_1","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.ijrobp.2007.05.047","article-title":"Interval to Biochemical Failure Highly Prognostic for Distant Metastasis and Prostate Cancer\u2010Specific Mortality After Radiotherapy","volume":"70","author":"Buyyounouski M. K.","year":"2008","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"key":"e_1_2_11_23_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1471-2490-12-28","article-title":"Minimal Percentage of Dose Received by 90% of the Urethra (%UD90) Is the Most Significant Predictor of PSA Bounce in Patients Who Underwent Low\u2010Dose\u2010Rate Brachytherapy (LDR\u2010Brachytherapy) for Prostate Cancer","volume":"12","author":"Tanaka N.","year":"2012","journal-title":"BMC Urology"},{"issue":"6","key":"e_1_2_11_24_1","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1016\/j.brachy.2024.09.003","article-title":"Prostate\u2010Specific Antigen (PSA) Nadir and Experience of PSA Bounce After Low\u2010Dose\u2010Rate Brachytherapy for Prostate Cancer Predicts Clinical Failure","volume":"23","author":"Nakai Y.","year":"2024","journal-title":"Brachytherapy"},{"key":"e_1_2_11_25_1","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1186\/1748-717X-8-170","article-title":"A Prostate\u2010Specific Antigen Doubling Time of <6 Months Is Prognostic for Metastasis and Prostate Cancer\u2010Specific Death for Patients Receiving Salvage Radiation Therapy Post Radical Prostatectomy","volume":"8","author":"Jackson W. C.","year":"2013","journal-title":"Radiation Oncology (London, England)"},{"issue":"5","key":"e_1_2_11_26_1","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.ijrobp.2008.02.069","article-title":"In Patients Experiencing Biochemical Failure After Radiotherapy, Pretreatment Risk Group and PSA Velocity Predict Differences in Overall Survival and Biochemical Failure\u2010Free Interval","volume":"71","author":"Soto D. E.","year":"2008","journal-title":"International Journal of Radiation Oncology, Biology, Physics"},{"issue":"5","key":"e_1_2_11_27_1","first-page":"1807","article-title":"Risk Factors for Early Arteriovenous Fistula Failure in Patients Undergoing Hemodialysis and Comparison of Diagnostic Prediction Models","volume":"82","author":"Hori S.","year":"2025","journal-title":"Journal of Vascular Surgery"},{"issue":"1","key":"e_1_2_11_28_1","doi-asserted-by":"crossref","first-page":"1446","DOI":"10.1186\/s12885-024-13203-8","article-title":"Time\u2010Dependent Personalized Prognostic Analysis by Machine Learning in Biochemical Recurrence After Radical Prostatectomy: A Retrospective Cohort Study","volume":"24","author":"Sato K.","year":"2024","journal-title":"BMC Cancer"},{"issue":"19","key":"e_1_2_11_29_1","doi-asserted-by":"crossref","first-page":"7079","DOI":"10.3390\/jcm14197079","article-title":"Predicting Biochemical Recurrence After Robot\u2010Assisted Prostatectomy With Interpretable Machine Learning Model","volume":"14","author":"Zhang T.","year":"2025","journal-title":"Journal of Clinical Medicine"},{"key":"e_1_2_11_30_1","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.phro.2018.06.005","article-title":"Biochemical Recurrence Prediction After Radiotherapy for Prostate Cancer With T2w Magnetic Resonance Imaging Radiomic Features","volume":"7","author":"Dinis Fernandes C.","year":"2018","journal-title":"Physics and Imaging in Radiation Oncology"},{"key":"e_1_2_11_31_1","doi-asserted-by":"crossref","first-page":"731","DOI":"10.3389\/fonc.2020.00731","article-title":"Radiomics of Multiparametric MRI to Predict Biochemical Recurrence of Localized Prostate Cancer After Radiation Therapy","volume":"10","author":"Zhong Q. Z.","year":"2020","journal-title":"Frontiers in Oncology"},{"key":"e_1_2_11_32_1","doi-asserted-by":"crossref","DOI":"10.2196\/60323","article-title":"A Machine Learning Approach for Predicting Biochemical Outcome After PSMA\u2010PET\u2010Guided Salvage Radiotherapy in Recurrent Prostate Cancer After Radical Prostatectomy: Retrospective Study","volume":"10","author":"Janbain A.","year":"2024","journal-title":"JMIR Cancer"}],"container-title":["The Prostate"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70219","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/pros.70219","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/pros.70219","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T18:39:08Z","timestamp":1784227148000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/pros.70219"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,16]]},"references-count":31,"alternative-id":["10.1002\/pros.70219"],"URL":"https:\/\/doi.org\/10.1002\/pros.70219","archive":["Portico"],"relation":{},"ISSN":["0270-4137","1097-0045"],"issn-type":[{"value":"0270-4137","type":"print"},{"value":"1097-0045","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,16]]},"assertion":[{"value":"2026-01-07","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"pros.70219"}}