{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:21:51Z","timestamp":1783686111328,"version":"3.55.0"},"reference-count":17,"publisher":"MDPI AG","issue":"14","license":[{"start":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T00:00:00Z","timestamp":1783641600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Theragenics Corporation"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: High-risk (HR) prostate cancer has a propensity for local and distant progression with ultimate death, mandating aggressive locoregional and systemic treatment approaches to maximize oncologic outcomes. Although brachytherapy (BT) with supplemental therapies has demonstrated favorable biochemical and quality of life outcomes, improvements in overall survival have been hampered by an excessive incidence of non- prostate cancer deaths. In this HR study, we report on biochemical failure (BF), prostate cancer-specific mortality (PCSM), overall mortality (OM) and patterns of death with recommendations for the mitigation of non-prostate cancer deaths. Materials and Methods: From April 1995 to November 2018, 577 consecutive HR patients were treated with LDR BT (97.9% Pd-103). Patients were stratified into three age cohorts: \u2264 59, 60\u201369 and \u226570 years. The BT prescription dose was prescribed to the prostate gland with generous peri-prostatic margins and the proximal 10mm of the seminal vesicles. 94.6% received supplemental EBRT (45\u201350.4 Gy) and 63.3% received androgen deprivation therapy (ADT) (median duration 12 months). Post-implant CT-based dosimetry was performed on day 0. BF was defined as a PSA &gt; 0.40 ng\/mL after nadir. The cause of death was determined for each patient. Patients with metastatic prostate cancer or non-metastatic castrate resistant prostate cancer who died of any cause were classified as dead of prostate cancer. All other deaths were attributed to the immediate cause. Multiple clinical, pathologic and treatment were evaluated for impact on patient outcomes. Results: Of the patients, 87.5% (median follow-up 8.9 years) presented with a single HR factor. The day 0 D90 was 122.5%. Overall, the 15-year BF, PCSM and OM were 12.4%, 5.6% and 51.7%. When stratified by age, there was no significant difference in BF or PCSM. The median post- treatment PSA in biochemically controlled patients was &lt;0.01 ng\/mL. In all three cohorts, OM increased linearly for the first 10 years and then approximately doubled from years 10 to 15. Moreover, 239 patients died: 10.9% due to prostate cancer, 38.1% from cardiovascular (CV) disease and 28.4% from other malignancies (to include one rectal and three bladder cancers). In MVA, BF was most closely related to percent positive biopsies (p &lt; 0.001, SHR 1.018), PCSM to Gleason score (p = 0.004, SHR 2.884) and percent positive biopsies (p = 0.005, SHR 1.021) and OM to age (p &lt; 0.001, HR 1.075) and tobacco (p &lt; 0.001, HR 2.374). Conclusions: Despite high cancer control rates, overall survival was limited by a preponderance of CV and non-prostate cancer deaths, which were 6 times more likely than prostate cancer deaths. The implementation of a comprehensive multidisciplinary survivorship program will be essential to impact longevity in this patient population.<\/jats:p>","DOI":"10.3390\/jcm15145414","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T11:43:34Z","timestamp":1783683814000},"page":"5414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Medical Management of Modifiable Risks: Improving Survival in High-Risk Prostate Cancer Patients Receiving Brachytherapy"],"prefix":"10.3390","volume":"15","author":[{"given":"Shalini","family":"Moningi","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, 9500 Euclide Avenue, CA-50, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grgur","family":"Miri\u0107","sequence":"additional","affiliation":[{"name":"Urologic Research Institute, Sarasota, FL 34236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-4266-2191","authenticated-orcid":false,"given":"Robert W.","family":"Galbreath","sequence":"additional","affiliation":[{"name":"Urologic Research Institute, Sarasota, FL 34236, USA"},{"name":"Department of Exercise Physiology, Ohio University Eastern, St. Clairsville, OH 43950, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1266-7534","authenticated-orcid":false,"given":"Ryan","family":"Fiano","sequence":"additional","affiliation":[{"name":"Urologic Research Institute, Sarasota, FL 34236, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent E.","family":"Wallner","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, University of Washington, Seattle, WA 98195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0101-0951","authenticated-orcid":false,"given":"Mutlay","family":"Sayan","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter F.","family":"Orio","sequence":"additional","affiliation":[{"name":"Dana Farber Cancer Institute, Boston, MA 02215, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"King","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology, Brigham and Women\u2019s Hospital, Boston, MA 02115, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e2456825","DOI":"10.1001\/jamanetworkopen.2024.56825","article-title":"Trends in Prostate Cancer Incidence and Mortality Rates","volume":"8","author":"McKinley","year":"2025","journal-title":"JAMA Netw. Open."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1016\/j.ijrobp.2016.12.014","article-title":"A Comparison Between Low-Dose-Rate Brachytherapy With or Without Androgen Deprivation, External Beam Radiation Therapy With or Without Androgen Deprivation, and Radical Prostatectomy With or Without Adjuvant or Salvage Radiation Therapy for High-Risk Prostate Cancer","volume":"97","author":"Ciezki","year":"2017","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"451","DOI":"10.1016\/S1470-2045(11)70063-8","article-title":"Short-term neoadjuvant androgen deprivation and radiotherapy for locally advanced prostate cancer: 10-year data from the TROG 96.01 randomised trial","volume":"12","author":"Denham","year":"2011","journal-title":"Lancet Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"e276","DOI":"10.1016\/j.prro.2024.10.005","article-title":"Prospective Evaluation of Supplemental External Beam Radiation Therapy with Palladium-103 Prostate Brachytherapy: Long-Term Results of the 44\/20\/0 Trials","volume":"15","author":"King","year":"2025","journal-title":"Pract. Radiat. Oncol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.ijrobp.2016.11.026","article-title":"Androgen Suppression Combined with Elective Nodal and Dose Escalated Radiation Therapy (the ASCENDE-RT Trial): An Analysis of Survival Endpoints for a Randomized Trial Comparing a Low-Dose-Rate Brachytherapy Boost to a Dose-Escalated External Beam Boost for High- and Intermediate-risk Prostate Cancer","volume":"98","author":"Morris","year":"2017","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"896","DOI":"10.1001\/jama.2018.0587","article-title":"Radical Prostatectomy, External Beam Radiotherapy, or External Beam Radiotherapy with Brachytherapy Boost and Disease Progression and Mortality in Patients with Gleason Score 9\u201310 Prostate Cancer","volume":"319","author":"Kishan","year":"2018","journal-title":"JAMA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"122","DOI":"10.1080\/21681805.2017.1421260","article-title":"High Norwegian prostate cancer mortality: Evidence of over-reporting","volume":"52","author":"Halland","year":"2018","journal-title":"Scand. J. Urol."},{"key":"ref_8","first-page":"78","article-title":"Modified uniform seed loading for prostate brachytherapy: Rationale, design and evaluation","volume":"6","author":"Merrick","year":"2006","journal-title":"Tech. Urol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1007\/s00345-018-2389-1","article-title":"Elderly patients aged \u226575 years with locally advanced prostate cancer may benefit from local treatment: A population-based propensity score-adjusted analysis","volume":"37","author":"Sheng","year":"2019","journal-title":"World J. Urol."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Moningi, S., Miri\u0107, G., Galbreath, R., Fiano, R., Wallner, K., Sayan, M., Orio, P., and King, M. (2025). Long-term prostate cancer survival outcomes including patterns of death in men >=75 years of age treated with low dose rate brachytherapy. BMC Geriatr., 26.","DOI":"10.1186\/s12877-025-06883-9"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1097\/JU.0000000000000714","article-title":"Cardiovascular Risk in Men with Prostate Cancer: Insights from the RADICAL PC Study","volume":"203","author":"Leong","year":"2020","journal-title":"J. Urol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1001\/jamaoncol.2024.1549","article-title":"Cardiovascular Events and Androgen Receptor Signaling Inhibitors in Advanced Prostate Cancer: A Systematic Review and Meta-Analysis","volume":"10","author":"Taktak","year":"2024","journal-title":"JAMA Oncol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e210070","DOI":"10.1001\/jamanetworkopen.2021.0070","article-title":"Assessment and Management of Cardiovascular Risk Factors Among US Veterans with Prostate Cancer","volume":"4","author":"Sun","year":"2021","journal-title":"JAMA Netw. Open."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1016\/j.euo.2023.11.024","article-title":"Testosterone Recovery for Relugolix Versus Leuprolide in Men with Advanced Prostate Cancer: Results from the Phase 3 HERO Study","volume":"7","author":"Tutrone","year":"2024","journal-title":"Eur. Urol. Oncol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"523","DOI":"10.1161\/CIRCULATIONAHA.121.058162","article-title":"Long-Term Leisure-Time Physical Activity Intensity and All-Cause and Cause-Specific Mortality: A Prospective Cohort of US Adults","volume":"146","author":"Lee","year":"2022","journal-title":"Circulation"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15","DOI":"10.5334\/gh.1399","article-title":"Cardiovascular Effects of Smoking and Smoking Cessation: A 2024 Update","volume":"20","author":"Rahman","year":"2025","journal-title":"Glob. Heart"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1016\/j.ijrobp.2025.06.3900","article-title":"Beyond the Beam: Redefining Survivorship in Prostate Cancer","volume":"123","author":"Sayan","year":"2025","journal-title":"Int. J. Radiat. Oncol. Biol. Phys."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5414\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T12:08:01Z","timestamp":1783685281000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/15\/14\/5414"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,10]]},"references-count":17,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["jcm15145414"],"URL":"https:\/\/doi.org\/10.3390\/jcm15145414","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,10]]}}}