{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T00:32:09Z","timestamp":1791765129739,"version":"4.3.4"},"reference-count":41,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Brief overview of high-risk\/locally advanced prostate cancer in older adults, current neoadjuvant therapies (NHT, NNHT, NCHT), and the uncertainty regarding their comparative efficacy on pathological outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aims to compare the efficacy and safety profiles of various neoadjuvant treatments in improving pathological outcomes\u2014including positive surgical margin (PSM) rates, minimal residual disease (MRD), clinical downstaging, and post-treatment prostate-specific antigen (PSA) reduction\u2014in older adults with high-risk or locally advanced prostate cancer.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched PubMed, Embase, the Cochrane Library, and Web of Science for relevant randomized controlled trials and prospective comparative studies published from January 2010 to April 20, 2025. The primary pathological outcomes were positive surgical margin (PSM) rate and minimal residual disease (MRD). Secondary outcomes included clinical downstaging and prostate-specific antigen (PSA) response. All network meta-analyses were performed using Bayesian frameworks, with treatment ranking evaluated via the surface under the cumulative ranking curve (SUCRA).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The network meta-analysis of 15 studies revealed that, according to surface under the cumulative ranking curve (SUCRA) values, novel neoadjuvant hormonal therapy (NNHT) ranked highest for improving key pathological outcomes\u2014notably surgical margin status and post-treatment prostate-specific antigen (PSA) response. While NNHT achieved the highest pathological response rates, it was associated with the most frequent and severe adverse events, highlighting a critical efficacy-toxicity trade-off in clinical decision-making.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Our analysis identifies NNHT as the most effective neoadjuvant approach for optimizing pathological endpoints, despite its association with the highest toxicity burden. This efficacy-safety profile supports its prioritization in subsequent trials designed to evaluate long-term survival and comprehensively assess safety outcomes in this population.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/prospero\/<\/jats:ext-link>\n                      , identifier CRD420251233339.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1796138","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T04:40:22Z","timestamp":1779338422000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Efficacy and safety of neoadjuvant therapies for high-risk and locally advanced prostate cancer in older adults: a systematic review and network meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Wenling","family":"Yuan","sequence":"first","affiliation":[{"name":"Department of Pharmacy, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangyuan","family":"Tian","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengran","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, West China Hospital, Sichuan University","place":["Chengdu, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"12","DOI":"10.3322\/caac.21820","article-title":"Cancer statistics, 2024","volume":"74","author":"Siegel","year":"2024","journal-title":"Ca-A Cancer J For Clin"},{"key":"B2","doi-asserted-by":"publisher","first-page":"191","DOI":"10.5215\/pennmaghistbio.136.2.0220","article-title":"2022 update on prostate cancer epidemiology and risk factors-a systematic review","volume":"84","author":"Bergengren","year":"2023","journal-title":"Eur Urol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a030361","article-title":"The epidemiology of prostate cancer","volume":"8","author":"Pernar","year":"2018","journal-title":"Cold Spring Harbor Perspect Med"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.08.1508","article-title":"Impact of geriatric assessment on therapeutic decision in elderly patients with cancer","volume":"209","author":"Miraoui","year":"2025","journal-title":"Bull L Academie Nationale Medecine"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.3390\/cancers17010099","article-title":"Current status of neoadjuvant treatment before surgery in high-risk localized prostate cancer","volume":"17","author":"Rivas","year":"2025","journal-title":"Cancers"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/0022-4731(83)90046-8","article-title":"New hormonal-therapy in prostatic-carcinoma - 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