{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T03:08:32Z","timestamp":1784862512025,"version":"3.55.0"},"reference-count":59,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T00:00:00Z","timestamp":1743638400000},"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><jats:title>Background<\/jats:title><jats:p>Cryotherapy plays a crucial role in managing radio-recurrent prostate cancer (PCa) after initial treatment. This study aims to provide a comprehensive review of its effectiveness and associated complications.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A systematic review was conducted using PubMed and EMBASE databases up to June 2024, focusing on recurrence-free survival (RFS) with salvage cryotherapy across various subgroups. Severe complications were also assessed. Survival curves were reconstructed using WebPlotDigitizer and a newly developed Shiny application. The incidence of complications was summarized with a 95% confidence interval (CI) using a random-effects model. Complications were evaluated using the Clavien-Dindo Scale (CDS).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Thirty-six studies were included, with 15 papers (3174 patients) contributing to survival curve reconstruction. Among 1593 patients treated with salvage cryotherapy, the median RFS was 56.7 months, with 2-, 3-, and 5-year rates of 67.6%, 59.5%, and 47.3%, respectively. Factors associated with better RFS included a longer time from primary treatment to salvage therapy (TRS) [&amp;gt; 70 months vs. &amp;lt; 70 months, hazard ratio (HR) (95% CI):0.75(0.58-0.97), p=0.031], lower pre-salvage prostate-specific antigen (PSA) levels [&amp;lt; 5 ng\/mL vs. &amp;gt; 5 ng\/mL, HR (95% CI):0.78 (0.65-0.93), p=0.005], salvage whole-gland cryotherapy (SWC) [whole vs. focal, HR (95% CI):0.45 (0.37-0.56), p &amp;lt; 0.001], neoadjuvant androgen deprivation therapy (ADT) [Yes vs. No, HR (95% CI):0.79 (0.69-0.89), p &amp;lt; 0.001], and higher adjuvant ADT usage [16.5-34.2% vs. 0-10.5%, HR (95% CI):0.47(0.39-0.56), p &amp;lt; 0.001]. Concerning severe complications, 78 out of 876 patients (8.9%, 95% CI: 7-11) experienced genitourinary (GU) events, 53 out of 633 patients (8.5%, 95% CI: 6-11) suffered from urinary incontinence, 15 out of 493 patients (3.0%, 95% CI: 2-5) had urethral sloughing\/stenosis, and 6 out of 522 patients (1.1%, 95% CI: 0-2) developed recto-urethral\/vesical fistula. No cases of severe haematuria, urinary tract infection, or urinary retention were reported.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Cryotherapy demonstrates a favorable safety profile and significant RFS benefits for salvage treatment of radio-recurrent PCa. Longer TRS, lower pre-salvage PSA, SWC, and peri-salvage ADT usage appear to be promising prognostic factors for RFS. However, confirmation of these findings requires randomized controlled trials (RCTs) due to the low evidence levels and study heterogeneity.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fonc.2025.1534739","type":"journal-article","created":{"date-parts":[[2025,4,3]],"date-time":"2025-04-03T04:11:40Z","timestamp":1743653500000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Oncological effects and complications of salvage cryotherapy for radio-recurrent prostate cancer: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Shengyu","family":"Zhu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianjiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huali","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Jin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,4,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.adro.2019.01.004","article-title":"Regional differences in the treatment of localized prostate cancer: an analysis of surgery and radiation utilization in the United States","volume":"4","author":"Scherzer","year":"2019","journal-title":"Adv Radiat Oncol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2018.19941","article-title":"Use of active surveillance or watchful waiting for low-risk prostate cancer and management trends across risk groups in the United States, 2010-2015","volume":"321","author":"Mahal","year":"2019","journal-title":"JAMA"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1159\/000339616","article-title":"High-intensity focused ultrasound and cryotherapy as salvage treatment in local radio-recurrent prostate cancer","volume":"89","author":"Autran-Gomez","year":"2012","journal-title":"Urol Int"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1007\/s00345-016-1811-9","article-title":"Focal salvage therapy for local prostate cancer recurrences after primary radiotherapy: a comprehensive review","volume":"34","author":"Duijzentkunst","year":"2016","journal-title":"World J Urol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1007\/s11934-017-0709-4","article-title":"Salvage therapy options for local prostate cancer recurrence after primary radiotherapy: a literature review","volume":"18","author":"Golbari","year":"2017","journal-title":"Curr Urol Rep"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2020.09.042","article-title":"EAU-EANM-ESTRO-ESUR-SIOG guidelines on prostate cancer-2020 update. 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