{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T02:01:35Z","timestamp":1793152895559,"version":"4.5.0"},"reference-count":29,"publisher":"American Society of Clinical Oncology (ASCO)","issue":"34","content-domain":{"domain":["ascopubs.org"],"crossmark-restriction":true},"short-container-title":["J Clin Oncol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:sec>\n                    <jats:title>PURPOSE<\/jats:title>\n                    <jats:p>Active surveillance (AS) is a standard management strategy for low-risk prostate cancer (PCa), but a significant proportion of patients ultimately experience disease progression. Metformin, a commonly prescribed antidiabetic agent, has demonstrated antitumor activity in preclinical studies and observational data, prompting investigation into its potential to delay PCa progression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>PATIENTS AND METHODS<\/jats:title>\n                    <jats:p>The Metformin Active Surveillance Trial (MAST) was a multicenter, randomized, double-blind, placebo-controlled phase III trial evaluating the efficacy of metformin in men with low-risk, localized PCa managed with AS. Eligible participants were randomly assigned 1:1 to receive either metformin (850 mg twice daily) or placebo and were followed for up to 36 months. The primary end point was time to progression, defined as therapeutic and\/or pathologic progression. Progression-free survival (PFS) was assessed using Kaplan-Meier analysis and Cox proportional hazards models.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>\n                      A total of 408 patients were randomly assigned (205 metformin, 203 placebo). After a median follow-up of 36 months, 144 participants experienced progression (70 metformin, 74 placebo), with no significant difference in PFS (hazard ratio [HR], 1.09 [95% CI, 0.79 to 1.52];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .59). Negative biopsy rates at 36 months were 41.0% (metformin) versus 31.1% (placebo;\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .181). In prespecified subgroup analysis, metformin was associated with increased pathologic progression among obese patients (BMI \u2265 30; HR, 2.36 [95% CI, 1.21 to 4.59];\n                      <jats:italic toggle=\"yes\">P<\/jats:italic>\n                      = .0092).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSION<\/jats:title>\n                    <jats:p>Metformin did not reduce progression in men with low-risk PCa on AS. The observed adverse effect in obese patients merits further investigation.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1200\/jco-25-01070","type":"journal-article","created":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T20:00:13Z","timestamp":1761854413000},"page":"3662-3671","update-policy":"https:\/\/doi.org\/10.1200\/crossmark","source":"Crossref","is-referenced-by-count":13,"title":["Metformin Active Surveillance Trial in Low-Risk Prostate Cancer"],"prefix":"10.1200","volume":"43","clinical-trial-number":[{"clinical-trial-number":"nct01864096","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7407-7463","authenticated-orcid":true,"given":"Neil E.","family":"Fleshner","sequence":"first","affiliation":[{"name":"Division of Urologic Oncology, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, 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