{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T11:28:37Z","timestamp":1787138917079,"version":"build-2736575974"},"reference-count":50,"publisher":"Wiley","issue":"16","license":[{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T00:00:00Z","timestamp":1786492800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>\n                      Disease\u2010free survival (DFS) is commonly used as a primary end point in trials for localized renal cell carcinoma (\n                      <jats:italic>R<\/jats:italic>\n                      CC), although its validity as a surrogate for overall survival (OS) remains uncertain. The objective of this study was to evaluate whether DFS is a reliable surrogate end point for OS in this setting.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The authors conducted a systematic review and trial\u2010level meta\u2010analysis of randomized controlled trials assessing systemic or perioperative therapies in patients with localized RCC. Databases were searched from inception to June 10, 2025. Trial\u2010level surrogacy between DFS and OS was assessed using weighted least\u2010squares meta\u2010regression of log\u2010transformed hazard ratios (HRs), and the surrogate threshold effect was estimated.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>In total, 25 randomized controlled trials were analyzed; 13 trials, analyzed as 15 study\u2010level units comprising 9594 patients, reported HRs for both OS and DFS. DFS demonstrated a strong correlation with OS (weighted Pearson correlation coefficient, 0.75; 95% confidence level, 0.55\u20130.91; corresponding coefficient of determination, 0.57). The surrogate threshold effect analysis identified a DFS HR &lt;0.914 as predictive of OS benefit. Funnel plots showed no clear asymmetry, and Egger tests did not indicate significant publication bias.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>DFS demonstrated a strong association with OS and may serve as a valid trial\u2010level surrogate end point patients with in localized RCC. A DFS HR &lt;0.914 was more likely to predict an OS benefit. These findings support the use of DFS as a primary end point in localized RCC trials, whereas continued long\u2010term follow\u2010up and future patient\u2010level validation remain important.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.70567","type":"journal-article","created":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T06:59:31Z","timestamp":1786604371000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Disease\u2010free survival as a surrogate outcome for localized kidney cancer\u2014A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"132","author":[{"given":"Constanza","family":"Martinez","sequence":"first","affiliation":[{"name":"Department of Radiation Oncology McGill University Health Center  Montreal Quebec Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chen","sequence":"additional","affiliation":[{"name":"Radiation 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