{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T18:00:30Z","timestamp":1791223230232,"version":"4.1.0"},"reference-count":76,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"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":[[2026,10,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The objective of this systematic review and meta\u2010analysis was to evaluate the validity of progression\u2010free survival (PFS) and the objective response rate (ORR) as surrogate end points for overall survival (OS) in randomized controlled trials (RCTs) of metastatic renal cell carcinoma. The MEDLINE, Embase, and Cochrane CENTRAL databases were searched from inception to June 10, 2025. Associations between treatment effects on OS, PFS, and ORR were assessed using Pearson correlation coefficients (\n                    <jats:italic>r<\/jats:italic>\n                    ). Surrogate threshold effect (STE) analyses determined the minimum PFS hazard ratio (HR) or ORR odds ratio (OR) required to predict OS benefit. Subgroup analyses were conducted by treatment class, line of therapy, and histology. Sixty\u2010two randomized controlled trials comprising 24,518 patients were included. PFS\u2010OS demonstrated a moderate correlation (\n                    <jats:italic>r<\/jats:italic>\n                    \u00a0=\u00a00.52; 95% confidence interval [CI], 0.38\u20130.66), with an STE (HR, 0.92; 95% CI, 0.79\u20131.09). ORR\u2010OS demonstrated a moderate correlation (\n                    <jats:italic>r<\/jats:italic>\n                    \u00a0=\u00a0\u22120.59; 95% CI, \u22120.72, \u22120.45), with an STE (OR, 1.40; 95% CI, 0.99\u20131.89). Subgroup estimates varied across treatment settings and were frequently imprecise, particularly for ORR and in smaller treatment\u2010class subgroups; limited representation of non\u2013clear cell renal cell carcinoma precluded reliable histology\u2010specific conclusions. Overall, PFS and ORR had moderate trial\u2010level associations with OS in metastatic renal cell carcinoma, but the overall analyses did not demonstrate sufficiently consistent surrogacy to reliably predict OS benefit. These findings should be interpreted cautiously given the substantial heterogeneity of the included trials. Surrogate validity appears to be context\u2010dependent, supporting continued reliance on OS and the need for more robust surrogate end points.\n                  <\/jats:p>","DOI":"10.1002\/cncr.70616","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T07:29:47Z","timestamp":1790234987000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Progression\u2010free survival and objective response rate as a surrogate end point for overall survival in metastatic renal cell carcinoma: A systematic review and meta\u2010analysis"],"prefix":"10.1002","volume":"132","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5030-7487","authenticated-orcid":false,"given":"Russell","family":"Leong","sequence":"first","affiliation":[{"name":"Faculty of Medicine University of Ottawa  Ottawa Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology BC Cancer Vancouver  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laith","family":"Almasri","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas","family":"Lum","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karren","family":"Xiao","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maryam","family":"Soleimani","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology BC Cancer Vancouver  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian K.","family":"Kollmannsberger","sequence":"additional","affiliation":[{"name":"Department of Medical Oncology BC Cancer Vancouver  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Srinivas","family":"Raman","sequence":"additional","affiliation":[{"name":"Department of Radiation Oncology BC Cancer Vancouver  Vancouver British Columbia Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1200\/OP.21.00419"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1503\/cmaj.230356"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eururo.2022.03.006"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1097\/PPO.0b013e3181b9c602"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201024\u20101199"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1991.9.12.2104"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(98)03544-2"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/s0140\u20106736(01)06103\u20107"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.07.114"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6602768"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2005.03.206"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.11.5154"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa060655"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa066838"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.23056"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(08)61039\u20109"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2007.14.5029"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2008.20.1293"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201010\u20102082"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.26.7849"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(09)61921\u20108"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.24685"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(13)70093\u20107"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1303989"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.50.3961"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(14)70030\u20100"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2013.54.6911"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1510665"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdv170"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(15)00515\u2010X"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(16)30107\u20103"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11523\u2010016\u20100434\u20109"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8808"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(16)30408\u20109"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2016.5202"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx493"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2018.02.012"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1803675"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2018.5543"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140\u20106736(19)30723\u20108"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.32061"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1159\/000508450"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.2218"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201019\u20102427"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(20)30436\u20108"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470\u20102045(19)30735\u20101"},{"key":"e_1_2_9_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.euo.2019.06.004"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clgc.2020.01.001"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010021\u201026415\u20104"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/onco.13628"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.1093\/oncolo\/oyac192"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1159\/000522043"},{"key":"e_1_2_9_54_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078\u20100432.CCR\u201022\u20100061"},{"key":"e_1_2_9_55_1","do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