{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T00:06:30Z","timestamp":1760486790266,"version":"build-2065373602"},"reference-count":41,"publisher":"Oxford University Press (OUP)","issue":"10","license":[{"start":{"date-parts":[[2025,9,18]],"date-time":"2025-09-18T00:00:00Z","timestamp":1758153600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Joseph and Silvana Melara Cancer Fund, Toronto\/ON, Canada"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>The weighted toxicity score (WTS) is a metric suitable for comparing the toxicity burden in experimental versus control arms of randomized controlled trials (RCTs). When paired with clinical endpoints, the WTS offers a framework to evaluate the toxicity-benefit profile of anti-cancer agents. This study applied the WTS to phase III advanced prostate cancer (PC) clinical trials.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Design<\/jats:title>\n                  <jats:p>Select phase III PC RCTs with adverse event (AE) data were compiled. The WTS was calculated for each trial arm using 2 approaches: (1) all AEs (A-WTS) and (2) symptomatic AEs (S-WTS). Percent change in WTS between trial arms quantified the toxicity burden, while hazard ratios (HRs) for overall survival (OS) and progression-free survival (PFS) were used to assess efficacy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Seventeen RCTs were analyzed (investigational agents: androgen-receptor signaling inhibitors [ARSi, n\u2009=\u20094], poly (ADP-ribose) polymerase inhibitor monotherapy [PARPi, n\u2009=\u20092], ARSi\u2009+\u2009PARPi [n\u2009=\u20093], ARSi\u2009+\u2009ARSi [n\u2009=\u20093], triplet therapy [n\u2009=\u20093], and docetaxel as well as Lutetium-177 (177Lu)\u2013PSMA-617) [n\u2009=\u20091 each]). Overall, toxicity and efficacy were greater among experimental than control arms (median A-WTS 6.62 vs. 4.10; median S-WTS 3.91 vs. 3.08; median HR for OS 0.75, median HR for PFS 0.61). ARSi\u2009+\u2009PARPi studies observed the highest average A-WTS increase (78%), whereas ARSi\u2009+\u2009ARSi and triplet therapy trials noted the lowest average A-WTS increases (31% and 32%, respectively) with favorable clinical outcomes.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions and Relevance<\/jats:title>\n                  <jats:p>RCTs demonstrated increased toxicity in experimental arms relative to controls, with both toxicity and survival outcomes varying across therapeutic strategies.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/oncolo\/oyaf279","type":"journal-article","created":{"date-parts":[[2025,9,20]],"date-time":"2025-09-20T01:16:33Z","timestamp":1758330993000},"source":"Crossref","is-referenced-by-count":0,"title":["Toxicity-benefit analysis of advanced prostate cancer trials using weighted toxicity scoring"],"prefix":"10.1093","volume":"30","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2748-4681","authenticated-orcid":false,"given":"Jaspreet K","family":"Gill","sequence":"first","affiliation":[{"name":"Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5,","place":["Canada"]},{"name":"Biological Sciences Platform, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0955-8396","authenticated-orcid":false,"given":"Rubens C","family":"Sperandio","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5,","place":["Canada"]},{"name":"Temerty Faculty of Medicine, University of Toronto , Toronto, ON M5S 1A8,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3204-0579","authenticated-orcid":false,"given":"Tuan","family":"Hoang","sequence":"additional","affiliation":[{"name":"Temerty Faculty of Medicine, University of Toronto , Toronto, ON M5S 1A8,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3178-1896","authenticated-orcid":false,"given":"Urban","family":"Emmenegger","sequence":"additional","affiliation":[{"name":"Division of Medical Oncology, Odette Cancer Centre, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5,","place":["Canada"]},{"name":"Biological Sciences Platform, Sunnybrook Health Sciences Centre , Toronto, ON M4N 3M5,","place":["Canada"]},{"name":"Temerty Faculty of Medicine, University of Toronto , Toronto, ON M5S 1A8,","place":["Canada"]},{"name":"Institute of Medical Science, University of Toronto , Toronto, ON M5S 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