2026/08/04 by Marie Christine Roesch, Lea Sophie Lütje, Marten Müller +3
paper · doi:10.1055/a-2897-1443
Abstract Treatment outcomes after systemic cancer therapies exhibit sex-specific differences. Real-world data do not necessarily reflect the results of randomized clinical trials (RCTs). To compare sex-specific outcomes between RCTs and subsequent real-world data in patients with urothelial cancer (UC) receiving systemic therapies. A systematic literature search on systemic therapies for UC was conducted in Embase, PubMed, MEDLINE, and Scopus up to February 2025. Eligible studies included phase II/III trials, RCTs, prospective non-interventional studies, retrospective studies, and case series. Extracted parameters comprised hazard ratios for overall survival and progression-free survival (or disease-free survival for adjuvant therapies), sex-specific enrollment rates, and discontinuation rates due to adverse effects. This review is registered with PROSPERO and was conducted in accordance with PRISMA guidelines. A total of 52 articles were included. The proportion of female patients enrolled in UC RCTs did not reflect epidemiologic data, and only a few real-world studies reached the expected benchmark. The following approval studies showed a survival benefit for men compared with women: JAVELIN Bladder 100 (Avelumab), Keynote 045 (Pembrolizumab), EV-301 (Enfortumab Vedotin), CheckMate 901 (Gemcitabine + Cisplatin + Nivolumab), and CheckMate 274 (adjuvant Nivolumab). Only a limited number of real-world studies reported sex-specific outcome analyses, and none demonstrated a clear benefit for either sex. No sex-specific toxicity analyses were published. Several approval studies investigating therapies for urothelial cancer suggest a survival benefit for male patients. However, this finding was not confirmed in real-world data. Female patients remain underrepresented in approval trials for UC, and sex-specific toxicity analyses are lacking. Such analyses should be mandatory in future RCTs.