Gender- and sex-based disparities in response to immune-checkpoint inhibitors (ICI) has been reported in a variety of tumor types. Women have different anatomy with recurrent urinary tract infections, a different sex hormonal profile, and intrinsic differences in local and systemic immune systems and urobiome composition. Existing literature data in a pan-cancer context reveal contradictory results, and real-world evidence in urothelial carcinoma (UC) is lacking. This was a real-world, multicenter, international, observational study to determine the sex effects on the clinical outcomes in metastatic urothelial carcinoma (mUC) patients progressing or recurring after platinum-based therapy and treated with pembrolizumab as a part of routine clinical care. A total of 1039 patients, treated from January 1st, 2016 to December 31st, 2023 in 68 cancer centers were included. Our data showed that women with metastatic urothelial carcinoma treated with pembrolizumab had shorter OS than men, with a 13% advantage in the 5-year OS rate for male patients. A deeper understanding of these results may inform sex-stratification in future prospective clinical trials and help develop strategies to reduce the magnitude of the sex disparities observed in urothelial cancer outcomes.

• Keywords
• Immunotherapy, NCT05290038, Pembrolizumab, Sex differences, Urothelial Cancer,
• MeSH
• Antibodies, Monoclonal, Humanized * therapeutic use   MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Carcinoma, Transitional Cell * drug therapy   mortality   pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   mortality   pathology   MeSH
• Antineoplastic Agents, Immunological * therapeutic use   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Sex Factors MeSH
• Urologic Neoplasms * drug therapy   mortality   pathology   MeSH
• Urothelium pathology   MeSH
• Treatment Outcome MeSH
• Check Tag
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Observational Study MeSH
• Names of Substances
• Antibodies, Monoclonal, Humanized * MeSH
• Immune Checkpoint Inhibitors MeSH
• pembrolizumab MeSH Browser
• Antineoplastic Agents, Immunological * MeSH