Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab

Sci Rep. 2025 Mar 14;15(1):8815. doi: 10.1038/s41598-025-93094-2.

Abstract

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.

Publication types

  • Multicenter Study
  • Observational Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Antibodies, Monoclonal, Humanized* / therapeutic use
  • Antineoplastic Agents, Immunological* / therapeutic use
  • Carcinoma, Transitional Cell* / drug therapy
  • Carcinoma, Transitional Cell* / mortality
  • Carcinoma, Transitional Cell* / pathology
  • Female
  • Humans
  • Immune Checkpoint Inhibitors / therapeutic use
  • Male
  • Middle Aged
  • Sex Factors
  • Treatment Outcome
  • Urinary Bladder Neoplasms* / drug therapy
  • Urinary Bladder Neoplasms* / mortality
  • Urinary Bladder Neoplasms* / pathology
  • Urologic Neoplasms* / drug therapy
  • Urologic Neoplasms* / mortality
  • Urologic Neoplasms* / pathology
  • Urothelium / pathology

Substances

  • pembrolizumab
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents, Immunological
  • Immune Checkpoint Inhibitors