Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
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.
Authors
- Ondřej Fiala (ORCID: https://orcid.org/0000-0002-4096-7385)
- Halima Abahssain (ORCID: https://orcid.org/0000-0002-3109-1609)
- Sebastiano Buti (ORCID: https://orcid.org/0000-0003-0876-0226)
- Fabio Calabrò (ORCID: https://orcid.org/0000-0002-7863-3540)
- Cinzia Ortega (ORCID: https://orcid.org/0000-0003-2628-7671)
- Matteo Santoni (ORCID: https://orcid.org/0000-0001-7340-6173)
- María Natalia Gandur Quiroga (ORCID: https://orcid.org/0000-0001-7034-0842)
- Nuno Vau
- Johannes Landmesser
- Mimma Rizzo (ORCID: https://orcid.org/0000-0001-7743-741X)
- Jindřich Kopecký (ORCID: https://orcid.org/0000-0002-4126-0410)
- Aristotelis Bamias (ORCID: https://orcid.org/0000-0002-5996-7262)
- Saúl Campos-Gómez (ORCID: https://orcid.org/0000-0002-1804-2589)
- José Carlos Tapia (ORCID: https://orcid.org/0000-0001-6545-8862)
- Juan Pablo Sade (ORCID: https://orcid.org/0009-0004-4038-7294)
- Giuseppe Badalamenti (ORCID: https://orcid.org/0000-0002-2478-8838)
- Lorena Incorvaia (ORCID: https://orcid.org/0000-0002-1199-7286)
- Paolo Andrea Zucali (ORCID: https://orcid.org/0000-0002-2274-1702)
- Francesco Massari (ORCID: https://orcid.org/0000-0001-6476-6871)
- Fernando Sabino Marques Monteiro (ORCID: https://orcid.org/0000-0002-6621-8251)
- Sarah Scagliarini (ORCID: https://orcid.org/0000-0001-5814-2296)
- Lazar Popović (ORCID: https://orcid.org/0000-0002-3278-6875)
- Joaquim Bellmunt (ORCID: https://orcid.org/0000-0003-2328-3421)
- Hideki Takeshita (ORCID: https://orcid.org/0000-0002-1512-6904)
- Elaine T. Lam (ORCID: https://orcid.org/0000-0001-5629-3402)
- Jawaher Ansari (ORCID: https://orcid.org/0000-0001-5525-548X)
- Patrizia Giannatempo (ORCID: https://orcid.org/0000-0002-3358-4466)
- Andrea Benedetto Galosi (ORCID: https://orcid.org/0000-0001-8313-5338)
- Augusto Mota
- Deniz Tural (ORCID: https://orcid.org/0000-0003-2144-6469)
Institutions
- Champalimaud Foundation (PT)
- Marche Polytechnic University (IT)
- University of Parma (IT)
- Humanitas University (IT)
- Harvard University (US)
- National and Kapodistrian University of Athens (GR)
- Charles University (CZ)
- Hospital de Sant Pau (ES)
- Eastern Cooperative Oncology Group (US)
- Tawam Hospital (AE)
- Oncology Institute of Vojvodina (RS)
- Dana-Farber Cancer Institute (US)
- Azienda USL di Bologna (IT)
- Bakırköy Dr.Sadi Konuk Eğitim ve Araştırma Hastanesi (TR)
- Instituto Alexander Fleming (AR)
- University Hospital Hradec Králové (CZ)
- Hospital Ana Nery (BR)
- Azienda di Rilievo Nazionale ed Alta Specializzazione (IT)
- Instituto de Salud del Estado de México (MX)
- Hospital Sírio-Libanês (BR)
- Istituti di Ricovero e Cura a Carattere Scientifico (IT)
- Fondazione IRCCS Istituto Nazionale dei Tumori (IT)
- Social Insurance Saitama Chuo Hospital (JP)
- IRCCS Humanitas Research Hospital (IT)
- Ospedale San Pietro Fatebenefratelli (IT)
- Ospedale di Macerata
- University of Colorado Anschutz Medical Campus (US)
- Saitama Medical University (JP)
- University of Palermo (IT)
Publication Details
- Journal
- Scientific Reports
- Published
- 2025-03-14
- DOI
- https://doi.org/10.1038/s41598-025-93094-2
- Citations
- 1
- Primary Topic
- Bladder and Urothelial Cancer Treatments
- Type
- article
- Field-Weighted Citation Impact
- 2.01