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

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 s...

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Main Authors: Lorena Incorvaia, Sarah Scagliarini, Fernando Sabino Marques Monteiro, Hideki Takeshita, Jose Carlos Tapia, María Natalia Gandur Quiroga, Elaine Lam, Deniz Tural, Lazar Popovic, Saul Campos-Gomez, Paolo Andrea Zucali, Augusto Mota, Cinzia Ortega, Juan Pablo Sade, Mimma Rizzo, Ondřej Fiala, Nuno Vau, Patrizia Giannatempo, Halima Abahssain, Andrea Benedetto Galosi, Giuseppe Badalamenti, Jindrich Kopecky, Aristotelis Bamias, Johannes Landmesser, Jawaher Ansari, Fabio Calabrò, Francesco Massari, Sebastiano Buti, Joaquim Bellmunt, Matteo Santoni
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Language:English
Published: Nature Portfolio 2025-03-01
Series:Scientific Reports
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Online Access:https://doi.org/10.1038/s41598-025-93094-2
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author Lorena Incorvaia
Sarah Scagliarini
Fernando Sabino Marques Monteiro
Hideki Takeshita
Jose Carlos Tapia
María Natalia Gandur Quiroga
Elaine Lam
Deniz Tural
Lazar Popovic
Saul Campos-Gomez
Paolo Andrea Zucali
Augusto Mota
Cinzia Ortega
Juan Pablo Sade
Mimma Rizzo
Ondřej Fiala
Nuno Vau
Patrizia Giannatempo
Halima Abahssain
Andrea Benedetto Galosi
Giuseppe Badalamenti
Jindrich Kopecky
Aristotelis Bamias
Johannes Landmesser
Jawaher Ansari
Fabio Calabrò
Francesco Massari
Sebastiano Buti
Joaquim Bellmunt
Matteo Santoni
author_facet Lorena Incorvaia
Sarah Scagliarini
Fernando Sabino Marques Monteiro
Hideki Takeshita
Jose Carlos Tapia
María Natalia Gandur Quiroga
Elaine Lam
Deniz Tural
Lazar Popovic
Saul Campos-Gomez
Paolo Andrea Zucali
Augusto Mota
Cinzia Ortega
Juan Pablo Sade
Mimma Rizzo
Ondřej Fiala
Nuno Vau
Patrizia Giannatempo
Halima Abahssain
Andrea Benedetto Galosi
Giuseppe Badalamenti
Jindrich Kopecky
Aristotelis Bamias
Johannes Landmesser
Jawaher Ansari
Fabio Calabrò
Francesco Massari
Sebastiano Buti
Joaquim Bellmunt
Matteo Santoni
author_sort Lorena Incorvaia
collection DOAJ
description 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.
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spelling doaj-art-56d24ec802e447bd9c9995e0b420ddf42025-08-20T02:56:09ZengNature PortfolioScientific Reports2045-23222025-03-011511910.1038/s41598-025-93094-2Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumabLorena Incorvaia0Sarah Scagliarini1Fernando Sabino Marques Monteiro2Hideki Takeshita3Jose Carlos Tapia4María Natalia Gandur Quiroga5Elaine Lam6Deniz Tural7Lazar Popovic8Saul Campos-Gomez9Paolo Andrea Zucali10Augusto Mota11Cinzia Ortega12Juan Pablo Sade13Mimma Rizzo14Ondřej Fiala15Nuno Vau16Patrizia Giannatempo17Halima Abahssain18Andrea Benedetto Galosi19Giuseppe Badalamenti20Jindrich Kopecky21Aristotelis Bamias22Johannes Landmesser23Jawaher Ansari24Fabio Calabrò25Francesco Massari26Sebastiano Buti27Joaquim Bellmunt28Matteo Santoni29Department of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of PalermoUOC di Oncologia, Azienda Ospedaliera di Rilievo Nazionale Cardarelli di NapoliLatin American Cooperative Oncology Group - LACOGDepartment of Urology, Saitama Medical Center, Saitama Medical UniversityDepartment of Medical Oncology, Institut d’Investigació Biomèdica Sant Pau, Hospital de la Santa Creu i Sant PauHospital Ángel H. Roffo, CABAUniversity of Colorado Anschutz Medical CampusDepartment of Medical Oncology, Bakirköy Dr. SadiKonuk Training and Research HospitalOncology Institute of Vojvodina, Faculty of Medicine, University Novi SadCentro Oncologico Estatal ISSEMYMDepartment of Oncology, IRCCS Humanitas Research HospitalClínica AMOMichele and Pietro Ferrero Hospital - ASL CN2Instituto Alexander Fleming, CABADivision of Medical Oncology, A.O.U. Consorziale Policlinico di BariDepartment of Oncology and Radiotherapeutics, Faculty of Medicine and University Hospital in Pilsen, Charles UniversityUrologic Oncology, Champalimaud Clinical CenterDipartimento di Oncologia Medica, Fondazione IRCCS Istituto Nazionale dei TumoriMedical Oncology Unit, Medicine and Pharmacy Faculty, National Institute of Oncology, Mohamed V UniversityUrology Unit, Azienda Ospedaliero-Universitaria delle Marche, Università Politecnica delle MarcheDepartment of Precision Medicine in Medical, Surgical and Critical Care (Me.Pre.C.C.), Section of Medical Oncology, University of PalermoDepartment of Clinical Oncology and Radiotherapy, University Hospital Hradec Kralove2nd Propaedeutic Department of Internal Medicine, ATTIKON University Hospital, School of Medicine, National and Kapodistrian University of AthensKlinik Für UrologieMedical Oncology, Tawam HospitalMedical Oncology 1, IRCCS Regina Elena National Cancer InstituteMedical Oncology, IRCCS Azienda Ospedaliero-Universitaria di BolognaMedical Oncology Unit, University Hospital of ParmaDana Farber Cancer Institute, Harvard Medical SchoolOncology Unit, Macerata HospitalAbstract 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.https://doi.org/10.1038/s41598-025-93094-2ImmunotherapyNCT05290038PembrolizumabSex differencesUrothelial Cancer
spellingShingle Lorena Incorvaia
Sarah Scagliarini
Fernando Sabino Marques Monteiro
Hideki Takeshita
Jose Carlos Tapia
María Natalia Gandur Quiroga
Elaine Lam
Deniz Tural
Lazar Popovic
Saul Campos-Gomez
Paolo Andrea Zucali
Augusto Mota
Cinzia Ortega
Juan Pablo Sade
Mimma Rizzo
Ondřej Fiala
Nuno Vau
Patrizia Giannatempo
Halima Abahssain
Andrea Benedetto Galosi
Giuseppe Badalamenti
Jindrich Kopecky
Aristotelis Bamias
Johannes Landmesser
Jawaher Ansari
Fabio Calabrò
Francesco Massari
Sebastiano Buti
Joaquim Bellmunt
Matteo Santoni
Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
Scientific Reports
Immunotherapy
NCT05290038
Pembrolizumab
Sex differences
Urothelial Cancer
title Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
title_full Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
title_fullStr Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
title_full_unstemmed Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
title_short Sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
title_sort sex as modifier of survival in patients with advanced urothelial cancer treated with pembrolizumab
topic Immunotherapy
NCT05290038
Pembrolizumab
Sex differences
Urothelial Cancer
url https://doi.org/10.1038/s41598-025-93094-2
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