Trimodality therapy (TMT) is an accepted bladder-preserving option for selected patients with muscle-invasive bladder cancer (MIBC). Pembrolizumab has demonstrated activity in MIBC and may enhance the effects of chemotherapy and radiation.
We evaluated the safety and efficacy of adding pembrolizumab to TMT.
In this multicenter phase 2 trial, patients with MIBC received one dose of pembrolizumab followed by maximal transurethral resection, then definitive bladder radiation with concurrent low-dose gemcitabine and pembrolizumab every 3 wk for three doses. The primary end point was 2-yr bladder-intact disease-free survival (BIDFS). Secondary end points included safety, metastasis-free survival (MFS), and overall survival (OS).
Fifty-four patients were enrolled, including 48 in the efficacy cohort; 67% had clinical stage T2 disease. The 2-yr BIDFS was 60% (95% confidence interval [CI], 45-73). Two-yr MFS and OS were 81% (95% CI, 66-92) and 83% (95% CI, 69-91), respectively. Grade ≥3 treatment-related adverse events occurred in 25% of patients. Limitations include the single-arm design and modest sample size.
Pembrolizumab combined with gemcitabine-based chemoradiation was feasible and showed efficacy comparable to standard TMT. Ongoing phase 3 trials will further define its role in bladder preservation.
European urology. 2026 Apr 06 [Epub ahead of print]
Minas P Economides, Peter H O'Donnell, Ajjai S Alva, Matthew I Milowsky, Marisa Kollmeier, Scot Niglio, Jesse Persily, Randy F Sweis, Tracy Rose, Gopakumar Iyer, Daniel Spratt, Phillip Palmbos, Tsivia Hochman, Judith D Goldberg, Kaitlyn Francese, Sarah Griglun, Dayna Leis, Gary D Steinberg, James Wysock, Peter B Schiff, Nicholas J Sanfilippo, Samir S Taneja, David R Wise, William C Huang, Arjun V Balar
Laura and Isaac Perlmutter Cancer Center at NYU Langone Health and the NYU Grossman School of Medicine, New York, NY, USA. Electronic address: ., The University of Chicago Comprehensive Cancer Center, Chicago, IL, USA., University of Michigan Rogel Cancer Center, Ann Arbor, MI, USA., The University of North Carolina at Chapel Hill School of Medicine and UNC Lineberger Comprehensive Cancer Center, Chapel Hill, NC, USA., Memorial Sloan Kettering Cancer Center, New York, NY, USA., Department of Urology at NYU Langone Health and the NYU Grossman School of Medicine, New York, NY, USA., University Hospitals Seidman Cancer Center, Case Western Reserve University, Cleveland, OH, USA., Laura and Isaac Perlmutter Cancer Center at NYU Langone Health and the NYU Grossman School of Medicine, New York, NY, USA; Division of Biostatistics, Department of Population Health, NYU Grossman School of Medicine, New York, NY, USA., Laura and Isaac Perlmutter Cancer Center at NYU Langone Health and the NYU Grossman School of Medicine, New York, NY, USA., Department of Urology, Rush University Medical Center Chicago, IL, USA.
PubMed http://www.ncbi.nlm.nih.gov/pubmed/41945031