Nabil Ismaili, Sanaa El Majjaoui
Immunotherapy has become a cornerstone of urological oncology. Current paradigms include early ICI/ADC intensification in bladder cancer, ICI-based combinations in renal cell carcinoma, and the gradual integration of vaccines and checkpoint inhibitors in prostate cancer. Real-world evidence and immunoradiotherapy represents an emerging frontier, though optimal fractionation and sequencing require further investigation. Despite major advances, challenges remain in overcoming resistance, optimizing sequencing, and ensuring equitable access.
INTRODUCTION: The therapeutic landscape of urological cancers has undergone a paradigm shift with the advent of immunotherapy. This systematic review synthesizes clinical trials that have established new standards of care, complemented by evidence on immunotherapy-radiotherapy combinations and real-world data.
METHODS: A comprehensive search of PubMed/MEDLINE and Embase (2010-2026) identified phase II/III trials evaluating ICIs, ADCs, vaccines, or cellular therapies, as well as immunoradiotehrapy, observational studies, and registries reporting real-world outcomes.
RESULTS: Fifty-three clinical trials met the inclusion criteria: bladder cancer (n=14), kidney cancer (n=21), and prostate cancer (n=18), complemented by immunoradiotherapy trials (n=20), and real-world evidence (n=19). In bladder cancer, perioperative durvalumab and Enfortumab Vedotin (EV) plus pembrolizumab improved outcomes in MIBC, and the EV+pembrolizumab combination became a frontline standard for metastatic disease. Disitamab vedotin plus toripalimab improved outcomes in HER2-expressing tumours, and ctDNA-guided adjuvant atezolizumab introduces precision therapy for molecular residual disease. Emerging immunoradiotherapy combinations showed promising bladder-sparing potential (CR rates 64-88%). In kidney cancer, dual ICI and ICI+TKI combinations demonstrated long-term survival benefits. The RAMPART trial introduced adjuvant durvalumab ± tremelimumab, while transcriptomic-guided therapy and treatment of rare translocation RCC emerged from 2025-2026 trials. In prostate cancer, sipuleucel-T remains the first approved cancer vaccine, while newer trials explored ICIs (durvalumab+tremelimumab) and personalized peptide vaccines. Biomarker-driven approaches emerged across all tumor types, including ctDNA-guided therapy in bladder cancer, KIM 1 in kidney cancer, and PD-L1/DDR status in prostate cancer. Immunoradiotherapy combinations demonstrated activity in mCRPC (CA184-043, 5-year OS 7.9% vs 2.7%) and oligometastatic RCC (RAPPORT, ORR 63%). Real-world evidence confirmed trial findings while revealing critical gaps in access, the prognostic dominance of performance status, and the potential for radiotherapy-immunotherapy synergy.
CONCLUSION: Immunotherapy has become a cornerstone of urological oncology. Current paradigms include early ICI/ADC intensification in bladder cancer, ICI-based combinations in renal cell carcinoma, and the gradual integration of vaccines and checkpoint inhibitors in prostate cancer. Real-world evidence and immunoradiotherapy represents an emerging frontier, though optimal fractionation and sequencing require further investigation. Despite major advances, challenges remain in overcoming resistance, optimizing sequencing, and ensuring equitable access.