Homomultimeric FAP Inhibitor-Based Radioligands for Cancer Theranostics: Design Principles, Structure–Function Relationships, and Preclinical Performance

Zhiyang Wu

doi:10.3390/molecules31122124

Immunotherapy in urological cancers: new paradigms and a systematic review of clinical trials and real-world evidence

2026-08-12

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OA

AI

N

NI Nabil Ismaili *

S

SE Sanaa El Majjaoui

DOI：10.3389/fonc.2026.1871832

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IntroductionThe 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.MethodsA 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.ResultsFifty-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.ConclusionImmunotherapy 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.

Keywords:

prostate cancer

bladder cancer

immunotherapy

radiotherapy

immune checkpoint inhibitors

antibody-drug conjugates

kidney cancer

cancer vaccines

Immunotherapy in urological cancers: new paradigms and a systematic review of clinical trials and real-world evidence

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