Immunotherapy in Bellini Duct Carcinoma: A Systematic Review

Background: Collecting duct carcinoma (CDC; Bellini duct carcinoma) is a rare, aggressive renal cancer with no established standard of care, and evidence for immune checkpoint inhibitor (ICI)-based therapy in CDC remains emerging and fragmented. We aimed to systematically synthesise efficacy and safety data on immunotherapy in adult patients with CDC. Methods: PubMed and Web of Science were searched from inception to 29 March 2025, with targeted post-search monitoring of key journals and ClinicalTrials.gov updated on 11 April 2026. Prospective interventional studies, observational cohorts/registries, and case series/reports were eligible. Screening, extraction and risk-of-bias appraisal (Joanna Briggs Institute tools) were performed independently in duplicate; results were narratively synthesised. Results: Overall, ICIs-particularly combinations-showed clinically meaningful activity in a subset of CDC patients. Twenty-four studies met criteria (2 prospective trials, 8 observational cohorts, 14 case-level publications/16 patients). The SUNNIFORECAST randomised phase II trial reported a CDC-specific ORR of 40% with ipilimumab + nivolumab versus 20% with standard of care (n = 9 CDC). Observational evidence yielded ORR ~10-44% and mOS ~13-42 months depending on regimen, with the highest activity seen with ICI plus TKI combinations. Durable complete responses (≥3-6 years) were documented at case level with dual checkpoint blockade and anti-PD-1 monotherapy. Safety was generally manageable, though serious events occurred sporadically (immune-mediated hepatitis; one fatal pneumonia). Conclusions: ICIs-particularly combination strategies-demonstrate clinically meaningful activity in selected patients with CDC, but evidence is limited by small samples, heterogeneity and high risk of bias. Prospective, biomarker-informed CDC-dedicated trials and coordinated registries are needed.