Optimal duration of immune checkpoint inhibitor therapy in genitourinary cancers: A systematic review and meta-analysis of real-world studies.

470 Background: Immune checkpoint inhibitors (ICIs) have transformed the management of genitourinary (GU) malignancies, producing durable responses in renal cell carcinoma (RCC) and urothelial carcinoma (UC). However, the optimal duration of ICI therapy and the durability of response after discontinuation remain uncertain. In clinical practice, decisions to stop ICIs are often individualized, based on response or toxicity, with no standardized approach. This systematic review is to evaluate real-world outcomes—including treatment-free survival (TFS), overall survival (OS), and progression-free survival (PFS)—after ICI discontinuation in patients with GU cancers. Methods: A systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify real-world studies reporting outcomes following ICI discontinuation in RCC and UC. Eligible studies included patients who discontinued therapy after achieving an objective response (complete response [CR], partial response [PR], or stable disease [SD]) or due to treatment-related adverse events (TRAEs). Data on TFS, OS, PFS, and duration of ICI therapy were extracted and analyzed descriptively. Studies lacking survival endpoints were excluded from the pooled analysis. Results: Twenty retrospective studies met the inclusion criteria, comprising 611 patients with GU cancers. Among these, 253 (41.4%) discontinued ICIs for TRAEs, and 191 (31.3%) underwent elective discontinuation. Overall, 262 patients (58%) achieved an objective response (CR/PR) and 114 (25.4%) achieved SD. Ten studies were excluded from the pooled analysis due to inconsistent endpoints or incomplete TFS data. Ten studies were included in the pooled analysis. Of these, five studies (127 patients) reported median OS, five studies (126 patients) reported median PFS, and six studies (126 patients) reported median TFS. The median duration of ICI therapy was 6.1 months. Pooled analysis revealed a median TFS of 13.3 months (95% CI: 8.6–18.0), median PFS of 7.4 months (95% CI: 1.8–13.0), and median OS of 19.0 months (95% CI: 2.1–35.0). Conclusions: This systematic review highlights the durability of disease control after ICI discontinuation in advanced GU cancers. Many patients maintained prolonged responses off therapy, suggesting potential for finite-duration immunotherapy in selected responders. However, the wide confidence intervals and study heterogeneity underscore the need for larger, prospective studies to define the optimal duration of ICI therapy and identify predictors of sustained benefit.