Immune checkpoint inhibitors in advanced upper-tract urothelial carcinoma: a multicenter study

To evaluate real-world efficacy of anti-PD-(L)1 immune checkpoint inhibitors (ICIs) in advanced or metastatic upper-tract urothelial carcinoma (mUTUC) and identify clinical and biological factors associated with treatment outcomes, this multicenter retrospective study included 184 adult patients with progressive mUTUC from 16 centers who were treated with single-agent ICIs between 2016 and 2022. Primary endpoint was overall survival (OS). Secondary endpoints included response and progression-free survival (PFS). 90% had received previous platinum-based chemotherapy. OS was 27% (95% CI: 21–34) at 2 years and 13% (95% CI: 8–20) at 5 years. Median OS was 11 months (95% CI: 8.2–15). PFS was 23% (95% CI: 17–30) at 1 year and 13% (95% CI: 8.5–18) at 2 years. Median PFS was 2.5 months (95% CI: 2.2–2.8). 20% of patients had an objective response including 8.7% complete responses. Bellmunt risk factors and the Neutrophil-to-Lymphocyte Ratio retained strong prognostic value. In exploratory analyses, the small subgroup of patients with tumors harboring microsatellite instability ( n = 7) showed favorable outcomes, whereas FGFR genes alterations ( n = 16) were not associated with differential outcomes. ICIs demonstrate real-world efficacy in mUTUC comparable to that reported in pivotal trials and real-world cohorts of mUC including all primary tumor sites. Patient-centered clinical parameters have high prognostic value as in all-primary site UC population. Given its rich molecular landscape, biomarkers specific to mUTUC will be of interest in tailoring future ICI-based treatments.