Impact of baseline renal function on the clinical outcomes and safety of adjuvant nivolumab in high-risk urothelial carcinoma: a multicenter retrospective real-world study

Abstract Background Adjuvant nivolumab prolongs disease-free survival (DFS) in patients with urothelial carcinoma (UC) after radical surgery; however, evidence in those with reduced baseline renal function is limited. We investigated the impact of baseline creatinine clearance (CCr) on DFS and immune-related adverse events (irAEs) in a multicentre real-world cohort. Methods We retrospectively reviewed 125 patients with UC who received adjuvant nivolumab after radical cystectomy or nephroureterectomy at six Japanese institutions. Baseline CCr at nivolumab initiation was calculated using the Cockcroft–Gault equation and used to classify patients into a Low CCr group (< 60 mL/min) and a High CCr group (≥ 60 mL/min). DFS, irAE incidence, and irAE-related treatment interruption or discontinuation were compared between the two renal function groups. Results Among 125 patients, 83 (66.4%) had low-CCr and 42 (33.6%) had high-CCr. Patients with low-CCr were older, had lower body mass index, and more frequently had upper tract UC. Low-CCr was associated with worse DFS in univariable analysis (hazard ratio [HR] 1.94, 95% confidence interval [CI] 1.04–3.65), but was not independently associated with DFS in the multivariable model (HR 1.40, 95% CI 0.71–2.78). Female sex and variant histology were associated with inferior DFS. The incidences of all-grade and grade ≥ 3 irAEs were numerically higher in the low-CCr group (49.4% vs. 40.5% and 22.9% vs. 11.9%, respectively) but did not reach statistical significance. In contrast, irAE-related treatment interruption was significantly more frequent in patients with low-CCr (34.9% vs. 14.3%, p = 0.024), whereas permanent discontinuation rates were similar between groups. Conclusions Baseline CCr < 60 mL/min was associated with worse DFS in univariable analysis but was not independently associated with DFS after adjustment for other clinicopathological factors in this multicenter retrospective cohort. Although low-CCr was not associated with a statistically significant increase in severe irAEs, numerically higher rates of severe events and more frequent treatment interruptions suggest that careful monitoring and individualized management may be considered for patients with reduced baseline renal function.