Abstract
Background: Check-Mate 274 has demonstrated the disease-free survival (DFS) benefit of adjuvant nivolumab in surgically treated muscle-invasive bladder cancer (MIBC). Since immunotherapy represents an expensive treatment with potential side effects, a better understanding of patient-specific risks of disease progression might be useful for clinicians when weighing the indication for adjuvant nivolumab. Objective: To identify the criteria for risk stratification of disease progression among MIBC patients eligible for adjuvant nivolumab. Materials and methods: A single-institution, prospectively maintained database was queried to identify patients eligible for adjuvant nivolumab according to Check-Mate 274 criteria. To account for immortal bias, patients who died or were lost to follow-up within 3 months of undergoing a radical cystectomy (RC) were excluded. Kaplan-Meier and Cox regression analyses addressed DFS, defined as the time frame from diagnosis to the first documented recurrence or death from any cause, whichever occurred first. Regression tree analysis was implemented to identify criteria for risk stratification. Results: Between 2011 and 2022, 304 patients were identified, with a median follow-up of 50 (IQR 24-72) months. After multivariable adjustment, including NAC as a potential confounder, higher CCI (HR 1.56, 95%CI 1.10-2.21, p = 0.013), T stage (HR 2.06, 95%CI 1.01-4.17, p = 0.046), N stage (HR 1.73, 95%CI 1.26-2.38, p = 0.001) and presence of LVI (HR 1.52, 95%CI 1.07-2.15, p = 0.019) increased the risk of disease recurrence or death. Finally, a two-tier classification was developed. Here, five-year DFS rates were 56.1% vs. 18.1 for low vs. high risk (HR: 2.54, 95%CI 1.79-3.62, p < 0.001). Conclusions: The current risk classification, if externally validated on larger samples, may be useful when weighing the risk and benefit of adjuvant nivolumab treatment and making patients more aware about their disease and about the need for additional treatment after RC.