Enhanced Bellmunt risk score for survival prediction in urothelial carcinoma treated with immunotherapy

Introduction : The discrimination performance of Bellmunt risk score for immune checkpoint inhibitor (ICI) therapy is largely unknown. This study aimed to validate and enhance discrimination of the Bellmunt score in patients with urothelial carcinoma treated with ICIs. Patients and methods : Cox proportional hazard analysis was used to validate overall survival (OS) discrimination performance of Bellmunt score in patients with urothelial carcinoma treated with atezolizumab in IMvigor210. The c-statistic (c) was used to evaluate the ability of C-reactive protein (CRP), neutrophil-to-lymphocyte ratio (NLR), lactate dehydrogenase (LDH), PD-L1 gene expression level on immune cells (PD-L1 ICs), albumin, time from prior chemotherapy, and tumor site count to enhance Bellmunt score. External validation of an enhanced Bellmunt score utilized independent atezolizumab arm of IMvigor211. Results : In IMvigor210, Bellmunt score displayed moderate OS discrimination (c=0.66). Addition of CRP (one point for CRP>30mg/L) to Bellmunt score resulted in greatest improvement in performance (c=0.70), followed by NLR (c=0.69). On external validation, CRP-Bellmunt score had superior performance (OS c=0.67, PFS c=0.60) than original Bellmunt score (OS c=0.64, PFS c=0.59) with 30% of patients reclassified into a higher risk group. Patients with CRP-Bellmunt score of 0, 1, 2, or 3-plus had 1-year OS probabilities of 63%, 44%, 21%, and 15%, respectively. Conclusions : CRP inclusion within Bellmunt score enhanced the ability to discriminate high risk patients misclassified using the original Bellmunt model. We propose that the CRP-Bellmunt score may enable improved patient stratification in ICI clinical trials and provide more accurate prognostic information for patients with urothelial carcinoma initiating ICIs. Micro Abstract The Bellmunt risk score is a well-recognized prognostic model in second-line urothelial carcinoma. However, its discrimination performance for immune checkpoint inhibitor (ICI) therapy is unclear. The present analysis indicates addition of one point for C-reactive protein (CRP>30mg/L) to Bellmunt score resulted in superior survival discrimination. The CRP-Bellmunt score will enable more accurate patient stratification in clinical trials and enhanced prognostic information for patients with urothelial carcinoma initiating ICIs.