College of Medicine and Public Health, Flinders University, Adelaide, Australia.
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
Clin Genitourin Cancer. 2022 Apr;20(2):132-138. doi: 10.1016/j.clgc.2021.11.010. Epub 2021 Dec 2.
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.
Cox proportional hazard analysis were used to validate overall survival (OS) discrimination performance of the 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 the Bellmunt score. External validation of an enhanced Bellmunt score utilized the independent atezolizumab arm of IMvigor211.
In IMvigor210, Bellmunt score displayed moderate OS discrimination (c = 0.66). Addition of CRP (one point for CRP>30 mg/L) to the 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.
CRP inclusion within the Bellmunt score enhanced the ability to discriminate high risk patients misclassified using the original 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.
贝伦蒙特风险评分（Bellmunt score）对免疫检查点抑制剂（ICI）治疗的预测效能尚未明确。本研究旨在验证和提高贝伦蒙特评分在接受ICI 治疗的尿路上皮癌患者中的预后预测能力。
采用 Cox 比例风险分析验证了贝伦蒙特评分在接受阿替利珠单抗治疗的 IMvigor210 研究尿路上皮癌患者中的总生存（OS）预测效能。采用 C 统计量（c）评估 C 反应蛋白（CRP）、中性粒细胞与淋巴细胞比值（NLR）、乳酸脱氢酶（LDH）、肿瘤浸润免疫细胞 PD-L1 基因表达水平（PD-L1 ICs）、白蛋白、前次化疗时间和肿瘤部位数量对贝伦蒙特评分的校正作用。采用 IMvigor211 研究中阿替利珠单抗单臂数据进行外部验证。
在 IMvigor210 研究中，贝伦蒙特评分对 OS 有中等程度的预测效能（c=0.66）。CRP（CRP＞30mg/L 记 1 分）的加入可使评分的预测效能最佳提高（c=0.70），其次为 NLR（c=0.69）。外部验证中，CRP-贝伦蒙特评分较原始贝伦蒙特评分（OS：c=0.64，PFS：c=0.59）具有更好的预测效能（OS：c=0.67，PFS：c=0.60），30%的患者被重新归入高风险组。CRP-贝伦蒙特评分 0、1、2、3 分的患者 1 年 OS 率分别为 63%、44%、21%和 15%。
CRP 的加入可提高贝伦蒙特评分对患者的区分能力，使更多患者被重新归入高风险组。我们建议 CRP-贝伦蒙特评分可提高ICI 临床试验中高危患者的分层能力，为接受 ICI 治疗的尿路上皮癌患者提供更准确的预后信息。
