Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy
Prognostic significance of pre- and post-treatment PD-L1 expression in patients with primary high-grade non-muscle-invasive bladder cancer treated with BCG immunotherapy
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DOI：
10.1007/s00345-019-03065-2
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发表时间：
2020-01-03
影响因子：
3.4
通讯作者：
Bilen, Cenk Y.
中科院分区：
文献类型：
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作者：
Aydin, Ahmet Murat;Baydar, Dilek E.;Bilen, Cenk Y.
目的 程序性细胞死亡 1 配体 1 (PD-L1) 表达与泌尿系统恶性肿瘤的预后相关。我们的目的是研究接受 BCG 治疗的高级别非肌层浸润性膀胱癌 (NMIBC) 患者治疗前和治疗后 PD-L1 表达的预后意义。方法 我们回顾了 2004 年至 2017 年间总共 141 例接受经尿道切除术 + >= 6 次 BCG 滴注治疗的高级别 NMIBC 病例。PD-L1 免疫组织化学 (IHC) 评分按 0-3 级进行，阳性和高水平 PD-L1 表达的截止值分别设置为肿瘤浸润免疫细胞 (IC) 染色 >= 1% 和 >= 5%。比较临床病理特征和肿瘤学结果 [无复发 (RFS) 和无进展生存 (PFS)]，并按 PD-L1 阳性进行分层。使用 Kaplan-Meier 以及单变量和多变量 Cox 回归分析评估 PD-L1 的预后作用。结果治疗前，高级别 NMIBC 中分别有 46.2% 和 6.8% 表现出阳性和高水平 PD-L1 表达。 PD-L1 阳性表达与粘膜下浸润和难治性肿瘤复发相关。在回归分析中，PD-L1 表达与 RFS 或 PFS 无关。治疗后，55.1% 和 11.6% 的复发肿瘤分别表现出阳性和高水平的 PD-L1 表达。难治性复发患者中 PD-L1 表达下调（p = 0.012）。结论 原发性高级别 NMIBC 治疗前 PD-L1 表达水平与不良病理特征相关，且难治性复发患者接受 BCG 免疫治疗后 PD-L1 表达水平显着降低。 PD-L1表达对于PFS或RFS没有预后价值；因此，有必要进一步研究以确定新的生物标志物来预测高级别 NMIBC 的疾病结果。
Purpose Programmed cell death-1 ligand-1 (PD-L1) expression has been associated with prognostic implications in urologic malignancies. We aimed to investigate prognostic significance of pre- and post-treatment PD-L1 expression in patients treated with BCG for high-grade non-muscle-invasive bladder cancer (NMIBC). Methods We reviewed a total of 141 high-grade NMIBC cases treated with transurethral resection + >= 6 BCG instillations between 2004 and 2017. PD-L1 immunohistochemistry (IHC) scoring was done on 0-3 scale, and cut-off for positive and high-level PD-L1 expression was set to >= 1% and >= 5% staining of tumor-infiltrating immune cells (IC), respectively. Clinicopathologic characteristics and oncologic outcomes [recurrence-free (RFS) and progression-free survival (PFS)] were compared, stratified by PD-L1 positivity. The prognostic role of PD-L1 was assessed using Kaplan-Meier, and univariate and multivariate Cox regression analyses. Results Pre-treatment, 46.2% and 6.8% of high-grade NMIBC demonstrated positive and high-level PD-L1 expression, respectively. Positive PD-L1 expression was associated with submucosal invasion and refractory-tumor recurrence. PD-L1 expression was not associated with RFS or PFS in regression analysis. Post-treatment, 55.1% and 11.6% of recurrent tumors demonstrated positive and high-level PD-L1 expression, respectively. Down-regulation of PD-L1 expression was noted in patients with refractory recurrence (p = 0.012). Conclusion Pre-treatment PD-L1 expression was associated with unfavorable pathological features in primary high-grade NMIBC and its expression level after BCG immunotherapy was significantly decreased in patients with refractory recurrence. PD-L1 expression did not have prognostic value for PFS or RFS; therefore, further research is necessary to identify novel biomarkers for prediction of disease outcomes in high-grade NMIBC.