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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.
World Journal of Urology ( IF 2.8 ) Pub Date : 2020-01-03 , DOI: 10.1007/s00345-019-03065-2
Ahmet Murat Aydin 1, 2 , Dilek E Baydar 3 , Berk Hazir 1 , Berrin Babaoglu 4 , Cenk Y Bilen 1
Affiliation  

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.

中文翻译:

BCG免疫疗法治疗原发性高级别非肌肉浸润性膀胱癌患者治疗前和治疗后PD-L1表达的预后意义。

目的程序性细胞死亡1配体1(PD-L1)的表达与泌尿系统恶性肿瘤的预后相关。我们旨在研究用卡介苗治疗高级别非肌肉浸润性膀胱癌(NMIBC)的患者治疗前和治疗后PD-L1表达的预后意义。方法我们回顾性分析了2004年至2017年间经尿道切除+≥6 BCG输注治疗的141例高等级NMIBC病例。PD-L1免疫组化(IHC)评分以0-3评分,阳性和高分值均被截断PD-L1水平的表达分别设定为浸润肿瘤的免疫细胞(IC)的染色≥1%和≥5%。比较临床病理特征和肿瘤结局[无复发(RFS)和无进展生存期(PFS)],以PD-L1阳性分层。使用Kaplan-Meier以及单因素和多因素Cox回归分析评估PD-L1的预后作用。结果治疗前,分别有46.2%和6.8%的高级NMIBC表现出阳性和高水平的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不相关。治疗后,分别有55.1%和11.6%的复发性肿瘤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)。结论难治性复发患者治疗前PD-L1的表达与原发性高级别NMIBC的不良病理特征有关,BCG免疫治疗后其表达水平明显降低。PD-L1表达对PFS或RFS没有预后价值;因此,有必要进行进一步的研究以鉴定新的生物标志物,以预测高级NMIBC的疾病预后。
更新日期:2020-01-04
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