Department of Urology, Caritas St. Josef Medical Center, University of Regensburg, Landshuter Str. 65, 93053, Regensburg, Germany.
STRATIFYER Molecular Pathology GmbH, Cologne, Germany.
Cancer Immunol Immunother. 2018 Mar;67(3):403-412. doi: 10.1007/s00262-017-2093-9. Epub 2017 Nov 17.
Checkpoint inhibition has emerged as new therapeutic option in muscle-invasive bladder cancer. The objective of the present study was to evaluate the prognostic role of PD1 and PDL1 expression in non-muscle-invasive bladder cancer (NMIBC) and establish an objective measuring method using RNA quantification.
We retrospectively analyzed clinical data and formalin-fixed paraffin-embedded tissues (FFPE) of patients with stage pT1 NMIBC who underwent transurethral resection of the bladder. mRNA expression of PD1, PDL1 and CD3 was measured by single step RT-qPCR and correlated to clinicopathological parameters, recurrence-free survival (RFS), progression-free survival (PFS) and carcinoma-specific survival (CSS).
We have analyzed 334 patients with NMIBC at stage pT1 for mRNA analysis. Data from 296 patients (79% male, median age: 72 years) could be used. Spearman correlation revealed significant associations between mRNA expressions of PD1/PDL1 (ρ: 0.6024, p < 0.0001), CD3/PDL1 (ρ: 0.5728, p < 0.0001) and CD3/PD1 (ρ: 0.7005, p < 0.0001). Kaplan-Meier analysis revealed that high PDL1 mRNA expression (≥ 33.83) is a favorable prognostic factor with regard to better RFS (p = 0.0018), PFS (p = 0.021) and CSS (p = 0.012). Multivariate Cox-regression analysis proved PDL1 expression to be an independent prognosticator for RFS [HR 0.48 (0.31-0.72), p = 0.0005], PFS [HR 0.45 (0.24-0.80), p = 0.0059] and CSS [HR 0.31 (0.13-0.67), p = 0.0021].
High mRNA expression of PDL1 predicts improved RFS, PFS and CSS of pT1 NMIBC. Following prospective validation, this objective measurement of PD-L1 might help stratify patients with NMIBC for immunotherapy and identify patients who might benefit from early cystectomy.
检查点抑制已成为肌层浸润性膀胱癌的新治疗选择。本研究的目的是评估 PD1 和 PDL1 表达在非肌层浸润性膀胱癌（NMIBC）中的预后作用，并建立一种使用 RNA 定量的客观测量方法。
我们回顾性分析了接受经尿道膀胱肿瘤切除术的 pT1NMIBC 患者的临床数据和福尔马林固定石蜡包埋组织（FFPE）。通过一步 RT-qPCR 测量 PD1、PDL1 和 CD3 的 mRNA 表达，并将其与临床病理参数、无复发生存（RFS）、无进展生存（PFS）和癌特异性生存（CSS）相关联。
我们对 334 名 pT1 期 NMIBC 患者进行了 mRNA 分析。296 名患者（79%为男性，中位年龄：72 岁）的数据可用于分析。Spearman 相关性分析显示 PD1/PDL1（ρ：0.6024，p<0.0001）、CD3/PDL1（ρ：0.5728，p<0.0001）和 CD3/PD1（ρ：0.7005，p<0.0001）的 mRNA 表达之间存在显著相关性。Kaplan-Meier 分析显示，高 PDL1 mRNA 表达（≥33.83）是 RFS（p=0.0018）、PFS（p=0.021）和 CSS（p=0.012）较好的有利预后因素。多变量 Cox 回归分析证实 PDL1 表达是 RFS 的独立预后因素[HR 0.48（0.31-0.72），p=0.0005]、PFS [HR 0.45（0.24-0.80），p=0.0059]和 CSS [HR 0.31（0.13-0.67），p=0.0021]。
PDL1 的高 mRNA 表达预测 pT1NMIBC 的 RFS、PFS 和 CSS 改善。在前瞻性验证后，这种 PD-L1 的客观测量可能有助于对 NMIBC 患者进行免疫治疗分层，并识别可能从早期膀胱切除术受益的患者。
