Background

Programmed death-ligand 1 (PD-L1) positivity is associated with poor prognosis in renal cell carcinoma (RCC). Because the prognostic impact and effect of confounding factors are less known, we investigated the prognostic significance of PD-L1 expression in Japanese patients with recurrent/metastatic RCC who started systemic therapy in 2010–2015.

Methods

This multicenter, retrospective study recruited patients from 29 Japanese study sites who had prior systemic therapy for RCC (November 2018 to April 2019) and stored formalin-fixed paraffin-embedded primary lesion samples. The primary outcome was overall survival (OS) by PD-L1 expression. Secondary outcomes included OS in subgroups and duration of first- and second-line therapies by PD-L1 expression. OS distributions were estimated using Kaplan–Meier methodology.

Results

PD-L1 expression (on immune cells [IC] ≥ 1%) was observed in 315/770 (40.9%) patients. PD-L1 positivity was more prevalent in patients with poor risk per both Memorial Sloan Kettering Cancer Center [MSKCC] and International Metastatic RCC Database Consortium, and high-risk pathological features (higher clinical stage, nuclear grade and sarcomatoid features). Median OS for PD-L1–positive patients was 30.9 months (95% CI 25.5–35.7) versus 37.5 months (95% CI 34.0–42.6) for PD-L1–negative patients (HR 1.04 [90% CI 0.89–1.22, p = 0.65]; stratified by MSKCC risk and liver metastases). Propensity score weight (PSW)-adjusted OS was similar between PD-L1–positive and –negative patients (median 34.4 versus 31.5 months; estimated PSW-adjusted HR 0.986).

Conclusions

This study suggests PD-L1 status was not an independent prognostic factor in recurrent/metastatic RCC during the study period because PD-L1 positivity was associated with poor prognostic factors, especially MSKCC risk status.

中文翻译：

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日本肾细胞癌患者程序性死亡配体 1 状态的预后价值

背景

程序性死亡配体 1 (PD-L1) 阳性与肾细胞癌 (RCC) 的不良预后相关。由于混杂因素的预后影响和影响鲜为人知，我们研究了 2010-2015 年开始全身治疗的日本复发/转移性 RCC 患者中 PD-L1 表达的预后意义。

方法

这项多中心、回顾性研究从 29 个日本研究中心招募了既往接受过 RCC 全身治疗（2018 年 11 月至 2019 年 4 月）的患者，并储存了福尔马林固定石蜡包埋的原发灶样本。主要结果是 PD-L1 表达的总生存期 (OS)。次要结果包括亚组中的 OS 以及 PD-L1 表达的一线和二线治疗持续时间。使用 Kaplan-Meier 方法估计 OS 分布。

结果

在 315/770 (40.9%) 名患者中观察到 PD-L1 表达（在免疫细胞上 [IC] ≥ 1%）。PD-L1 阳性在纪念斯隆凯特琳癌症中心 [MSKCC] 和国际转移性 RCC 数据库联盟的低风险和高风险病理特征（更高的临床分期、核分级和肉瘤样特征）的患者中更为普遍。PD-L1 阳性患者的中位 OS 为 30.9 个月（95% CI 25.5–35.7），而 PD-L1 阴性患者的中位 OS 为 37.5 个月（95% CI 34.0–42.6）（HR 1.04 [90% CI 0.89–1.22，p  = 0.65]；按 MSKCC 风险和肝转移分层）。PD-L1 阳性和阴性患者的倾向评分权重 (PSW) 调整后的 OS 相似（中位数 34.4 个月对 31.5 个月；估计 PSW 调整后的 HR 0.986）。

结论

该研究表明 PD-L1 状态不是研究期间复发/转移性 RCC 的独立预后因素，因为 PD-L1 阳性与预后不良因素相关，尤其是 MSKCC 风险状态。