Prognostic value of programmed death-ligand 1 status in Japanese patients with renal cell carcinoma

Abstract

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.

The Association of Tumor Immune Microenvironment of the Primary Lesion with Time to Metastasis in Patients with Renal Cell Carcinoma: A Retrospective Analysis

“…This report is based on an additional analysis of a dataset from a previous multicenter, retrospective study that compared overall survival (OS) by PD-L1 expression status in patients with recurrent or mRCC who had received systemic therapy (the ARCHERY study [ 14 ]). We investigated the differences in the TIME of the primary lesions between synchronous and metachronous mRCCs with different time intervals to metastasis.…”

“…Only patients whose formalin-fixed paraffin-embedded nephrectomy specimens could be obtained were registered in this retrospective study. Patients with other coexisting malignancies or those treated with checkpoint inhibitors as 1L systemic therapy were excluded [ 14 ].…”

Prognostic value of PD-L1 expression in recurrent renal cell carcinoma after nephrectomy: a secondary analysis of the ARCHERY study

“…In the ARCHERY study, patients with metastatic or recurrent RCC who started 1L treatment between January 2010 and December 2015 were enrolled [ 8 ]. Patients underwent either cytoreductive nephrectomy or radical nephrectomy for localized disease.…”

“…The eligibility for high risk was based on current ongoing phase 3 trials evaluating CPIs in high-risk localized RCC [ 6 ]. ARCHERY showed a correlation between PD-L1 expression and nuclear grade [ 8 ]. Of note, nuclear/Fuhrman grade was a risk factor in the four commonly used localized RCC prognostic models, including the MSKCC postoperative nomogram [ 3 ].…”

“…The prognostic impact of PD-L1 expression on tumor-infiltrating immune cells (IC) in patients with recurrent or metastatic RCC treated with systemic therapy was previously investigated in a retrospective study, ARCHERY [ 8 ]. Median OS for PD-L1-positive patients and PD-L1-negative patients was 30.9 months (95% CI 25.5, 35.7) and 37.5 months (95% CI 34.0, 42.6), respectively (HR 1.04; 90% CI 0.89, 1.22; P = 0.65]; stratified by Memorial Sloan Kettering Cancer Center [MSKCC] risk and liver metastases).…”