Programmed Cell Death-Ligand 1 Expression Status in Urothelial Carcinoma According to Clinical and Pathological Factors: A Multi-Institutional Retrospective Study.

Hyung Suk Kim,Ja Yoon Ku,In Ho Chang,Sung Han Kim,Ja Hyeon Ku,Byong Chang Jeong,Hong Koo Ha,Won Sik Ham,Dong Hyun Lee,Se Young Choi,Seong Soo Jeon,Seung Il Jung,Wan Song,Ho Kyung Seo,Won Sik Jang,Taesoo Choi

doi:10.3389/fonc.2020.568809

Abstract

Purpose: To investigate programmed cell death-ligand 1 (PD-L1) expression status and the clinical and pathological factors related to its expression in urothelial carcinoma (UC) patients.Materials and Methods: Data from 761 UC patients who underwent testing for PD-L1 expression using the VENTANA (SP-142 immunohistochemistry assay) for measuring PD-L1 expression according to the manufacturer's protocol between February 2016 and July 2019 were retrospectively reviewed. Patients were categorized into three groups based on the percentage of tumor area covered by PD-L1-expressing tumor-infiltrating immune cells (ICs) as follows: IC0 (<1%), IC1 (≥1% and <5%), and IC2/3 (≥5%). Positive PD-L1 expression was defined as IC2/3 (≥5%). The factors related to positive PD-L1 expression were assessed by using unadjusted and adjusted logistic regression analyses.Results: In the entire cohort, 213 (28%) patients showed positive PD-L1 expression. Final adjusted regression analyses for positive PD-L1 expression revealed that several factors, including intravesical BCG prior to PD-L1 testing (odds ratio [OR] 0.57, 95% confidence interval [CI] 0.37–0.96), advanced tumor stage (stage III/IV) (OR 2.04, 95% CI 1.41–2.93), and high tumor grade (OR 5.31, 95% CI 2.38–11.83) were significantly associated with positive PD-L1 expression.Conclusions: This study showed that the PD-L1 expression is associated with several clinical and pathological factors for the first time in a real-world setting. Further follow-up clinical trials should consider adjusting these factors, including intravesical BCG treatment, tumor stage and grade to clarify the utility of PD-L1 as a biomarker.

Highlights

Immune checkpoints, such as programmed cell death-1 (PD1) and its associated ligand (PD-L1), have attracted significant attention as major protein targets for systemic immunotherapy of a number of solid tumors, including urothelial carcinoma (UC) [1]
The KEYNOTE-045 study of pembrolizumab found no association between objective response rate and combined positive score (CPS) for PDL1 expression, but the KEYNOTE-052 study did in first line [2, 8]
We aimed to identify the PD-L1 expression status using the VENTANA (SP142) test which was used as a companion diagnostic test for atezolizumab in Korea and the factors significantly associated with positive PDL1 expression

Summary

Introduction

Immune checkpoints, such as programmed cell death-1 (PD1) and its associated ligand (PD-L1), have attracted significant attention as major protein targets for systemic immunotherapy of a number of solid tumors, including urothelial carcinoma (UC) [1]. On the basis of the efficacy and safety identified in these clinical trials, five PD-1(pembrolizumab, nivolumab)/PDL1(atezolizumab, durvalumab, and avelumab) inhibitors have been recommended for first or second-line use in the treatment of locally advanced or metastatic UC by international guidelines [10]. PD-L1 expression has been suggested as a potential biomarker for predicting the response to and prognosis following ICI therapy in UC patients [2,3,4,5,6,7,8,9, 15,16,17,18,19,20,21,22,23]. The KEYNOTE-045 study of pembrolizumab found no association between objective response rate and combined positive score (CPS) for PDL1 expression, but the KEYNOTE-052 study did in first line [2, 8]

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