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Schulz, Gerald Bastian; Todorova, Rumyana; Braunschweig, Till; Rodler, Severin; Volz, Yannic; Eismann, Lennert; Pfitzinger, Paulo; Jokisch, Friedrich; Buchner, Alexander; Stief, Christian; Mayr, Doris and Casuscelli, Jozefina (2021): PD-L1 expression in bladder cancer: Which scoring algorithm in what tissue? In: Urologic Oncology-Seminars and Original Investigations, Vol. 39, No. 10, 734.e1

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Introduction: For cisplatin-ineligible patients, approval of first-line immune-checkpoint inhibitor therapy relies on the programmed death ligand 1 (PD-L1) expression assay employed, namely, the combined positive score (CPS) or immune cell (IC) score. This study compares PD-L1 diagnostic scores and positivity in primary and matched metastatic bladder cancer tissue. Methods: A total of 108 patients undergoing radical cystectomy for urothelial bladder cancer and lymphatic spread (pN+) were included. PD-L1 expression was compared by immunohistochemistry (IHC) between the primary bladder tumor and associated lymph node metastases using Ventana SP263 anti-PD-L1 antibody. In a subset of cases further IHC was performed with Ventana SP142 and Dako 22C3 antibodies. Second, the PD-L1 scoring algorithms for the CPS and IC score were compared. Correlation of PD-L1 positivity with clinical parameters and tumor stage was assessed. Intra-and intertissue analyses were performed with Pearson's chi square test, McNemar test and Spearman correlation employing IBM SPSS 25. Results: PD-L1 expression did not correlate with clinicopathological parameters. The CPS (43.5% vs. 35.6%;P=0.006) and the IC score (28.7% vs. 21.2%;P=0.002) yielded PD-L1 positivity significantly more often in primary BC than in matched lymph node metastasis. Both the CPS (r=0.775;P<0.001) and the IC score (r=0.711;P<0.001) correlated between primary and metastatic bladder cancer tissue. Employing CPS vs. IC led to significantly more PD-L1-positive classified cases in primary BC (CPS vs. IC;43.5% vs. 28.7%;P<0.001) and lymph node metastasis (CPS vs. IC;35.6% vs. 21.2%, P<0.001). Conclusion: Compared to lymph node analysis, bladder tissue yields more PD-L1 positivity assessed with the CPS and IC scores. This is particularly evident when employing the CPS. The findings highlight that employing both PD-L1 assays may maximize eligibility for first-line checkpoint-inhibitors to treat bladder cancer patients unfit for cisplatin-based chemotherapy. (C) 2021 Elsevier Inc. All rights reserved.

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