PD-L1 expression in bladder cancer: Which scoring algorithm in what tissue? Schulz Gerald Bastian,Todorova Rumyana,Braunschweig Till,Rodler Severin,Volz Yannic,Eismann Lennert,Pfitzinger Paulo,Jokisch Friedrich,Buchner Alexander,Stief Christian,Mayr Doris,Casuscelli Jozefina Urologic oncology 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. 10.1016/j.urolonc.2021.06.001

Predictive Value of Combined Positive Score and Tumor Proportion Score for Immunotherapy Response in Advanced NSCLC. JTO clinical and research reports Introduction:In advanced-stage NSCLC, tumor proportion score (TPS) is typically used to predict the efficacy of immune checkpoint inhibitors (ICIs). Nevertheless, in other cancer types, the combined positive score (CPS), which covers programmed death-ligand 1 (PD-L1) expression on both tumor and surrounding immune cells, is used. We investigated the predictive value of CPS in comparison to TPS in advanced NSCLC. Methods:A monocenter, retrospective study was performed in patients with advanced NSCLC treated with ICI monotherapy between 2015 and 2021. Hematoxylin and eosin and PD-L1 were stained on baseline tumor biopsy samples to score PD-L1 by both TPS and CPS. Positivity for TPS and CPS was defined as a score of 1% or above. Progression-free survival and overall survival (OS) were assessed for TPS and CPS scores. Results:Among the 187 included patients, PD-L1 positivity was found in 112 patients (59.9%) by TPS and 135 patients (72.2%) by CPS. There was no significant difference in OS between TPS and TPS patients ( = 0.20). Nevertheless, CPS patients did have a longer OS than CPS patients ( = 0.006). OS was superior in both TPS/CPS and TPS/CPS as compared with TPS/CPS cases ( = 0.018 and  = 0.015, respectively), whereas no considerable differences in OS were found between TPS/CPS and TPS/CPS cases. Conclusions:This retrospective real-world population study revealed that CPS differentiated OS better than TPS in patients with advanced NSCLC with ICI monotherapy. Remarkably, this was driven by the performance of the TPS/CPS subgroup, indicating that CPS may be a better predictive biomarker for ICI efficacy. 10.1016/j.jtocrr.2023.100532

PD-L1 Immunohistochemistry in Gastric Cancer: Comparison of Combined Positive Score and Tumor Area Positivity Across 28-8, 22C3, and SP263 Assays. JCO precision oncology PURPOSE:The clinical application of PD-L1 immunohistochemistry (IHC) testing is complicated by the availability of multiple IHC assays, scoring algorithms, and cutoffs. This study assessed the analytical comparability of three commercially available PD-L1 assays and two scoring algorithms used to assess PD-L1 status in gastric cancer (GC) samples. METHODS:Serial sections of 100 resected GC samples, with PD-L1 expression levels across the dynamic range, were stained with three in vitro diagnostic-grade PD-L1 assays (28-8, 22C3, and SP263). Three trained pathologists blindly and independently scored slides using combined positive score (CPS) and tumor area positivity (TAP) algorithms. Comprehensive statistical analyses were performed to evaluate analytical concordance. Digital image analysis (DIA) was used to objectively compare the technical performance of each assay by simulating CPS and TAP. RESULTS:Comparable staining patterns were observed with these three PD-L1 assays. Despite discernible variation in staining intensity, reproducible evaluations of PD-L1 positivity were observed. Inter- and intra-assay assessments of all three assays, using either CPS or TAP and the same PD-L1 cutoffs, demonstrated moderate to almost-perfect (interassay Cohen's kappa [κ] range, 0.47-0.83) and substantial to almost-perfect (intra-assay κ range, 0.77-1.00) agreement. Interpathologist assessment exhibited a significant level of concordance (intraclass correlation coefficient ≥0.92). No difference in technical performance was observed using DIA. CONCLUSION:This study highlights analytical concordance in PD-L1 testing between three major PD-L1 assays when TAP and CPS are applied. Comparability of the technical assay performance was further supported by independent DIA. These observations support cross-application flexibility of the different PD-L1 assays and scoring algorithms to characterize PD-L1 expression in GC. 10.1200/PO.24.00230

Tumor Area Positivity (TAP) score of programmed death-ligand 1 (PD-L1): a novel visual estimation method for combined tumor cell and immune cell scoring. Diagnostic pathology BACKGROUND:Determination of programmed death-ligand 1 (PD-L1) protein expression level in tumor cells and tumor-associated immune cells is critical for identifying patients eligible for immunotherapy. PD-L1 manual scoring algorithms can generally be divided into two categories: cell counting and visual estimation. Cell counting can be time-consuming and is not in sync with pathology practice, which classically uses a Gestalt approach based on pattern recognition and visual estimation. In this study, we introduce the Tumor Area Positivity (TAP) score, which is a novel, straightforward method for scoring tumor cells and immune cells together using visual estimation. METHODS:To demonstrate the reproducibility of TAP scoring among pathologists, between- and within-reader precision studies were performed both within (internal) and outside of (external) our organization. We also compared the TAP score to the Combined Positive Score (CPS), which is based on cell counting, for concordance and time efficacy. RESULTS:The average positive agreement, average negative agreement, and overall percent agreement between and within readers were all above 85% for both internal and combined external reader precision studies. TAP score had high concordance rate at 5% cutoff compared with CPS at cutoff 1: positive percent agreement, negative percent agreement, and overall percent agreement were all above 85%. CONCLUSIONS:Our study showed the TAP scoring method to be straightforward, significantly less time-consuming, and highly reproducible with a high concordance rate between TAP score and CPS. 10.1186/s13000-023-01318-8