Abstract
Urothelial bladder cancer (UBC) patients ineligible to platinum-based chemotherapy can be treated with immune-checkpoint inhibitors (ICI) in Programmed Death Ligand 1 (PD-L1) positive cases. Although concordance exists between different PD-L1 assays, little is known on PD-L1 expression variability in matched UBC samples. We compared PD-L1 expression in whole slides of matched transurethral resections (TURBT), radical cystectomies (RC), and lymph node metastasis (LN). Immunohistochemistry using the VENTANA PD-L1 (SP263) assay was performed on 115 patients and scored positive if expression occurred in ≥25% immune cells (IC), ≥25% tumour cells (TC), or both. PD-L1 was positive in 42.7% TURBT, 39.8% RC, and 27.3% LN specimens. Concordance was moderate (κ=0.52; P<0.001) between TURBT and RC, and fair between LN and TURBT (κ=0.31; P=0.048) or RC (κ=0.25; P=0.075). Comparison with the VENTANA PD-L1 (SP142) assay which had been performed previously on the same cohort showed moderate to substantial inter-assay agreement (κ=0.42–0.66). Although TC staining is not part of the SP142 scoring algorithm, discordant PD-L1 assay outcome could be attributed to SP263 TC≥25% staining in only 41% of cases. These results show that PD-L1 expression variability between matched specimens is higher than that between individual assays. Optimal specimen determination for PD-L1 testing needs to be addressed in future studies.
Highlights
With a global annual incidence of 430,000 patients, bladder cancer is the fourth and tenth most common cancer in men and women, respectively [1]
Since Programmed Death Ligand 1 (PD-L1) testing is required for starting first-line treatment with atezolizumab and pembrolizumab in urothelial carcinoma, it is important to elucidate what assay and specimen type are most representative for prediction of therapeutic response
We found that PD-L1 status using the SP263 assay on whole tissue sections showed moderate agreement (κ=0.52) between TURBT and radical cystectomy (RC) specimens, and fair agreement (κ=0.25–0.31) between both specimens and lymph node metastasis (LN) metastasis
Summary
With a global annual incidence of 430,000 patients, bladder cancer is the fourth and tenth most common cancer in men and women, respectively [1]. From these patients, approximately 25% present with muscle-invasive bladder cancer (MIBC). According to American Urological Association (AUA) guidelines, neo-adjuvant cisplatin-based chemotherapy (NAC) followed by radical cystectomy (RC) is the recommended treatment for MIBC [2]. Despite this aggressive treatment regimen, the 5-year overall survival of MIBC patients is only 55%. The overall incidence and mortality rate have undergone little change in the past decades.
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