Impact of Programmed Death-ligand 1 Expression on Oncological Outcomes in Patients with Muscle-invasive Bladder Cancer Treated with Radiation-based Therapy

Abstract

BackgroundNo biomarkers are recommended for patients undergoing radiation-based therapy (RT) for muscle-invasive bladder cancer (MIBC). ObjectiveWe aim to evaluate the predictive role of programmed death-ligand 1 (PD-L1) expression on the oncological outcomes of patients treated with RT for MIBC. Design, setting, and participantsA single-center retrospective analysis of tumor specimens collected through transurethral resection (TURBT) from 104 MIBC patients, implemented in a tissue microarray and stained with the SP263 PD-L1 clone (Ventana Medical Systems, Tucson, AZ, USA), was conducted. Two reviewers measured the PD-L1 H-score for tumor and immune cells. InterventionRT (maximal TURBT followed by radiation and concurrent chemotherapy when eligible). Outcome measurements and statistical analysisLogistic and Cox regression models were used to predict 3-mo complete response (CR) and overall survival (OS) after RT, respectively. Results and limitationsA total of 88 (85%) patients had cT2 disease and 39 (37.5%) had high immune cell PD-L1 expression. A CR was achieved in 68 (65%) patients. On the multivariable analysis (MVA), a higher clinical stage (p = 0.02) and a low immune cell PD-L1 H-score (p = 0.02) were associated with a decreased CR after RT. The median time to death was 43 mo (95% confidence interval 20–66). On Cox MVA, a high immune cell PD-L1 H-score (p = 0.0017) was associated with better OS, independently of performance status (p = 0.0005) or tumor stage (p = 0.0013). A high tumor cell PD-L1 H-score was not an independent predictor of CR or OS. Limitations of the study include the retrospective design. ConclusionsMIBC patients with high PD-L1 expression on immune cells appear to have better oncological outcomes following RT. Our results may aid in patient stratification for future clinical trial design. Patient summaryIn this report, we evaluated the role of programmed death-ligand 1 (PD-L1) expressed on tumor and immune cells in the tumor microenvironment for patients treated with a bladder-sparing regimen. We found that PD-L1 overexpression on immune cells is able to predict a better response to radiation-based therapy.