PD-L1 expression in high-risk non-muscle invasive bladder cancer is not a biomarker of response to BCG
Florus C. de Jong, Vebjørn Kvikstad, Robert F. Hoedemaeker, Angelique C. J. van der Made, Thierry P. van der Bosch, Niels J. van Casteren, Kim E.M. van Kessel, Ellen C. Zwarthoff, Joost L. Boormans, Tahlita C.M. Zuiverloon
Abstract
PURPOSE: Up to 50% of high-risk non-muscle invasive bladder cancer (HR-NMIBC) patients fail Bacillus Calmette-Guérin (BCG) treatment, resulting in a high risk of progression and poor clinical outcomes. Biomarkers that predict outcomes after BCG are lacking. The antitumor effects of BCG are driven by a cytotoxic T cell response, which may be controlled by immune checkpoint proteins like Programmed Death Ligand 1 (PD-L1). Here, we hypothesized that PD-L1 protein expression could serve as a biomarker for BCG-failure. METHODS: HR-NMIBC patients who received ≥ 5 BCG instillations were included. Tissue microarrays were constructed from BCG-naïve tumors and recurrences and stained with the PD-L1 (SP142) antibody. PD-L1 status was defined as ≥ 5% tumor-infiltrating immune cells with membrane staining in the tumor area. Clinicopathological associations with PD-L1 positive tumors were investigated, and time-to-event analyses were performed comparing PD-L1 positive vs. negative tumors. RESULTS: 432 BCG-naïve tumors and 160 recurrences were included, and 91% of patients received adequate BCG. In BCG-naïve tumors, PD-L1 was expressed in 7% of patients and PD-L1 expression was associated with stage T1 versus Ta disease (p = 0.015). PD-L1 expression was not associated with treatment failure after adequate BCG (p = 0.782) nor with progression-free survival (p = 0.732). Testing cut-offs of ≥ 1% and ≥ 10% PD-L1 positivity did not alter results. High PD-L1 expression was more frequent in tumor recurrences (14%) as compared to BCG-naïve tumors (p = 0.012). CONCLUSION: PD-L1 expression in HR-NMIBC is not a biomarker of response to BCG. However, PD-L1 is higher in a subset of tumors that failed BCG treatment. More research is needed to determine the role of PD-L1 in tumors where BCG treatment failed.