PD-L1 expression in tumor and inflammatory cells is associated with favorable tumor features and favorable prognosis in muscle-invasive urothelial carcinoma of the bladder not treated by immune checkpoint inhibitors

Background A high level of PD-L1 expression is the most relevant predictive parameter for response to immune checkpoint inhibitor (CPI) therapy in urinary bladder cancer.

Existing data on the relationship between PD-L1 expression and the natural course of disease are controversial and sparse.

Methods To expand our understanding of the relationship between PD-L1 expression and parameters of cancer aggressiveness, PD-L1 was analyzed on tissue microarrays containing 2710 urothelial bladder carcinomas including 512 patients with follow-up data who underwent radical cystectomy and follow-up therapies in the pre-immune checkpoint inhibitor therapy era.

Results Tumor cell positivity in ≥10% of cells were seen in 513 (20%) and an immune cell positivity occurred in 872 (34%) of 2566 interpretable cancers.

PD-L1 positivity in tumor cells increased from pTaG2 low grade (0.9% positive) to pTaG3 high grade (4.1%; p  = 0.0255) and was even higher in muscle-invasive (pT2–4) carcinomas (29.3%; p  < 0.0001).

However, within pT2–4 carcinomas, PD-L1 positivity was linked to low pT stage ( p  = 0.0028), pN0 (p < 0.0001), L0 status ( p  = 0.0005), and a better prognosis within 512 patients with cystectomy who never received CPIs ( p  = 0.0073 for tumor cells and p  = 0.0086 for inflammatory cells).

PD-L1 staining in inflammatory cells was significantly linked to PD-L1 staining in tumor cells ( p  < 0.0001) and both were linked to a positive p53 immunostaining (p < 0.0001).

Conclusion It cannot be fully excluded that the strong statistical link between PD-L1 status and favorable histological tumor features as well as better prognosis could influence the outcome of studies evaluating CPIs in muscle-invasive urothelial carcinoma.