Prognostic Utility of PD-L1 in Squamous Cell Carcinoma of the Bladder
There is growing interest in immunotherapy utilizing checkpoint inhibitors for treatment of bladder cancer. There have been no reports on the expression of programmed death ligand 1 (PD-L1) in squamous cell carcinoma (SCC) of the bladder. Herein, we assessed the relationship between PD-L1 expression and clinicopathological features and oncological outcomes in SCC.
Immunohistochemistry of PD-L1 was performed on 151 radical cystectomy specimens with pure SCC treated with radical cystectomy (RC) in Mansoura, Egypt from 1997 to 2003 with long term oncological outcomes. The relationship between PD-L1, pathological features, and oncological outcomes was analyzed.
The study included 151 cases of SCC (98 men) with a median age of 52 years (range: 36-74 years). Schistosoma was associated with 81% of SCC cases. Overall, 141 (93%) patients presented with ≥ T2 stage and 47% had high grade carcinoma. Positive expression of PD-L1 was found in 101 (67%) specimens. Negative expression of PD-L1 was associated with higher pathological T stage (p = 0.04) and grade (p = 0.01). The median length of follow-up after RC was 63 months (range: 1-100 months). Kaplan-Meier analyses (see Figures) showed that negative expression of PD-L1 is associated with both disease recurrence (p = 0.01) and bladder cancer-specific mortality (p = 0.01). In multivariate Cox proportional hazards regression analyses, negative expression of PD-L1 was an independent predictor of disease recurrence (HR 2.05, 95% CI 1.06 - 3.96, p = 0.03) and bladder cancer-specific mortality (HR 2.89, 95% CI 1.22 - 6.82, p = 0.02), after adjusting for tumor grade, pathologic tumor stage, lymph node involvement, and lymphovascular invasion.
Negative expression of PD-L1 is associated with higher tumor stage, tumor grade, and worse oncological outcomes after RC for SCC. This study suggests that higher expression of PD-L1 may be part of the immune response associated with better outcomes in SCC. Further studies are needed to elucidate if PD-L1 can be a predictor of response to immunotherapy for SCC.