Programmed Death-ligand 1 (PD-L1) Expression in Bladder Cancer and its Correlation with Tumor Grade, Stage, and Outcome

Abstract

Objectives: To evaluate the expression of programmed death-ligand 1 (PD-L1) in bladder cancer cases in Oman using immunohistochemistry, and to determine whether the level of PD-L1 expression is associated with tumor grade, stage, or outcome. An additional objective was to identify the clinicopathological features of bladder cancer among Omanis. Methods: This was a retrospective cohort study of patients where we subjected archived tissue samples to prospective analysis. All patients diagnosed and treated for bladder cancer in Sultan Qaboos University Hospital from January 2006 to December 2017 and followed up for at least one year were included. Clinical and demographical information of the patients was obtained from their medical records. PD-L1 testing using immunohistochemistry was performed on formalin-fixed paraffin-embedded tissue blocks. Scoring of PD-L1 expression by tumor cells was conducted independently by two pathologists. Positivity was defined using two different cut-off values (≥ 5% and ≥ 25%) of tumor cells showing membrane or cytoplasmic staining. The outcome was divided into two categories either no recurrence at the last follow-up, or recurrence/disease progression/death. Results: There were 68 cases of bladder cancer; 72.1% were male; the age range was 35–89 years (mean = 65.3 and median = 66). The largest number of patients were diagnosed with stage II cancer (38.8%) followed by stage I cancer (32.8%). Hematuria was the most common presentation (58.7%). High-grade tumors were seen in 83.8% (57/68) of patients. Invasive urothelial carcinoma appeared in 79.4% (54/68). PD-L1 tests were performed on 63 cases where tissue blocks were available. PD-L1 was positive in 44.4% of cases using a cut-off value of 5%; however, it dropped to 30.2% at a cut-off value of 25%. At the cut-off value of 5%, PD-L1 was significantly associated with tumor grade (p =0.033), but the significance was lost when the cut-off value of 25% was applied (p =0.250). No significant association was found between PD-L1 expression and outcome using both cut-off values and stage at diagnosis (p =0.798 and p =0.102, respectively).Conclusions: This study showed that at a cut-off value of ≥ 5%, 44.4% of cases of bladder cancer were PD-L1 positive. There was a significant association between PD-L1 expression in bladder cancer and tumor grade. No statistically significant association was found between tumor stage and outcome. The results indicated the potential benefit of anti-PD-L1 immunotherapy for patients with high tumor grades.

Keywords

• bladder cancer
• programmed death ligand 1
• pd-l1 inhibitors
• oman