Heterogeneity of PD-L1 expression between primary and metastatic bladder cancer tumors and therapeutic implications between the immune cell score and combined positivity score.

Abstract

e17041 Background: Heterogeneity of PD-L1 expression between primary and metastatic tumors has been reported for different cancer entities. In metastatic bladder cancer (BC), this might have an impact on therapeutic algorithms. For cisplatin-ineligible patients, first-line immune-checkpoint inhibitor therapy is recommended based on the PD-L1 expression assay employed, namely immune cell (IC) or combined positive score (CPS). Here, we compared the CPS and IC scores in bladder tumors (BT) and matched metastatic lymph nodes (LN). Methods: From our institutional database we identified patients with urothelial BC and lymphatic spread on pathologic examination of radical cystectomy specimens. Both CPS and IC were assessed by PD-L1 immunohistochemistry in the BT and matched LN metastases. Positive scores were in accordance to the respective cut-offs (CPS ≥10 and IC ≥2). Key clinicopathological parameters were correlated with CPS and IC scores. Differences between the two scores and between primary BT and LN metastasis were compared. CPS and IC scores both between and within the bladder tumour and LN metastasis were tested for correlation. Finally, the prognostic impact of the CPS and IC score was assessed. Pearson’s chi-squared test, Wilcoxon-test and Log-rank test were employed. Results: We included 108 patients (73.1% males, 26.9% females) with LN-positive urothelial BC. There was no correlation between age, gender, T-stage, number of positive lymph nodes and either CPS or IC scores. CPS was significantly more often positive in BT specimens (43.5%, n = 47/108) compared to LN samples (35.6%, n = 37/104) (p = 0.004). IC score was also significantly more often positive in BT specimens (28.7%, n = 31/108) compared to LN samples (21.2%, n = 22/104) (p = 0.013). There are significantly more CPS positive vs. IC positive cases when assessing PD-L1 expression in BT (p < 0.001). CPS and IC score positively correlated within both BT (r = 0.682, p < 0.001) and LN (r = 0.648, p < 0.001). CPS (r = 0.778, p < 0.001) and IC (r = 0.692, p < 0.001) positively correlated between the bladder tumour and LN. PD-L1 expression had no impact on oncological prognosis. Conclusions: PD-L1 expression measured by CPS correlates with IC scores in BC. There are, however, significant and clinically relevant differences between the BT and LN as well as between the two assays. Besides the implication for checkpoint-inhibitor therapy, PD-L1 expression does not seems to be prognostic in BC.