Predictive and Prognostic Role of PD-L1 in Urothelial Carcinoma Patients with Anti-PD-1/PD-L1 Therapy: A Systematic Review and Meta-Analysis

Haoran Liu, Tao Ye, Xiaoqi Yang, Peng Lv, Xiaoliang Wu, Hui Zhou, Hongyan Lu, Kun Tang, Zhangqun Ye, Haoran Liu, Tao Ye, Xiaoqi Yang, Peng Lv, Xiaoliang Wu, Hui Zhou, Hongyan Lu, Kun Tang, Zhangqun Ye

Abstract

Recently, checkpoint inhibition of the PD-1/PD-L1 axis has been shown to be therapeutically relevant in urothelial carcinoma (UC). To evaluate the predictive and prognostic value of PD-L1 on response and survival in UC patients after cystectomy, chemotherapy, or anti-PD-1/PD-L1 therapy, a systematic review of PubMed, Embase, Web of Science, and the Cochrane Library was performed. A total of 2154 patients from 14 published studies were included. In all UC patients after cystectomy, tumour cell (TC) PD-L1 expression was not associated with the OS or PFS. For the subset of patients with organ-confined disease, TC PD-L1 expression significantly predicted OS after cystectomy (P = 0.0004). There was no significant evidence of an association between TC PD-L1 status and ORR or OS for UC patients treated with platinum-based chemotherapy. For UC patients treated with anti-PD-1/PD-L1 therapy, TC PD-L1 expression ≥ 5% could predict the response (P = 0.005), but not for the 1% cut-off (P ≥ 0.05). As for PD-L1 expression in tumour-inflating immune cells (TIICs), both subsets with IC2/3 vs. IC0/1 and IC1/2/3 vs. IC0 were associated with ORR to anti-PD-1/PD-L1 therapy. In the TIIC subset, IC2/3 vs. IC0/1 of PD-L1 was associated with higher CR (P = 0.002), PR (P = 0.04), and PD (P = 0.007). Further, higher TIIC PD-L1 status benefited from longer PFS (P < 0.001), but was not associated with OS in UC patients with anti-PD-1/PD-L1 therapy. Our study suggested that TIIC PD-L1 expression with 5% cut-off was valuable as a predictive and prognostic biomarker for ORR and PFS in UC patients with anti-PD-1/PD-L1 therapy.

Conflict of interest statement

The authors have declared no competing interests.

Copyright © 2020 Haoran Liu et al.

Figures

Figure 1
Figure 1
Flow diagram for study selection.
Figure 2
Figure 2
Forest plots of tumour cell PD-L1 expression predicted (a) OS, (b) CSS, and (c) DFS for all UC patients after cystectomy. PD-L1: programmed death-ligand 1; +/-: positive/negative; OS: overall survival; CSS: cancer-specific survival; DFS: disease-free survival; CI: confidence interval.
Figure 3
Figure 3
Forest plots of tumour cell PD-L1 expression for predicting (a) OS, (b) CSS, and (c) DFS for patients with organ-confined tumours after cystectomy. PD-L1: programmed death-ligand 1; +/-: positive/negative; OS: overall survival; CSS: cancer-specific survival; DFS: disease-free survival; CI: confidence interval; IV: inverse variance; SE: standard error.
Figure 4
Figure 4
Forest plots of tumour cell PD-L1 status for predicting the (a) response and (b) prognosis to platinum-based chemotherapy in UC patients. PD-L1: programmed death-ligand 1; +/-: positive/negative; ORR: objective response rate; OS: overall survival; CI: confidence interval; M-H: Mantel-Hansel; SD: standard deviation.
Figure 5
Figure 5
Forest plots of (a) immune cell and (b) tumour cell PD-L1 status with cut-off values of 5% and 1% in predicting the response to anti-PD-1/PD-L1 immunotherapy. PD-L1: programmed death-ligand 1; ORR: objective response rate; IC: immune cell; CI: confidence interval; M-H: Mantel-Hansel; SD: standard deviation.
Figure 6
Figure 6
Forest plots of tumour cell PD-L1 status with cut-off values of 5% and 1% in predicting the (a) CR, (b) PR, (c) SD, and (d) PD to anti-PD-1/PD-L1 immunotherapy. PD-L1: programmed death-ligand 1; CR: completed response; PR: partial response; SD: stable disease; PD: progressive disease; CI: confidence interval; M-H: Mantel-Hansel; SD: standard deviation.
Figure 7
Figure 7
Forest plots of immune cell PD-L1 status with cut-off values of 5% and 1% in predicting the (a) CR, (b) PR, (c) SD, and (d) PD to anti-PD-1/PD-L1 immunotherapy. PD-L1: programmed death-ligand 1; IC: immune cell; CR: completed response; PR: partial response; SD: stable disease; PD: progressive disease; CI: confidence interval; M-H: Mantel-Hansel; SD: standard deviation.
Figure 8
Figure 8
Forest plots of immune cell PD-L1 status with cut-off values of 5% and 1% in predicting the (a) PFS and (b) OS for UC patients with anti-PD-1/PD-L1 immunotherapy. PD-L1: programmed death-ligand 1; IC: immune cell; PFS: progression-free survival; OS: overall survival; CI: confidence interval; IV: inverse variance; SD: standard deviation.

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