Prognostic value of PD-L1 and PD-1 expression in upper tract urothelial carcinoma patients.

Abstract

To evaluate the prognostic value of PD-L1 and PD-1 expression in upper tract urothelial carcinoma (UTUC) patients. A retrospective multicenter study was conducted in 283 UTUC patients treated with radical nephroureterectomy (RNU) between 2000 and 2015 at 10 French hospitals. Immunohistochemistry analyses were performed using 2 mm-core tissue micro-arrays with NAT105® and 28.8® antibodies at a 5% cut-off for positivity on tumor cells and tumor-infiltrating lymphocytes to evaluate PD-L1 and PD-1 expression, respectively. Multivariable Cox regression models were used to determine the independent predictors of recurrence-free (RFS), cancer-specific (CSS) and overall survival (OS). Overall, 63 (22.3%) and 220 (77.7%) UTUC patients had PD-L1 positive and negative disease, respectively, while 91 (32.2%) and 192 (67.8%) had PD-1 positive and negative disease, respectively. Patients who expressed PD-L1 or PD-1 were more likely to have ≥pT2(68.3% vs. 49.5%;p=0.009 and 69.2% vs. 46.4%;p<0.001, respectively) and high-grade(90.5% vs. 70.0%;p=0.001 and 91.2% vs. 66.7%; p<0.001, respectively) disease with lymphovascular invasion(52.4% vs. 17.3%;p<0.001 and 39.6% vs. 18.2%;p<0.001, respectively) as compared to those who did not. In multivariable Cox regression analysis adjusting for each other, PD-L1 and PD-1 expression were significantly associated with decreased RFS (HR=1.83;95%CI=[1.09-3.08];p=0.023 and HR=1.59; 95%CI=[1.00-2.54];p=0.049; respectively), CSS (HR=2.73; 95%CI=[1.48-5.04]; p=0.001 and HR=1.96; 95%CI=[1.12-3.45]; p=0.019; respectively) and OS (HR=2.08;95%CI=[1.23-3.53]; p=0.006 and HR=1.71; 95%CI=[1.05-2.78];p=0.031; respectively). In addition, multivariable Cox regression analyses evaluating the four-tier combination of PD-L1 and PD-1 expression showed that only [PD-L1 / PD-1 positive] patients (n=38; 13.4%) had significantly decreased RFS (HR=3.07; 95%CI=[1.70-5.52];p<0.001), CSS (HR=5.23; 95%CI=[2.62-10.43];p<0.001) and OS (HR=3.07; 95%CI=[1.70-5.52]; p<0.001) as compared to those with [PD-L1 / PD-1 negative] disease (n=167; 59.0%). We observed that PD-L1 and PD-1 expression were both associated with adverse pathological features that translated into an independent and cumulative adverse prognostic value in UTUC patients treated with RNU.