Programmed cell death-1 expression in BCG relapsing tumors is significantly associated with stage progression in non-muscle invasive bladder cancer patients
Sources of Funding: none
Introduction
The programmed cell death-1 (PD-1) pathway has been suggested to play an important role in tumor immune escape. We evaluated the change of PD-1 expression before and after BCG therapy and its prognostic significance in non-muscle invasive bladder cancer (NMIBC) patients.
Methods
We evaluated 78 matched tissue samples of NMIBC in both previous tumors before BCG therapy and BCG-relapsing tumors, which was defined as recurrence after achieving a disease-free status by initial BCG instillations for 6 months. We counted PD-1 positive tumors infiltrating lymphocytes under x200 magnification immunohistochemically and when the number of PD-1 positive cells was more than 18, PD-1 expression was defined as high.
Results
The median follow-up interval after BCG relapse was 81 months. The median number of PD-1 positive cells in previous tumors just before BCG therapy was 3.5, which was significantly lower than that in BCG-relapsing tumors (17.0, p<0.001). High PD-1 expression was observed in 20 previous tumors just before BCG therapy (25.6%) and 36 BCG-relapsing tumors (46.2%). An increase in PD-1 expression after BCG therapy was observed in 52 cases (66.6%, Figure A). After excluding 10 muscle invasive bladder cancers at the time of BCG-relapsing, subsequent stage progression was noted in 8 (11.8%). Kaplan-Meier curves showed that the 5-year progression-free survival rate was 74.1% in patients with PD-1 high expression in BCG-relapsing tumors, which was significantly lower than that in patients with PD-1 low expression (94.1%, p=0.042, Figure B). Multivariate Cox regression analysis showed that PD-1 high expression (HR=8.27, p=0.033) was an independent risk factor for stage progression.
Conclusions
PD-1 was induced by BCG therapy and PD-1 expression in BCG-relapsing tumor might be an important indicator for predicting stage progression in NMIBC.
Funding
none
Eiji Kikuchi
Shuji Mikami
Nozomi Hayakawa
Akira Miyajima
Mototsugu Oya