부산대학교 도서관

Simple Summary: While immunotherapy with checkpoint inhibitors is a standard component of treatment for advanced bladder cancer, its potential in early-stage, non-muscle-invasive bladder cancer (NMIBC) is increasingly being evaluated. Traditionally, NMIBC is managed with Bacillus Calmette–Guérin (BCG), a therapy that activates the immune system. Given that PD-L1 protein expression is an important marker for predicting the response to immunotherapy in advanced stages, and has shown prognostic value, and considering that BCG therapy functions by stimulating the immune system, our aim is to investigate whether PD-L1 levels change over time or with BCG treatment in high-risk NMIBC patients, and the prognostic implications thereof. This research could offer new insights into biomarker expression in early-stage bladder cancer by evaluating its susceptibility to therapies. The capacity of BCG to influence PD-L1 expression might provide hints for a sequential application of therapies. In the expanding landscape of immune checkpoint inhibitors (CPI) in high-risk (HR) non-muscle-invasive bladder cancer (NMIBC), the role of programmed death ligand 1 (PD-L1) as prognostic and predictive is increasingly significant. However, data evaluating its variability and susceptibility to Bacillus Calmette–Guérin (BCG) therapy in HR NMIBC patients is scarce. This retrospective study analyzed 126 HR NMIBC tissue samples from 63 patients (38× BCG-treated, 25× BCG-naïve) at two time points to assess PD-L1 expression using the 'combined positivity score' (CPS) with the 22C3 DAKO antibody method and correlated it with clinicopathological parameters. A CPS > 10 defined PD-L1 positivity. The impact of initial PD-L1 status and its change over time on time-to-recurrence, progression-free survival, and overall survival (TTR, PFS, OS) was analyzed using Kaplan–Meier and Cox proportional hazard models. BCG treatment significantly increased PD-L1 expression (5.31 vs. 0.22, p = 0.0423), with PD-L1 positive cases rising post-treatment in the BCG group and remaining unchanged in BCG-naïve patients. Multivariate analysis including T-stage, CIS, grading, tumor size, multifocality, age, and sex revealed a significant correlation between PD-L1 status change to positivity and improved TTR (p = 0.03). Our findings demonstrate a potential modulation of the PD-L1 status by an intravesical BCG therapy. However, its prognostic value appears limited. [ABSTRACT FROM AUTHOR]