PD-L1+ CTCs Are Associated with Adverse Pathological Features and Unfavorable Prognosis in Bladder Cancer

Backgrounds: As one of the important liquid biopsy methods in recent years, circulating tumor cells (CTCs) have been proven to be valuable in judging metastasis and prognosis in various tumors. With the advent of immunotherapy, the expression of programmed death-ligand 1 (PD-L1) on CTCs has also attracted researchers' attention, but its value in bladder cancer has not been fully explored. Methods: This study enrolled patients diagnosed with urothelial carcinoma who were treated in the Department of Urology, The First Affiliated Hospital of Nanjing Medical University from 2020 to 2023. Peripheral blood samples of the patients were collected to detect PD-L1+ CTCs. Meanwhile, the patients' basic clinical characteristics, pathological data, and follow-up information were collected. The Kaplan-Meier method was used to estimate the overall survival (OS) and progression-free survival (PFS) of the patients, and the log-rank test was employed to evaluate the statistical differences. COX regression analysis and Firth penalized Cox regression analysis were adopted to assess the risk factors. Finally, according to the clinical or pathological characteristics, the effects of PD-L1+/PD-L1- CTCs on different subgroups of the population were evaluated, respectively. Results: According to the inclusion and exclusion criteria, a total of 109 patients were finally enrolled in this study, including 95 males and 16 females, with a median age of 68 years. The expression of PD-L1 on CTC was as follows: 19 patients were PD-L1+ CTC and 90 patients were PD-L1- CTCs. The results showed that the pathological grade of patients with PD-L1+ CTCs was significantly higher than that of patients with PD-L1- CTCs (p = 0.003). With a median follow-up time of 48 months (IQR: 45.8-49.5), prognostic analysis indicated that PD-L1+ CTCs were a risk factor for OS in bladder cancer patients (HR = 4.696 (1.477-13.596), p = 0.011). Subgroup analysis revealed that in patients with non-muscle-invasive bladder cancer (NMIBC) and in the subgroup of patients with high pathological grade, those with PD-L1+ CTCs exhibited significantly poorer prognosis in terms of PFS and OS compared with patients with PD-L1- CTCs. Conclusions: The presence of PD-L1+ CTCs in patients with bladder carcinoma may be closely associated with high-grade disease and poor OS.