For advanced urothelial carcinoma treatment, immune checkpoint inhibitor regimens centered on the PD-1/PD-L1 signaling axis are now widely adopted as first-line core therapies. Nevertheless, reliable and clinically verified predictive biomarkers tailored for pathologically confirmed pathologically confirmed node-negative (pN0) patients with postoperative recurrence and distant metastasis are still lacking. This retrospective matched-cohort study aimed to investigate the prognostic and predictive significance of PD-1 expression on tumor-infiltrating lymphocytes (TILs) in pN0 bladder cancer patients treated with ICIs, with a focus on its role in guiding personalized treatment.

A total of 120 pN0 bladder cancer patients with postoperative recurrence or metastasis were enrolled. After 1:1 propensity score matching (PSM), 50 patients (25 per group) were included. CD8⁺ T cells, FOXP3⁺ Tregs, and serum IL-6, TNF-α, CRP levels were detected. Primary endpoints were objective response rate (ORR) and disease control rate (DCR); secondary endpoints included early progressive disease (EPD), progression-free survival (PFS), and overall survival (OS).

After PSM, the baseline characteristics of the two groups were well balanced. The high PD-1 expression group (≥ 5%) showed higher CD8⁺ T cell infiltration and CD8⁺/FOXP3⁺ ratio, as well as lower FOXP3⁺ Treg infiltration and serum inflammatory marker levels (all P < 0.01). The high-expression group had higher ORR (48.0% vs. 24.0%) and DCR (76.0% vs. 52.0%), lower EPD incidence (12.0% vs. 48.0%), and longer median PFS (8.1 vs. 4.3 months) and OS (21.9 vs. 13.7 months) (all P < 0.05). The predictive accuracy of PD-1 combined with CD8⁺/FOXP3⁺ ratio or IL-6 was higher than that of PD-1 alone (AUC 0.825 and 0.802 vs. 0.681, P < 0.05). High PD-1 expression was an independent protective factor for PFS (HR = 0.49) and OS (HR = 0.52).

High PD-1 expression in TILs is a potential independent candidate predictive biomarker for better favorable ICI response and survival outcomes in patients with pN0 recurrent/metastatic bladder cancer. Combining PD-1 with CD8⁺/FOXP3⁺ ratio or IL-6 enhances predictive accuracy, providing a basis for personalized immunotherapy. Due to the retrospective single-center design, limited sample size after PSM, and lack of full-cohort immune phenotyping to confirm PD-1 cellular origin, this biomarker remains a candidate indicator requiring further prospective multi-center validation.