The predictive value of PD-1 for the response to immune checkpoint inhibitor therapy in patients with bladder cancer without lymph node metastasis and its association with survival outcomes
4 affiliations
- 1Department of Urology, Urology & Nephrology Center, Zhejiang Provincial People’s Hospital(Affiliated People’s Hospital), Hangzhou Medical College, No.158, Shangtang Road, Hangzhou, Zhejiang Province 310000 China
- 2The Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, Zhejiang Province 310053 China
- 3Postgraduate Training Base Alliance of Zhejiang Provincial People’s Hospital, Wenzhou Medical University, Hangzhou, Zhejiang Province 310000 China
- 4The Second School of Clinical Medicine, Hangzhou Normal University, Hangzhou, Zhejiang Province 311121 China
Abstract
Background: 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.
Methods: 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).
Results: 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).
Conclusion: 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.
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BibTeX
@article{zheng2026predictive,
title = {{The predictive value of PD-1 for the response to immune checkpoint inhibitor therapy in patients with bladder cancer without lymph node metastasis and its association with survival outcomes}},
author = {Wei Zheng and Cenchao Yao and Zhida Wang and Chunnan Zhang},
journal = {BMC Cancer},
year = {2026},
month = aug,
doi = {10.1186/s12885-026-16674-z},
url = {https://doi.org/10.1186/s12885-026-16674-z},
note = {CC BY-NC-ND 4.0},
}
RIS
TY - JOUR
TI - The predictive value of PD-1 for the response to immune checkpoint inhibitor therapy in patients with bladder cancer without lymph node metastasis and its association with survival outcomes
AU - Wei Zheng
AU - Cenchao Yao
AU - Zhida Wang
AU - Chunnan Zhang
PY - 2026
DA - 2026/08/07
JO - BMC Cancer
DO - 10.1186/s12885-026-16674-z
UR - https://doi.org/10.1186/s12885-026-16674-z
AB - Background: 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. Methods: 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). Results: 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). Conclusion: 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.
SN - 1471-2407
ER -