PD-L1 expression as a prognostic factor for postoperative outcomes in pleural mesothelioma

Our plain-English summary of PD-L1 expression as a prognostic factor for postoperative outcomes in pleural mesothelioma, by M. Kanayama, T. Manabe, K. Yoshimatsu, et al (Translational Lung Cancer Research, 2025).

The study

• Authors: M. Kanayama, T. Manabe, K. Yoshimatsu, Y. Nemoto, H. Matsumiya, M. Mori, M. Takenaka, K. Kuroda, F. Tanaka
• Journal: Translational Lung Cancer Research
• Published: 2025;14(9):3913-3923
• Read it: PubMed · Publisher · Free full text

Abstract

Background: Pleural mesothelioma (PM) is an uncommon malignancy with a poor prognosis, even after surgical resection. Programmed death-ligand 1 (PD-L1) expression is a potential prognostic biomarker in various cancers, yet its role in PM patients undergoing pleurectomy/decortication (P/D) is unclear. This study aimed to evaluate the prognostic significance of PD-L1 expression in patients with PM who underwent P/D.

Methods: This retrospective study included patients with PM who underwent P/D from 2012 to 2022. PD-L1 expression in tumor cells was evaluated by immunohistochemistry, categorizing patients by tumor proportion score (TPS): 0%, 1-49%, and ≥50%. Survival outcomes were assessed using Kaplan-Meier curves and Cox proportional hazards regression models.

Results: A total of 58 patients were enrolled in the study. The median overall survival (OS) was 77.0 months for TPS 0%, 41.0 months for TPS 1-49%, and 25.3 months for TPS ≥50%. The corresponding relapse-free survival (RFS) was 34.3, 13.2, and 6.7 months, respectively. Lower PD-L1 expression was significantly associated with improved outcomes (OS: P=0.041, RFS: P=0.002). In multivariable analysis, PD-L1 TPS 0% (vs. ≥1%) emerged as an independent prognostic factor for RFS (hazard ratio, 0.37; 95% confidence interval: 0.18-0.76; P=0.007), but not OS.

Conclusions: Our findings suggest that PD-L1 expression levels in tumor cells may influence postoperative prognosis and relapse risk in patients with PM undergoing P/D. Lower PD-L1 expression correlates with improved survival outcomes, positioning PD-L1 as a potential biomarker to inform therapeutic strategies in this population. Further studies are warranted to explore the implications of PD-L1 in treatment decisions.

Copyright © 2025 AME Publishing Company. All rights reserved.

In plain English

This retrospective study from one surgical department in Kitakyushu, Japan, covered 58 pleural mesothelioma patients who had pleurectomy/decortication surgery in 2012–2022; asbestos exposure was not examined. The authors measured a protein called PD-L1 on tumor cells in removed tissue and grouped patients by the share of cells showing it: 0%, 1–49%, or 50% or more. Measured from surgery, median overall survival was 77.0 months (95% confidence interval 20.7–133.2), 41.0 months (22.7–59.3) and 25.3 months (7.1–42.9) in those groups. Median relapse-free survival, the time to relapse or death, was 34.3 (22.8–45.8), 13.2 (7.4–19.0) and 6.7 months (3.6–9.8). Lower PD-L1 was significantly associated with better outcomes. After adjusting for other factors, 0% PD-L1 (versus 1% or more) was linked to a lower hazard of relapse or death (hazard ratio 0.37; 95% confidence interval 0.18–0.76). This was not found for overall survival. No significant association was found in non-epithelioid tumors. The authors concluded that PD-L1 expression is a prognostic factor after this surgery. Limitations they noted included a small single-center sample and a high share of sarcomatoid cases.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Retrospective single-institution study of surgical patients (survival analysis using Kaplan-Meier curves and Cox regression)
• Who was studied: 58 patients with pleural mesothelioma who underwent pleurectomy/decortication at the University of Occupational and Environmental Health, Japan, from January 2012 to December 2022. Of 67 operated patients, 5 salvage-surgery cases and 4 cases where PD-L1 could not be evaluated were excluded. 89.7% were male and the median age was 69. Tumor types were 42 epithelioid, 6 biphasic and 10 sarcomatoid.
• Exposure: No asbestos exposure data were collected or analyzed. The factor studied was PD-L1 expression in tumor cells, measured by immunohistochemistry on surgical specimens as the tumor proportion score. Patients were grouped as 0%, 1–49% and 50% or more. 1% or more was defined as PD-L1 positive and 50% or more as high expression.
• Main results:
  • Distribution among the 58 patients: 36.2% (21) had PD-L1 0%, 44.8% (26) had 1–49%, and 19.0% (11) had 50% or more.
  • All patients: median overall survival, measured from surgery to death from any cause, was 77.0 months (95% CI 20.7–133.2) for TPS 0%, 41.0 months (95% CI 22.7–59.3) for TPS 1–49%, and 25.3 months (95% CI 7.1–42.9) for TPS 50% or more.
  • All patients: median relapse-free survival, measured from surgery to relapse or death, was 34.3 months (95% CI 22.8–45.8) for TPS 0%, 13.2 months (95% CI 7.4–19.0) for TPS 1–49%, and 6.7 months (95% CI 3.6–9.8) for TPS 50% or more.
  • Across the three groups of all patients, lower PD-L1 expression was significantly associated with better outcomes (overall survival P=0.041; relapse-free survival P=0.002).
  • All patients, multivariable analysis (model 1): PD-L1 TPS 0% versus 1% or more was an independent prognostic factor for relapse-free survival, an endpoint counting relapse or death (HR 0.37; 95% CI 0.18–0.76; P=0.007).
  • All patients, multivariable analysis (model 2): PD-L1 under 50% versus 50% or more was not an independent prognostic factor for overall survival (HR 0.61; 95% CI 0.21–1.75; P=0.36) or for relapse-free survival (HR 0.46; 95% CI 0.20–1.04; P=0.06).
  • Epithelioid patients only: PD-L1 TPS 0% versus 1% or more was an independent prognostic factor for relapse-free survival (HR 0.35; 95% CI 0.15–0.81; P=0.01).
  • Non-epithelioid patients only: no significant association was found between PD-L1 expression and overall survival (P=0.11) or relapse-free survival (P=0.75).
  • Among the 43 patients who relapsed, those with TPS 1% or more had significantly better survival after relapse than those with TPS 0%: 18.4 months (95% CI 9.7–27.1) versus 5.0 months (95% CI 1.4–8.6), P=0.006.
  • Among relapsed patients, those treated with immune checkpoint inhibitors showed a trend toward better survival that was not statistically significant (18.4 versus 7.7 months, P=0.12).
• The authors' conclusion: The authors concluded that tumor-cell PD-L1 expression is a prognostic factor in pleural mesothelioma patients undergoing pleurectomy/decortication, with lower expression associated with better outcomes. They suggested PD-L1 could serve as a biomarker to help guide treatment decisions.
• Limitations the authors state:
  • The study was done at a single institution with a limited sample size, which may have introduced selection bias.
  • PD-L1 was measured on postoperative specimens, which may not fully reflect preoperative PD-L1 status.
  • The share of sarcomatoid mesothelioma (17%) was higher than usually reported in surgical series. This may have influenced the findings and could limit generalizability.
  • PD-L1 expression can vary within a tumor and between testing platforms, which may lead to misclassification and affect reproducibility.
  • Other emerging prognostic factors, such as immune-related factors, tumor-infiltrating lymphocytes and tumor mutational burden, were not included.

Topics

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, Prognosis, Surgical Resection, Biomarker, Pleurectomy/Decortication (P/D), Immunohistochemistry, Kaplan-Meier Curve.

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