PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma

Our plain-English summary of PD-L1 expression associated with worse survival outcome in malignant pleural mesothelioma, by B.H. Nguyen, R. Montgomery, M. Fadia, et al (Asia-Pacific Journal of Clinical Oncology, 2018).

The study

• Authors: B.H. Nguyen, R. Montgomery, M. Fadia, J. Wang, S. Ali
• Journal: Asia-Pacific Journal of Clinical Oncology
• Published: 2018;14(1):69-73
• Cited by: 37 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Aim: There is currently a need to identify prognostic biomarkers to assist in a risk adopted approach in treatment of malignant pleural mesothelioma (MPM). Expression of programmed death ligand 1 (PD-L1) has been studied as a prognostic biomarker in a number of tumors given its central role in antitumoral immune response evasion. Four previously published analyses found PD-L1 positivity to be an adverse survival prognostic factor in MPM. This study aims to further investigate the relationship between PD-L1 expression in mesothelioma tissues and survival outcome.

Methods: Clinical data of MPM patients from a single institution between 2006 and 2016 were reviewed. Patient's archived tissues were stained with PD-L1 (Clone Ventana SP263). PD-L1 positivity was defined as > 1% membranous staining regardless of intensity.

Results: Data from fifty eight patients were analyzed. Median age was 73, majority was male (49, 84%) and had ECOG between 0 and 2 (46, 79%). Most common histopathological subtype was epithelioid (42, 72%), 9 (16%) biphasic subtype and 7 (12%) sarcomatoid. Thirty one patients (53%) received best supportive care and twenty seven patients (47%) received chemotherapy or combination treatment. Forty-two patients had positive PD-L1 expression (72.4%). The median survival time for PD-L1 negative group is 15.5 months and 6 months for the positive group. Positive PD-L1 expression is independently correlated with worse prognosis (HR = 2.02; 95% CI, 1.005-4.057; P-value = 0.0484).

Conclusions: Our analysis found a higher percentage of MPM patients with positive PD-L1 (> 1%) compared to other studies. Highly positive PD-L1 expression was associated with statistically significantly lower median survival time.

© 2017 John Wiley & Sons Australia, Ltd.

In plain English

This was a retrospective study from Canberra, Australia, of 58 consecutive patients diagnosed with malignant pleural mesothelioma on pleural biopsy between January 2006 and December 2016. It did not look at asbestos exposure. The authors stained the patients' stored tumor tissue for a protein called PD-L1 and counted a tumor as positive if more than 1% of tumor cells showed staining on the cell membrane. Forty-two patients (72%) were PD-L1 positive and 16 were negative. Median survival was 6 months in the positive group and 15.5 months in the negative group. A simple comparison of the two survival curves was not statistically significant (P = 0.0893). After adjusting for sex, ECOG level, tumor subtype, treatment and age, PD-L1 positivity was linked to worse survival (hazard ratio 2.02; 95% CI 1.005 to 4.057; P = 0.0484). Sarcomatoid subtype and ECOG level 3 were also linked to worse survival. The authors concluded that positive PD-L1 was associated with significantly lower median survival time, and they called for larger, prospective studies. They named the small sample and the retrospective design as limitations.

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 tumor biopsies (immunohistochemistry) linked to survival records
• Who was studied: 58 consecutive patients with malignant pleural mesothelioma diagnosed on pleural biopsy at ACT Pathology / The Canberra Hospital, Australia, January 2006 to December 2016. Ten patients with incomplete records or lost to follow-up were excluded. Median age was 73, 49 (84%) were male, and the subtypes were 42 epithelioid, 7 sarcomatoid and 9 biphasic.
• Exposure: Not asbestos. The factor studied was PD-L1 protein expression in tumor tissue, tested with the VENTANA SP263 antibody. A tumor was counted as positive when more than 1% of tumor cells showed membrane staining, partial or complete, regardless of intensity. Asbestos exposure was not assessed.
• Main results:
  • Of the 58 patients, 42 (72%) were PD-L1 positive and 16 (28%) were PD-L1 negative.
  • Median survival was 15.5 months in the PD-L1 negative group and 6 months in the PD-L1 positive group. The unadjusted log-rank comparison was not statistically significant (P = 0.0893).
  • In the multivariate Cox model, adjusted for gender, ECOG level, histology subtype, treatment and age, positive PD-L1 expression was associated with worse prognosis: HR 2.02; 95% CI 1.005 to 4.057; P = 0.0484.
  • Worse survival was also associated with sarcomatoid subtype (HR 4.47; 95% CI 1.218 to 16.165; P = 0.0232) and with ECOG level 3 (HR 3.72; 95% CI 1.319 to 10.487; P = 0.013). Gender and treatment type showed no significant association with survival.
  • All 7 sarcomatoid tumors were PD-L1 positive. The article also reports 6 of 9 biphasic and 13 of 42 epithelioid tumors as positive. The link between PD-L1 positivity and subtype was not statistically significant (Fisher's exact test P = 0.2763).
• The authors' conclusion: The authors concluded that their small analysis found a higher percentage of PD-L1 positive patients than other studies, and that positive PD-L1 expression was associated with significantly lower median survival time. They said PD-L1 testing as a prognostic and predictive marker should be investigated in larger, prospective trials.
• Limitations the authors state:
  • The small number of patients limits the statistical analysis.
  • Because the study was retrospective, variable record-keeping and documentation quality may affect data integrity.
  • 53% of patients did not receive chemotherapy, a higher share than in other datasets. This was possibly because patients from before pemetrexed subsidy were included, and it may skew the survival results.
  • The authors could not tell whether PD-L1 is an independent prognostic marker or a stand-in for the more aggressive sarcomatoid subtype. They attributed the non-significant subtype correlation possibly to the limited sample size.
  • TIL levels were not characterized, so the authors could not comment on the association of TIL level with survival.
  • Spatial and temporal variation in PD-L1 staining, and the lack of an agreed positivity cut-off, limit how reproducible PD-L1 is as a biomarker.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer, Mesothelioma.

Medical terms in this study, explained in our Lexicon: PD-L1, Pleural Mesothelioma, Biomarker, Mesothelioma, Epithelioid, Biphasic Mesothelioma, Sarcomatoid, Chemotherapy.

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• Shorter Survival in Malignant Pleural Mesothelioma Patients With High PD-L1 Expression Associated With Sarcomatoid or Biphasic Histology Subtype: A Series of 214 Cases From the Bio-MAPS Cohort — S. Brosseau, C. Danel, et al. (2019)
• Expression of ALCAM (CD166) and PD-L1 (CD274) independently predicts shorter survival in malignant pleural mesothelioma — S. Inaguma, J. Lasota, et al. (2018)
• Immunohistochemical evaluation of two antibodies against PD-L1 and prognostic significance of PD-L1 expression in epithelioid peritoneal malignant mesothelioma: A RENAPE study — S. Valmary-Degano, P. Colpart, et al. (2017)
• Programmed cell death 1 ligand 1 (PD-L1) expression is associated with poor prognosis of malignant pleural mesothelioma patients with good performance status — E. Rrapaj, L. Giacometti, et al. (2021)
• Malignant pleural mesothelioma: clinical experience and prognostic value of derived neutrophil-to-lymphocyte ratio and PD-L1 expression — L. Gutierrez-Sainz, P. Cruz, et al. (2021)

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