Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma

Our plain-English summary of Soluble Mesothelin-Related Peptides to Monitor Recurrence After Resection of Pleural Mesothelioma, by B.M. Burt, H.S. Lee, V. Lenge De Rosen, et al (The Annals of Thoracic Surgery, 2017).

The study

• Authors: B.M. Burt, H.S. Lee, V. Lenge De Rosen, M. Hamaji, S.S. Groth, T.M. Wheeler, D.J. Sugarbaker
• Journal: The Annals of Thoracic Surgery
• Published: 2017;104(5):1679-1687
• Cited by: 18 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Background: Most patients undergoing surgical resection of malignant pleural mesothelioma (MPM) will experience recurrence, and radiographic diagnosis of recurrence can be difficult in the postoperative chest. Our objective was to determine the utility of the serum biomarker soluble mesothelin-related peptide (SMRP; or mesothelin) in monitoring of the postoperative MPM patient.

Methods: We retrospectively evaluated a prospectively maintained single institution clinical database. SMRP levels were evaluated preoperatively and postoperatively in patients undergoing surgical resection of MPM.

Results: One hundred two patients underwent pleurectomy/decortication (58%), extrapleural pneumonectomy (20%), chest wall resection (2%), or exploratory thoracotomy (20%) for MPM of 81% epithelial histology. Sixty percent received heated intraoperative chemotherapy and 57% received perioperative systemic chemotherapy. Patients with epithelial histology had substantially greater mean (± SD) preoperative SMRP levels (4.5 ± 7.3 nmol/L) than did patients with biphasic (1.9 ± 2.5 nmol/L) or sarcomatoid (1.2 ± 1.0 nmol/L) histology. Radiologic 3-dimensional tumor volume and tumor mesothelin gene (MSLN) expression correlated with preoperative SMRP. In patients with epithelial histology undergoing complete resection (n = 66), preoperative SMRP (3.4 ± 4.9 nmol/L) dramatically decreased immediately after operation (0.8 ± 0.5 nmol/L), and preoperative SMRP was independently associated with poor disease-free survival. Percentage of change in serial postoperative SMRP values at the best statistical cutoff at 48% revealed high predictive capability of disease recurrence with 90% sensitivity and 93% specificity (area under the curve = 0.96, p < 0.001).

Conclusions: SMRP is a promising serum biomarker for the detection of recurrence after resection of epithelial MPM that may have value in clinical practice and should be studied in a prospective cohort.

Copyright © 2017 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.

In plain English

This study asked whether a blood test for soluble mesothelin-related peptide (SMRP, or mesothelin) can help detect malignant pleural mesothelioma returning after surgery. The authors retrospectively reviewed records of 102 patients operated on at one Texas institution between August 2014 and August 2016. Asbestos exposure was not examined. Before surgery, average SMRP was higher with epithelial tumors (4.5 nmol/L) than with biphasic (1.9) or sarcomatoid (1.2) tumors. In 66 patients with epithelial tumors whose visible tumor was fully removed, average SMRP fell from 3.4 to 0.8 nmol/L within 3 months. In this group, higher preoperative SMRP was independently associated with worse disease-free survival, but not independently with overall survival. Among 47 of these patients with at least two postoperative tests, a rise of 48% or more identified recurrence with 90% sensitivity and 93% specificity. The authors concluded that SMRP is a promising marker for detecting recurrence after surgery for epithelial mesothelioma and should be studied prospectively. They named the retrospective design, short follow-up and irregular test timing 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 review of a prospectively maintained single-institution clinical database (biomarker study)
• Who was studied: 102 patients with malignant pleural mesothelioma who had surgery with curative intent at Baylor College of Medicine, Houston, between August 2014 and August 2016 and had a preoperative SMRP level. Subgroups: 66 with epithelial histology and complete macroscopic resection; 47 of those with at least two postoperative SMRP values; 31 for tumor volume; 10 for gene expression.
• Exposure: Not an asbestos exposure study: no fiber types, products or jobs were reported. The factor studied was the blood level of SMRP, measured before and after surgery with the Mesomark assay.
• Main results:
  • In all 102 patients, mean (plus or minus SD) preoperative SMRP was 4.5 ± 7.3 nmol/L with epithelial histology, 1.9 ± 2.5 nmol/L with biphasic and 1.2 ± 1.0 nmol/L with sarcomatoid histology.
  • Preoperative SMRP did not differ substantially by pathologic stage (I to II, III, IV).
  • In 31 patients with epithelial histology, tumor volume on CT correlated with SMRP. In 10 epithelial tumors, tumor mesothelin gene (MSLN) expression correlated with serum SMRP. No correlation coefficients are given in the text.
  • In 66 patients with epithelial histology and complete resection, mean SMRP fell from 3.4 ± 4.9 nmol/L before surgery to 0.8 ± 0.5 nmol/L within 3 months after surgery. The fall occurred mainly in patients whose preoperative SMRP was 1.0 nmol/L or greater.
  • In the 66-patient cohort, preoperative SMRP was independently associated with disease-free survival (multivariable hazard ratio 1.06 per nmol/L, 95% CI 1.00 to 1.11, p 0.04). It was not independently associated with overall survival (hazard ratio 1.05, 95% CI 0.99 to 1.10, p 0.089).
  • In 47 patients with at least two postoperative SMRP values (19 with recurrence, 28 without), percentage change in SMRP had an area under the curve of 0.96 for recurrence. At the best cutoff, a rise of 48%, sensitivity was 90% and specificity 93%.
• The authors' conclusion: The authors concluded that SMRP is a promising serum biomarker for detecting recurrence after resection of epithelial malignant pleural mesothelioma that may have value in clinical practice. They suggested that a postoperative rise of about 50% suggests recurrence or impending recurrence, and called for a prospective study.
• Limitations the authors state:
  • The retrospective design introduces selection and information biases.
  • The follow-up period was relatively short.
  • Postoperative SMRP was not measured on a standardized schedule, which may have introduced unrecognized biases.
  • The gene expression analysis included only 10 patients.

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: Soluble Mesothelin-Related Peptides (SMRP), Pleural Mesothelioma, Surgical Resection, Biomarker, Mesothelin, Pleurectomy/Decortication (P/D), Extrapleural Pneumonectomy (EPP), Thoracotomy.

Related studies

• Association of MiR-126 with soluble mesothelin-related peptides, a marker for malignant mesothelioma — L. Santarelli, E. Strafella, et al. (2011)
• Soluble mesothelin-related peptide level elevation in mesothelioma serum and pleural effusions — H.I. Pass, A. Wali, et al. (2008)
• Evaluation of soluble mesothelin-related peptide as a diagnostic marker of malignant pleural mesothelioma effusions: its contribution to cytology — P.A. Canessa, M.C. Franceschini, et al. (2013)
• Two novel polymorphisms in 5' flanking region of the mesothelin gene are associated with soluble mesothelin-related peptide (SMRP) levels — A. Cristaudo, R. Foddis, et al. (2011)
• Mesothelin promoter variants are associated with increased soluble mesothelin-related peptide levels in asbestos-exposed individuals — C. De Santi, P. Pucci, et al. (2017)
• Evaluation of soluble mesothelin-related peptides and MSLN genetic variability in asbestos-related diseases — K. Goricar, V. Kovac, et al. (2020)

Browse more research in The Annals of Thoracic Surgery, or return to medical research.