Background

Current monitoring of pleural mesothelioma (PM) consists of serial CT scans, interpreted using modified RECIST criteria. These criteria are imperfect, however. A blood-based biomarker could reduce radiation exposure, allow more frequent testing & provide more accurate & responsive disease monitoring.

Objectives

To evaluate the relationship between changes in serial serum mesothelin (SM) &

1)      radiological disease status

2)      survival

Methods

PM patients were enrolled in a multi-centre prospective longitudinal cohort study between 28/2/2017 & 22/11/2022. Logistic regression & cox survival analysis, adjusted for sex, age, histology, performance status, eGFR & treatment, were used to assess the relationship between serial SM, & progression & survival.

Results

209 participants were eligible. A rise in SM was associated with disease progression (adj OR 1.51, 95% CI 1.01-1.95,p<0.01), whether initial SM was ?2mmol/L (adj OR 1.60, 95% CI 1.10-2.32,p=0.02) or <2mmol/L (adj OR 1.62, 95% CI 1.02-2.57,p=0.04). In time-to-event analysis, a rise in SM doubled the likelihood of disease progression (adj HR 2.20, 95% CI 1.04-4.66,p=0.04).

In people who received chemotherapy, a SM fall was associated with disease response (adj OR 1.40, 95% CI 1.03-1.92,p=0.03). A rise in SM predicted progression in those receiving supportive care (adj OR 1.51, 95% CI 1.17-1.93,p=0.001).

Initial SM?2 was associated with higher mortality (adj HR 1.98, 95% CI 1.13-3.47, p=0.02).

Conclusion:

This study, the largest to date, shows serial SM reliably predicts PM disease response, progression & survival across all patient groups. SM monitoring has several benefits over CT scanning & offers a valid biomarker for surveillance.