Background: As many as 25% patients with a histological diagnosis of NSP at a thoracoscopic biopsy are eventually diagnosed with a malignancy, mostly mesothelioma, over the following months.

Aim: to evaluate the value of pleural effusion levels of soluble mesothelin-related peptides (PE-SMRP) as a diagnostic tool in patients with histological diagnosis of NSP.

Methods: All patients with an exudative pleural effusion and a histological diagnosis of NSP at thoracoscopic biopsies performed between Jenuary 2008 and December 2020 were followed for 18 months. A predefined cut-off level of 20 nM PE-SMRP, based on published data, was used to distinguish high- from low- PE-SMRP patients. A binary logistic regression was used to measure the relative risk of a later diagnosis of cancer.

Results: Of the 185 patients with a diagnosis of NSP, 17 (9.2%) were diagnosed with cancer during follow-up (mean 6.38 months). A malignancy was diagnosed in 9 of the 15 high-PE-SMRP patients (60%), and in 8 of the 170 low-PE-SMRP patients (4.7%) (p<0.0001). High-PE-SMRP patients had a higher risk of being diagnosed with mesothelioma at follow-up (OR 31.2, 95% IC 8.5-114.7) (table 1).

Mesothelin Level(nM) Mesothelioma Occurence DOR 95% CI P-value


N0 (%)


N0 (%)

?20 164 (95.9%) 6 (42.9%) 1.0 - <0.001
>20 7 (4.1%) 8 (57.1%) 31.2 8.5-114.7 <0.001

Each nM increase in PE-SMRP increased the risk of a final diagnosis of mesothelioma by 1.07-fold (p<0.001).

Conclusions:Patients with high levels of PE-SMRP are at increased risk of cancer after an initial histological diagnosis of NSP and might benefit from a closer follow-up.