Juuso Paajanen, MD, PhD
Juuso Paajanen*, Ahmed Sadek, William G. Richards, Emanuele Mazzola, Yue Xie, Kristina Sidopoulos, John Kuckelman, Ritu R.Gill, Raphael Bueno
Background: Tumor recurrence remains the main barrier to survival after surgery for pleural mesothelioma (PM). We evaluated the utility of previously established blood-based biomarkers, soluble mesothelin-related protein (SMRP) and cancer antigen 125 (CA-125), for disease monitoring following pleurectomy decortication (PD).
Methods: Patients who achieved complete macroscopic resection after PD with available preoperative SMRP levels were included. Biomarker levels were determined within 60 days of three timepoints: pre-operation, post-operation, and recurrence. Average follow-up surveillance levels were calculated for patients without recurrence. SMRP over 1.5 nmol/L and CA-125 levels over 46 U/mL were categorized as “positive”.
Results: Of 356 available patients, 276 (78%) had recurrence by end of follow-up. Higher preoperative rates of positive SMRP levels were associated with epithelioid histology (P=0.002) and higher TNM stage (P=0.024). Radiographcially measured tumor volume correlated positively with preoperative SMRP levels (rho 0.303, P<0.001). Pre-operative CA-125 levels were not significantly associated with clinical covariates. Positive pre-operative CA-125 (P=0.032) was associated with shorter survival. Positive surveillance SMRP was associated with pleural recurrence (P=0.018), whereas positive CA-125 was related to abdominal recurrence (P=0.002). Among patients with pre-operation, post-operation, and recurrence timepoints available, SMRP levels (N=94) decreased by an average 1.85 nmol/L (P<0.001) post-operatively and increased at the time of recurrence by an average of 0.76 nmol/L (P<0.001). CA-125 levels (N=64) similarly decreased after surgery by an average 32.07 U/mL (P=0.036), but the average change between post-operative and recurrence levels was nonsignificant (29.74 U/mL, P=0.865).
SMRP and CA-125 levels closely follow the radiographic presence of the disease. Longitudinal changes in levels of SMRP and CA-125 corresponded with respective thoracic and abdominal sites of recurrence. SMRP surveillance could aid the detection of otherwise radiologically subtle local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences. Prospective validation of these results is warranted.
Post-operative surveillance in pleural mesothelioma is currently based on radiological imaging, which is nonspecific secondary to postoperative changes following pleurectomy and the unique morphology of the disease. The addition of blood-based biomarkers could act as an adjunct to radiology, leading to earlier and more accurate diagnosis of tumor recurrence. Previously, several biomarkers have been studied for mesothelioma monitoring, but none have been accepted into wide clinal use. We have shown that the serum levels of soluble mesothelin-related protein (SMRP) change significantly in relation to tumor burden. This is not the case for cancer antigen 125 (CA-125). Additionally, higher baseline SMRP levels suggested epithelioid histology with larger tumor volume and advanced TNM stage. Finally, we found that SMRP elevates in relation to thoracic recurrence, while CA-125 is increased with abdominal recurrence. For these reasons, it could be beneficial to use both markers in post-operative settings for PM surveillance.