Abstract
Introduction: Up to 30% of patients who undergo pancreatic ductal adenocarcinoma (PDAC) resection face mortality within one year of surgery. We have previously demonstrated that a triple biomarker panel comprising S100A4, Ca-125 and mesothelin predicts median overall survival (mOS) after resection. We aimed to evaluate the association between this triple biomarker panel and transcriptomic PDAC subtypes, clinical PDAC phenotypes, and level of survival benefit received from a neoadjuvant treatment strategy. Method: Patients who underwent resection for resectable and borderline resectable PDAC were included for analysis. PDAC tumours for all patients were immunohistochemically evaluated for expression of S100A4, Ca-125 and mesothelin. Data regarding Bailey transcriptomic classification (progenitor, ADEX, immunogenic or squamous) was obtained from a subset of these patients whose tumour was included in the International Cancer Genomic Consortium (ICGC). Result: 226 patients from the ICGC cohort and 252 patients from a single institution were included for analysis. Triple negative biomarker status was associated with non-squamous PDAC subtypes (OR 5.804, p=0.020). Triple positive biomarker status was characterized by a higher risk of distant disease recurrence compared with triple negative disease (HR 2.136, p=0.002). A neoadjuvant treatment approach was associated with longer mOS compared with upfront surgery in triple biomarker positive patients with resectable and borderline resectable PDAC (29.5 vs 13.7 mths, p=0.021). On the other hand, a neoadjuvant treatment approach was associated with shorter mOS compared with upfront surgery in triple biomarker negative patients with resectable PDAC (22.2 vs. 33.3 mths, p=0.038). Conclusion: Patients with triple positive disease, with a higher risk of distant metastatic recurrence, achieve longer overall survival with a neoadjuvant approach compared with upfront surgery. On the other hand, patients with triple negative disease are likely to have non-squamous subtype PDAC, and achieve longer overall survival with an upfront surgical resection compared with a neoadjuvant treatment approach.
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