Preneoplastic Lesions in Surgical Specimens Do Not Worsen the Prognosis of Patients Who Underwent Surgery for Pancreatic Adenocarcinoma: Post-Hoc Analysis of the PRODIGE 24-CCTG PA 6 Trial

SIMPLE SUMMARY: Pancreatic cancer patients who undergo curative surgery are still likely to recur. We therefore analyzed the data of the 493 patients from the PRODIGE 24-CCTG PA 6 trial, which validated the benefit of adjuvant mFOLFIRINOX regimen over gemcitabine after pancreatic adenocarcinoma resection. We investigated whether the presence of dysplasia (noninvasive intraductal papillary mucinous neoplasm, mucinous cystic neoplasm or pancreatic intraepithelial neoplasia) might decrease in disease-free survival. A preneoplastic lesion was identified in 226 patients (45.8%). In a multivariate analysis, the presence of dysplasia is not an independent predictor of diminished disease-free survival. This finding should be useful for future prospective trials and for surgeons’ decision making, as the pre-existence of a preneoplastic lesion should not preclude a plan for curative surgery. ABSTRACT: Objective: The prognosis of pancreatic cancer after curative surgery is burdened by frequent recurrence. The aim of this study was to evaluate the impact of dysplasia in the surgical specimen on disease-free survival (DFS). Methods: A post-hoc analysis of the phase III PRODIGE 24-CCTG PA 6 trial was performed. From April 2012 to October 2016, 493 patients were included in the primary study. Assessment for dysplasia in the surgical specimens was secondarily performed. Dysplasia was defined based on presence and grade of three most common pre-malignant lesions (intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN) and pancreatic intraepithelial neoplasia (PanIN). The primary endpoint was DFS validated through multivariate analysis. Results: Two hundred twenty-six patients (45.9%) had a preneoplastic lesion. PanIN lesions were found in 193 patients (39.2%), including 100 high-grade lesions (20.6%); 43 patients had IPMN lesions (8.7%), including high-grade lesions in 32 (6.5%). Three MCN were described (0.6%). In bivariate analysis, the presence of dysplasia was not associated with poorer DFS (HR = 0.82, 95% CI [0.66; 1.03]). In multivariate analysis, risk factors for poorer DFS were poorly differentiated/undifferentiated tumor, N1 status, R1 surgical margins and perineural invasion. Conclusions: The presence of dysplasia in the surgical specimen after pancreatic cancer surgery does not worsen DFS.