Conversion Surgery Following Multidisciplinary Therapy in Unresectable Pancreatic Ductal Adenocarcinoma: Impact on Survival

Patients diagnosed with pancreatic ductal adenocarcinoma that is initially deemed unresectable face a very poor prognosis. Conversion surgery, performed after tumor shrinkage or favorable response to therapy, has emerged as a potential intervention to improve survival. This study examines the outcomes and prognostic factors associated with this approach. We retrospectively analyzed cases of pancreatic ductal adenocarcinoma referred for possible surgery at our institution between January 2006 and December 2019. Conversion surgery was reserved for patients with unresectable tumors who were considered capable of achieving complete (R0) resection. Survival outcomes and factors affecting overall survival were evaluated in patients undergoing surgery after initial systemic therapy.

The study included 638 patients with advanced disease. Among them, 180 were initially resectable, 60 were borderline resectable, 252 were locally advanced and unresectable, and 146 had distant metastases. Conversion surgery was ultimately performed in 20 of the 398 patients with unresectable disease (5.1%). The median interval from the start of therapy to surgery was 15.5 months. Treatment responses assessed by RECIST showed one complete response, 13 partial responses, five stable disease cases, and one progression. Pathological evaluation confirmed tumor downstaging in all operated patients. Tumor regression assessed by the Evans system revealed grade I in four patients, grade IIb in seven, grade III in seven, and grade IV in two. Median overall survival calculated from initial treatment was 73.7 months for patients who underwent conversion surgery, compared with 32.7 months for initially resectable, 22.7 months for borderline resectable, 15.7 months for locally advanced unresectable, and 8.8 months for metastatic patients. Multivariate analysis identified receipt of chemoradiotherapy and achieving a partial or complete response by RECIST as significant predictors of improved survival (p = 0.004 and 0.03, respectively). In patients with initially unresectable pancreatic ductal adenocarcinoma, conversion surgery following multimodal therapy, including chemoradiotherapy, can offer substantial survival benefits. Early identification of candidates and coordinated multidisciplinary care are critical to maximize the clinical impact of this approach.