Surgical Complications in Patients with (borderline) Resectable Pancreatic Cancer after Neoadjuvant Therapy in the PREOPANC-2 Randomized Controlled Trial

Abstract

Objective: To compare the incidence of major surgical complications between patients with (borderline) resectable pancreatic cancer treated with neoadjuvant FOLFIRINOX versus neoadjuvant gemcitabine-based chemoradiotherapy.

Summary of background data: There are ongoing concerns regarding the possible adverse impact of neoadjuvant treatment on postoperative complication rates following pancreatectomy.

Methods: This study was a predefined analysis within the investigator-initiated nationwide randomized controlled PREOPANC-2 trial. Patients with (borderline) resectable pancreatic cancer were randomized to receive neoadjuvant FOLFIRINOX (FFX group) or neoadjuvant gemcitabine-based chemoradiotherapy (CRT group), both followed by surgery, and adjuvant gemcitabine only in the CRT group. Surgical complications including postoperative pancreatic fistula, postpancreatectomy hemorrhage, bile leakage, postoperative interventions, and 90-day mortality were compared, with major complications defined as Clavien-Dindo grade ≥3.

Results: Between June 5, 2018, and January 28, 2021, in total 375 patients were randomized, of whom 280 (74.7%) underwent pancreatic resection. A pancreatoduodenectomy was performed in 238 patients (85.0%), left pancreatectomy in 41 patients (14.6%), and total pancreatectomy in one patient (0.4%). The incidence of major surgical complications was similar between the FFX and CRT groups (26.8% versus 27.5%, P=0.884). No differences were observed in the risk of postoperative pancreatic fistula grade B/C (9.9% versus 4.4%, P=0.076), postpancreatectomy hemorrhage grade B/C (7.7% versus 3.6%, P=0.137), bile leakage grade B/C (2.5% versus 2.5%, P>0.999), and postoperative interventions (26.1% versus 26.8%, P=0.886). Surgical reoperation was performed in nine patients (6.3%) in the FFX group and eight patients (5.8%) in the CRT group (P=0.850). The postoperative 90-day mortality was 1.4% in the FFX group (2/142 patients) and 2.9% in the CRT group (4/138 patients) (P=0.442).

Conclusions: In the PREOPANC-2 randomized trial, the risk of major surgical complications after pancreatic resection following neoadjuvant FOLFIRINOX or neoadjuvant gemcitabine-based chemoradiotherapy was similar with an overall low 90-day mortality.

Keywords: PDAC; PREOPANC-2; RCT; investigator-initiated; nationwide; surgical complications.