Minimally invasive pancreatoduodenectomy (MIPD) might accelerate postoperative recovery in patients with primary resectable neoplasm compared with open pancreatoduodenectomy (OPD), although the safety of MIPD remains debated. We aimed to assess whether MIPD is noninferior to OPD for overall complications and superior for time to functional recovery (TTFR).

We conducted an international, multicenter, patient-blinded randomized noninferiority trial in patients undergoing pancreatoduodenectomy for primary resectable pancreatic and periampullary neoplasm from high-volume centers. Patients were randomly assigned in a 2:1 ratio to undergo robot-assisted or laparoscopic MIPD versus OPD and were blinded to the procedure until postoperative day 5. The primary end point was overall complications within 90 days of surgery, as measured using the Comprehensive Complication Index (range 0–100, with higher scores indicating more severe complications). Noninferiority was tested using a margin of −7.5 points (one-sided 97.5% confidence interval [CI]; P<0.025 for noninferiority). The main secondary end point was TTFR, tested for superiority. Analyses were reported by the intention-to-treat principle.

Overall, 288 patients were randomly assigned (190 MIPD [170 robot-assisted, 20 laparoscopic] and 98 OPD) in 14 centers. The mean Comprehensive Complication Index was 33.4±27.5 in the MIPD group versus 35.3±25.5 in the OPD group (mean difference, −1.9; 95% CI, −8.5 to 4.7; P=0.002 for nonferiority). In the MIPD group, the median TTFR was 7 days (95% CI, 6 to 8) versus 8 days (95% CI, 7 to 11) in the OPD group. The MIPD conversion rate to open surgery was 8.4%. Rates of postoperative pancreatic fistula were 22.6% versus 35.7% (relative risk 0.63; 95% CI, 0.43 to 0.91) and were 12.6% versus 22.7% (relative risk 0.57; 95% CI, 0.32 to 0.98) for surgical site infection after MIPD and OPD, respectively. Death by 90 days occurred in 4.7% of patients after MIPD versus 2.0% after OPD (relative risk 2.40; 95% CI, 0.51 to 11.30).

In patients with resectable pancreatic and periampullary neoplasm, MIPD was noninferior to OPD for 90-day overall complications (Funded by Intuitive Surgical and Fondazione Poliambulanza Istituto Ospedaliero; International Standard Randomised Controlled Trial Number Registry, ISRCTN27483786.)