Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial
Maarten Korrel, L. Jones, Jony van Hilst, Gianpaolo Balzano, Bergþór Björnsson, Ugo Boggi, Svein Olav Bratlie, Olivier R. Busch, Giovanni Butturini, Giovanni Capretti, Riccardo Casadei, Bjørn Edwin, Anouk M.L.H. Emmen, Alessandro Esposito, Massimo Falconi, Bas Groot Koerkamp, Tobias Keck, Ruben H.J. de Kleine, Dyre Kleive, Arto Kokkola, Daan J. Lips, Sanne Lof, Misha Luyer, Alberto Manzoni, Ravi Marudanayagam, Matteo De Pastena, Nicolò Pecorelli, John N. Primrose, Claudio Ricci, Roberto Salvia, Per Sandström, Frederique L. Vissers, Ulrich F. Wellner, Alessandro Zerbi, Marcel G. W. Dijkgraaf, Marc G. Besselink, Mohammad Abu Hilal, Adnan Alseidi, Constanza Aquilano, Johanna Arola, Denise Bianchi, Rachel M. Brown, Daniela Campani, Joanne Chin‐Aleong, Jérôme Cros, Lyubomira Dimitrova, Claudio Doglioni, Safi Dokmak, Russell Dorer, Michael Doukas, J Fabré, Giovanni Ferrari, В. Н. Гриневич, Stefano Gobbo, Thilo Hackert, Marius van den Heuvel, Clement Huijsentruijt, Mar Iglesias, Casper Jansen, Igor Khatkov, David A. Kooby, Marco Schiavo Lena, Claudio Luchini, Krishna Menon, Patrick Michenet, Q. Molenaar, Anna Nedkova, Andrea Pietrabissa, Mihaela Raicu, Rushda Rajak, Branislava Ranković, Aniko Rendek, Benjamin Rivière, António Sá Cunha, Olivier Saint Marc, Patricia Sánchez‐Velázquez, Donatella Santini, Aldo Scarpa, Mylène Sebagh, Donald L. Sears, Mihir M. Shah, Zahir Soonawalla, Paola Spaggiari, Lars Tharun, Tore Tholfsen, Aleš Tomažič, Alessandro Vanoli, Caroline S. Verbeke, Joanne Verheij, Moritz von Winterfeld, Roeland F. de Wilde, Vincent Yip, Yoh Zen
Abstract
Background: The oncological safety of minimally invasive surgery has been questioned for several abdominal cancers. Concerns also exist regarding the use of minimally invasive distal pancreatectomy (MIDP) in patients with resectable pancreatic cancer as randomised trials are lacking. Methods: In this international randomised non-inferiority trial, we recruited adults with resectable pancreatic cancer from 35 centres in 12 countries. Patients were randomly assigned to either MIDP (laparoscopic or robotic) or open distal pancreatectomy (ODP). Both patients and pathologists were blinded to the assigned approach. Primary endpoint was radical resection (R0, ≥1 mm free margin) in patients who had ultimately undergone resection. Analyses for the primary endpoint were by modified intention-to-treat, excluding patients with missing data on primary endpoint. The pre-defined non-inferiority margin of -7% was compared with the lower limit of the two-sided 90% confidence interval (CI) of absolute difference in the primary endpoint. This trial is registered with the ISRCTN registry (ISRCTN44897265). Findings: = 0.039). Median lymph node yield was comparable (22.0 [16.0-30.0] vs 23.0 [14.0-32.0] nodes, p = 0.86), as was the rate of intraperitoneal recurrence (41% vs 38%, p = 0.45). Median follow-up was 23.5 (interquartile range 17.0-30.0) months. Other postoperative outcomes were comparable, including median time to functional recovery (5 [95% CI 4.5-5.5] vs 5 [95% CI 4.7-5.3] days; p = 0.22) and overall survival (HR 0.99, 95% CI 0.67-1.46, p = 0.94). Serious adverse events were reported in 23 (18%) of 131 patients in the MIDP group vs 28 (22%) of 127 patients in the ODP group. Interpretation: This trial provides evidence on the non-inferiority of MIDP compared to ODP regarding radical resection rates in patients with resectable pancreatic cancer. The present findings support the applicability of minimally invasive surgery in patients with resectable left-sided pancreatic cancer. Funding: Medtronic Covidien AG, Johnson & Johnson Medical Limited, Dutch Gastroenterology Society.