Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): an international randomised non-inferiority trial

Maarten Korrel, Leia R Jones, Jony van Hilst, Gianpaolo Balzano, Bergthor 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 B Kleive, Arto Kokkola, Daan J Lips, Sanne Lof, Misha D P Luyer, Alberto Manzoni, Ravi Marudanayagam, Matteo de Pastena, Nicolò Pecorelli, John N Primrose, Claudio Ricci, Roberto Salvia, Per Sandström, Frederique L I M Vissers, Ulrich F Wellner, Alessandro Zerbi, Marcel G W Dijkgraaf, Marc G Besselink, Mohammad Abu Hilal, European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS), Adnan Alseidi, Constanza Aquilano, Johanna Arola, Denise Bianchi, Rachel Brown, Daniela Campani, Joanne ChinAleong, Jerome Cros, Lyubomira Dimitrova, Claudio Doglioni, Safi Dokmak, Russell Dorer, Michael Doukas, Jean Michel Fabre, Giovanni Ferrari, Viacheslay Grinevich, Stefano Gobbo, Thilo Hackert, Marius van den Heuvel, Clement Huijsentruijt, Mar Iglesias, Casper Jansen, Igor Khatkov, David Kooby, Marco Lena, Claudio Luchini, Krishna Menon, Patrick Michenet, Quintus Molenaar, Anna Nedkova, Andrea Pietrabissa, Mihaela Raicu, Rushda Rajak, Branislava Rankovic, Aniko Rendek, Benjamin Riviere, Antonio Sa Cunha, Olivier Saint Marc, Patricia Sanchez Velazquez, Donatella Santini, Aldo Scarpa, Mylene Sebagh, Donald Sears, Mihir Shah, Zahir Soonawalla, Paola Spaggiari, Lars Tharun, Tore Tholfsen, Ales Tomazic, Alessandro Vanoli, Caroline Verbeke, Joanne Verheij, Moritz Von Winterfeld, Roeland de Wilde, Vincent Yip, Yoh Zen, Maarten Korrel, Leia R Jones, Jony van Hilst, Gianpaolo Balzano, Bergthor 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 B Kleive, Arto Kokkola, Daan J Lips, Sanne Lof, Misha D P Luyer, Alberto Manzoni, Ravi Marudanayagam, Matteo de Pastena, Nicolò Pecorelli, John N Primrose, Claudio Ricci, Roberto Salvia, Per Sandström, Frederique L I M Vissers, Ulrich F Wellner, Alessandro Zerbi, Marcel G W Dijkgraaf, Marc G Besselink, Mohammad Abu Hilal, European Consortium on Minimally Invasive Pancreatic Surgery (E-MIPS), Adnan Alseidi, Constanza Aquilano, Johanna Arola, Denise Bianchi, Rachel Brown, Daniela Campani, Joanne ChinAleong, Jerome Cros, Lyubomira Dimitrova, Claudio Doglioni, Safi Dokmak, Russell Dorer, Michael Doukas, Jean Michel Fabre, Giovanni Ferrari, Viacheslay Grinevich, Stefano Gobbo, Thilo Hackert, Marius van den Heuvel, Clement Huijsentruijt, Mar Iglesias, Casper Jansen, Igor Khatkov, David Kooby, Marco Lena, Claudio Luchini, Krishna Menon, Patrick Michenet, Quintus Molenaar, Anna Nedkova, Andrea Pietrabissa, Mihaela Raicu, Rushda Rajak, Branislava Rankovic, Aniko Rendek, Benjamin Riviere, Antonio Sa Cunha, Olivier Saint Marc, Patricia Sanchez Velazquez, Donatella Santini, Aldo Scarpa, Mylene Sebagh, Donald Sears, Mihir Shah, Zahir Soonawalla, Paola Spaggiari, Lars Tharun, Tore Tholfsen, Ales Tomazic, Alessandro Vanoli, Caroline Verbeke, Joanne Verheij, Moritz Von Winterfeld, Roeland 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: Between May 8, 2018 and May 7, 2021, 258 patients were randomly assigned to MIDP (131 patients) or ODP (127 patients). Modified intention-to-treat analysis included 114 patients in the MIDP group and 110 patients in the ODP group. An R0 resection occurred in 83 (73%) patients in the MIDP group and in 76 (69%) patients in the ODP group (difference 3.7%, 90% CI -6.2 to 13.6%; pnon-inferiority = 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.

Keywords: Distal pancreatectomy; Minimally invasive surgery; Pancreatic ductal adenocarcinoma.

Conflict of interest statement

Tobias Keck is a member of the advisory board for Olympus, Medtronic, and Dexter. Daan Lips received a proctoring grant by 10.13039/100010477Intuitive Surgical. Marc Besselink and Mohammad Abu Hilal received Investigator Initiated Research grants by Medtronic (DIPLOMA trial), Ethicon (DIPLOMA trial and E-MIPS registry), and Intuitive Surgical (E-MIPS registry) and proctoring grants for Dutch and European training programs in robotic pancreatoduodenectomy by Intuitive Surgical. The other authors have no conflicts of interest.

© 2023 The Authors.

Figures

Fig. 1
Fig. 1
Trialprofile.
Fig. 2
Fig. 2
Overall and disease-free survival after MIDP and ODP in patients with resectable pancreatic cancer according to intention-to-treat. Survival analyses were performed with Kaplan–Meier estimated and log-rank tests. a) Kaplan–Meier curves for overall survival, hazard ratio was 0.99 (95% CI 0.67–1.46, p = 0.94). b) Kaplan–Meier curves for disease-free survival, hazard ratio was 0.97 (95% CI 0.67–1.42, p = 0.88).

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Source: PubMed

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