For patients with fully resectable pancreatic cancer, a minimally invasive surgical approach—laparoscopic or robotic—was shown to be comparable to open distal pancreatectomy in the multicenter randomized phase III DIPLOMA trial. These results were presented at the 2023 ASCO Annual Meeting and at a press briefing prior to the meeting.1
DIPLOMA is the first randomized, patient-blinded study to compare outcomes between open and minimally invasive surgery for patients with early-stage pancreatic cancer involving the body or tail of the pancreas. The noninferiority trial demonstrated comparability in multiple outcomes, including R0 resection, lymph node retrieval, functional recovery, and survival.
“Surgery has made significant advances in the past 2 decades. One of the most important is the introduction of minimally invasive surgery. For pancreatic cancer, we have proven for the first time that minimally invasive distal pancreatectomy is as good as open surgery,” said Mohammad Abu Hilal, MD, PhD, Surgical Director at the Instituto Ospedaliero Fondazione Poliambulanza in Brescia, Italy.
Mohammad Abu Hilal, MD, PhD
The primary endpoint was R0 resection, indicating complete removal of the tumor and at least 1 mm of surrounding tissue. This was achieved by 73% of the minimally invasive group and 69% of the open surgery group, reflecting a 4% difference that met the noninferiority threshold of 7% (P = .039), Dr. Abu Hilal reported.
About DIPLOMA
The European Consortium on Minimally Invasive Pancreatic Surgery designed the phase III DIPLOMA trial to establish the efficacy and safety of minimally invasive distal pancreatectomy. As Dr. Abu Hilal pointed out, the use of the minimally invasive approach has been increasing since the mid-1990s. Its benefits include quicker time to functional recovery and shorter hospital stay, but there have been concerns about lymph node yield, achievement of radical resection, and survival.
“Additionally, there have been other randomized trials in other surgical fields that have failed to show advantages for minimally invasive surgical approaches. Hence, there has been a need to answer the question about the validity of minimally invasive surgery as an alternative approach,” he said.
Between May 2018 and May 2021, DIPLOMA investigators screened more than 1,100 patients to identify those considered fully resectable without neoadjuvant chemotherapy. They ultimately enrolled 258 patients with resectable pancreatic cancer from 35 centers in 12 countries (mostly European).
KEY POINTS
The multicenter, patient-blinded, phase III DIPLOMA trial was a noninferiority trial that evaluated outcomes with open vs minimally invasive distal pancreatectomy in resectable, early-stage pancreatic cancer.
DIPLOMA is the first randomized trial to compare these approaches in terms of oncologic outcomes.
The primary endpoint, R0 resection rate, was achieved by 73% of the minimally invasive group and 69% of the open surgery group, reflecting noninferiority.
Other outcomes—lymph node retrieval, intraperitoneal recurrence, survival, disease-free survival, and functional recovery—were also similar.
Patients were randomly assigned to minimally invasive surgery (laparoscopic or robotic) or open distal pancreatectomy to remove tumors on the body or tail of the pancreas along with the spleen. Both the patient and the pathologist who examined the samples were blind to the type of surgery received (via abdominal dressing).
The primary endpoint was R0 resection, with a 7% or less difference set as a threshold for noninferiority. “We acknowledge that survival would have been the best endpoint, but thousands of patients would have been needed for this,” stated Dr. Abu Hilal. “R0 resection has been associated very closely with survival.”
The intent-to-treat population included 117 in the minimally invasive group and 127 in the open pancreatectomy group. Follow-up ranged from 2 weeks to 12 months.
Other Outcomes Were Comparable
After surgery, in addition to the comparable R0 resection rate, all other relevant outcomes were similar as well:
- The median lymph node yield was 22 in the minimally invasive group and 23 in the open surgery group (P = .89). The minimum lymph node yield for a successful distal pancreatectomy is 13 lymph nodes.
- Intraperitoneal recurrence was 41% in the minimally invasive group and 38% in the open surgery group.
- Median overall survival was 40 months for the minimally invasive group and 39 months for the open surgery group (P = .94).
- Median disease-free survival was 44 months and 45 months, respectively (P = .88).
- Time to functional recovery was 5 days in each group (P = .22).
- Serious adverse events were seen in 18% of the minimally invasive surgery group and 22% of the open surgery group (P = .45).
At the press briefing, Dr. Abu Hilal told journalists that minimally invasive pancreatectomy is becoming a common approach in high-volume or specialized surgical centers, with several centers in the United States “leading the world” in this technique, especially robotic surgery. “Now, we have data that support it…. We have some codification for its use and strong evidence to increase its practice.”
Researchers will continue to follow these patients to compare outcomes at 3 and 5 years, to analyze the importance of removing the spleen for retrieval of lymph nodes, and to determine the relative benefits of laparoscopic vs robotic surgery.
DISCLOSURE: Dr. Abu Hilal has received research funding from Ethicon and Medtronic.
REFERENCE
1. Abu Hilal M, Korrel M, Jones L, et al: Minimally invasive versus open distal pancreatectomy for resectable pancreatic cancer (DIPLOMA): An international randomised trial. 2020 ASCO Annual Meeting. Abstract 4163. Presented June 5, 2023.
