Abstract: We identified two trials comparing pancreatic resection versus other treatments for patients with locally advanced pancreatic cancer. Ninety eight patients were randomised to pancreatic resection (n = 47) or palliative treatment (n = 51) in the two trials included in this review. Both trials were at high risk of bias. Both trials included patients who had locally advanced pancreatic cancer which involved the serosa anteriorly or retroperitoneum posteriorly or involved the blood vessels. Such pancreatic cancers would be considered generally unresectable. One trial included patients with pancreatic cancer in different locations of the pancreas including the head, neck and body (n = 42). The patients allocated to the pancreatic resection group underwent partial pancreatic resection (pancreatoduodenectomy with lymph node clearance or distal pancreatic resection with lymph node clearance) in this trial; the control group received palliative treatment with chemoradiotherapy. In the other trial, only patients with cancer in the head or neck of the pancreas were included (n = 56). The patients allocated to the pancreatic resection group underwent en bloc total pancreatectomy with splenectomy and vascular reconstruction in this trial; the control group underwent palliative bypass surgery with chemoimmunotherapy. The pancreatic resection group had lower mortality than the palliative treatment group (HR 0.38; 95% CI 0.25 to 0.58, very low quality evidence). Both trials followed the survivors up to at least five years. There were no survivors at two years in the palliative treatment group in either trial. Approximately 40% of the patients who underwent pancreatic resection were alive in the pancreatic resection group at the end of three years. This difference in survival was statistically significant (RR 22.68; 95% CI 3.15 to 163.22). The difference persisted at five years of follow-up (RR 8.65; 95% CI 1.12 to 66.89). Neither trial reported severe adverse events but it is likely that a significant proportion of patients suffered from severe adverse events in both groups. The overall peri-operative mortality in the resection group in the two trials was 2.5%. None of the trials reported quality of life. The estimated difference in the length of total hospital stay (which included all admissions of the patient related to the treatment) between the two groups was imprecise (MD -23.00 days; 95% CI -59.05 to 13.05, very low quality evidence). The total treatment costs were significantly lower in the pancreatic resection group than the palliative treatment group (MD -10.70 thousand USD; 95% CI -14.11 to -7.29, very low quality evidence). There is very low quality evidence that pancreatic resection increases survival and decreases costs compared to palliative treatments for selected patients with locally advanced pancreatic cancer and venous involvement. When sufficient expertise is available, pancreatic resection could be considered for selected patients with locally advanced pancreatic cancer who are willing to accept the potentially increased morbidity associated with the procedure. Further randomised controlled trials are necessary to increase confidence in the estimate of effect and to assess the quality of life of patients and the cost-effectiveness of pancreatic resection versus palliative treatment for locally advanced pancreatic cancer.

Plain-language summary: Overall, the trials were at high risk of bias (that is, there is a potential to arrive at wrong conclusions). This was because it was not clear how the randomisation was performed, whether the people assessing the outcomes were aware of the group to which the participants belonged, and whether all participants were included in the analysis. The overall quality of evidence was very low as the trials were at high risk of bias and there were few trials to assess whether only studies with negative results were published. There is very low quality evidence that surgical resection increases survival and decreases costs compared to palliative treatments for patients with locally advanced pancreatic cancer with involvement of veins. In selected patients pancreatic resection could be considered for patients with locally advanced pancreatic cancer who are willing to accept the potentially increased complications associated with the surgical procedure and when sufficient expertise is available. Further randomised controlled trials are necessary to obtain more precise results and to assess the quality of life of patients and the value for money of surgical removal versus other treatments for locally advanced pancreatic cancer.