Background
The pancreas is an organ in the abdomen which secretes digestive juices for the digestion of food. It also harbours the insulin secreting cells which maintain the blood sugar levels. Pancreatic cancer is an aggressive cancer. Surgery to remove the cancer improves survival. However, a third of patients with pancreatic cancer have locally advanced cancer involving major blood vessels which are not usually removed because of the fear of increased complications after surgery. Such patients receive palliative treatment. Resection (removing part of an organ) of the pancreas has been suggested as an alternative to palliative treatment for patients with locally advanced pancreatic cancer. However, in this group of patients the benefits and harms of surgical resection versus other treatments are not clear. We set out to answer this question by performing a thorough search of the literature for studies which compared surgical removal with palliative treatments. We included only randomised controlled trials, studies which, if designed appropriately, can help avoid arriving at wrong conclusions. We searched the literature for all studies reported until December 2013. Two authors independently assessed the trials for inclusion and independently extracted data to minimise errors.
Characteristics of studies
We identified two trials comparing surgical removal of the pancreas versus other treatments for patients with locally advanced pancreatic cancer. Ninety eight patients were included in these two trials. Forty seven patients received surgery while the remaining patients received palliative treatment. The choice of who received surgery and who received other treatments was decided by a method similar to the toss of a fair coin.
Main results
Approximately 97% of patients who underwent cancer removal surgery survived the surgery in the two trials. The patients who received surgery were twice as likely to live as those who received other treatments. The survivors were followed until at least five years. There were no survivors at two years in the palliative treatment group while approximately 40% of the patients who underwent surgical removal were alive at the end of three years. This difference in survival was statistically significant. The studies did not report the complications related to surgery although it is likely that a significant proportion of patients suffered from complications in both groups. None of the trials reported quality of life. There was no evidence of any difference in the length of total hospital stay (which included all admissions of a patient related to the treatment) between the two groups. The total treatment costs were significantly lower in the surgical removal group (by about USD 10,000) than in the palliative treatment group in the trial conducted in Japan. There was no information about the costs in the other trial, which was conducted in Greece.
Quality of evidence
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.
Conclusions
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.
Future research
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.
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.
Pancreatic cancer is an aggressive cancer. Resection of the cancer is the only treatment with the potential to achieve long-term survival. However, a third of patients with pancreatic cancer have locally advanced cancer involving adjacent structures such as blood vessels which are not usually removed because of fear of increased complications after surgery. Such patients often receive palliative treatment. Resection of the pancreas along with the involved vessels is an alternative to palliative treatment for patients with locally advanced pancreatic cancer.
To compare the benefits and harms of surgical resection versus palliative treatment in patients with locally advanced pancreatic cancer.
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2013, Issue 12), MEDLINE, EMBASE, Science Citation Index Expanded, and trial registers until February 2014.
We included randomised controlled trials comparing pancreatic resection versus palliative treatments for patients with locally advanced pancreatic cancer (irrespective of language or publication status).
Two authors independently assessed trials for inclusion and independently extracted the data. We analysed the data with both the fixed-effect and random-effects models using Review Manager (RevMan). We calculated the hazard ratio (HR), risk ratio (RR) or mean difference (MD) with 95% confidence intervals (CI) based on an intention-to-treat analysis.
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).