title: Resection versus other treatments for locally advanced pancreatic cancer.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  To compare the benefits and harms of surgical resection versus palliative treatment in patients with locally advanced pancreatic cancer.
  
  
  METHODS
  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.
  
  
  METHODS
  We included randomised controlled trials comparing pancreatic resection versus palliative treatments for patients with locally advanced pancreatic cancer (irrespective of language or publication status).
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Surgery, Royal Free Campus, UCL Medical School, Royal Free Hospital, Rowland Hill Street, London, UK, NW3 2PF.
authors.forename: Kurinchi Selvan
authors.initials: KS
authors.lastname: Gurusamy
authors.forename: Senthil
authors.initials: S
authors.lastname: Kumar
authors.forename: Brian R
authors.initials: BR
authors.lastname: Davidson
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Fusai
mesh_terms: D059186:Chemoradiotherapy, Adjuvant; D006801:Humans; D007167:Immunotherapy / Q000379:methods; D008197:Lymph Node Excision; D010166:Palliative Care / Q000379:methods*; D010179:Pancreas / Q000098:blood supply / Q000601:surgery*; D010180:Pancreatectomy / Q000379:methods; D010190:Pancreatic Neoplasms / Q000098:blood supply / Q000401:mortality / Q000628:therapy*; D016577:Pancreaticoduodenectomy / Q000379:methods; D016032:Randomized Controlled Trials as Topic; D013156:Splenectomy; D015996:Survival Rate