title: Non-surgical versus surgical treatment for oesophageal cancer.
abstract: BACKGROUND
  Oesophageal cancer is the sixth most common cause of cancer-related mortality in the world. Currently surgery is the recommended treatment modality when possible. However, it is unclear whether non-surgical treatment options is equivalent to oesophagectomy in terms of survival.
  
  
  OBJECTIVE
  To assess the benefits and harms of non-surgical treatment versus oesophagectomy for people with oesophageal cancer.
  
  
  METHODS
  We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, Science Citation Index, ClinicalTrials.gov, and the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) up to 4th March 2016. We also screened reference lists of included studies.
  
  
  METHODS
  Two review authors independently screened all titles and abstracts of articles obtained from the literature searches and selected references for further assessment. For these selected references, we based trial inclusion on assessment of the full-text articles.
  
  
  METHODS
  Two review authors independently extracted study data. We calculated the risk ratio (RR) with 95% confidence interval (CI) for binary outcomes, the mean difference (MD) or the standardised mean difference (SMD) with 95% CI for continuous outcomes, and the hazard ratio (HR) for time-to-event outcomes. We performed meta-analyses where it was meaningful.
  
  
  RESULTS
  Eight trials, which included 1132 participants in total, met the inclusion criteria of this Cochrane review. These trials were at high risk of bias trials. One trial (which included five participants) did not contribute any data to this Cochrane review, and we excluded 13 participants in the remaining trials after randomisation; this left a total of 1114 participants, 510 randomised to non-surgical treatment and 604 to surgical treatment for analysis. The non-surgical treatment was definitive chemoradiotherapy in five trials and definitive radiotherapy in three trials. All participants were suitable for major surgery. Most of the data were from trials that compared chemoradiotherapy with surgery. There was no difference in long-term mortality between chemoradiotherapy and surgery (HR 0.88, 95% CI 0.76 to 1.03; 602 participants; four studies; low quality evidence). The long-term mortality was higher in radiotherapy than surgery (HR 1.39, 95% CI 1.18 to 1.64; 512 participants; three studies; very low quality evidence). There was no difference in long-term recurrence between non-surgical treatment and surgery (HR 0.96, 95% CI 0.80 to 1.16; 349 participants; two studies; low quality evidence). The difference between non-surgical and surgical treatments was imprecise for short-term mortality (RR 0.39, 95% CI 0.11 to 1.35; 689 participants; five studies; very low quality evidence), the proportion of participants with serious adverse in three months (RR 0.61, 95% CI 0.25 to 1.47; 80 participants; one study; very low quality evidence), and proportion of people with local recurrence at maximal follow-up (RR 0.89, 95% CI 0.70 to 1.12; 449 participants; three studies; very low quality evidence). The health-related quality of life was higher in non-surgical treatment between four weeks and three months after treatment (Spitzer Quality of Life Index; MD 0.93, 95% CI 0.24 to 1.62; 165 participants; one study; very low quality evidence). The difference between non-surgical and surgical treatments was imprecise for medium-term health-related quality of life (three months to two years after treatment) (Spitzer Quality of Life Index; MD -0.95, 95% CI -2.10 to 0.20; 62 participants; one study; very low quality of evidence). The proportion of people with dysphagia at the last follow-up visit prior to death was higher with definitive chemoradiotherapy compared to surgical treatment (RR 1.48, 95% CI 1.01 to 2.19; 139 participants; one study; very low quality evidence).
  
  
  CONCLUSIONS
  Based on low quality evidence, chemoradiotherapy appears to be at least equivalent to surgery in terms of short-term and long-term survival in people with oesophageal cancer (squamous cell carcinoma type) who are fit for surgery and are responsive to induction chemoradiotherapy. However, there is uncertainty in the comparison of definitive chemoradiotherapy versus surgery for oesophageal cancer (adenocarcinoma type) and we cannot rule out significant benefits or harms of definitive chemoradiotherapy versus surgery. Based on very low quality evidence, the proportion of people with dysphagia at the last follow-up visit prior to death was higher with definitive chemoradiotherapy compared to surgery. Based on very low quality evidence, radiotherapy results in less long-term survival than surgery in people with oesophageal cancer who are fit for surgery. However, there is a risk of bias and random errors in these results, although the risk of bias in the studies included in this systematic review is likely to be lower than in non-randomised studies.Further trials at low risk of bias are necessary. Such trials need to compare endoscopic treatment with surgical treatment in early stage oesophageal cancer (carcinoma in situ and Stage Ia), and definitive chemoradiotherapy with surgical treatments in other stages of oesophageal cancer, and should measure and report patient-oriented outcomes. Early identification of responders to chemoradiotherapy and better second-line treatment for non-responders will also increase the need and acceptability of trials that compare definitive chemoradiotherapy with surgery.
authors.affiliation: Department of Surgery, Royal Free Campus, UCL Medical School, Rowland Hill Street, London, UK, NW32PF.
authors.forename: Lawrence M J
authors.initials: LM
authors.lastname: Best
authors.forename: Muntzer
authors.initials: M
authors.lastname: Mughal
authors.forename: Kurinchi Selvan
authors.initials: KS
authors.lastname: Gurusamy
mesh_terms: D059248:Chemoradiotherapy / Q000401:mortality; D004938:Esophageal Neoplasms / Q000401:mortality / Q000628:therapy*; D006304:Health Status; D006801:Humans; D011788:Quality of Life; D011878:Radiotherapy / Q000401:mortality; D016032:Randomized Controlled Trials as Topic