CRD summary

This review of patients with oesophageal squamous cell cancer found a significant survival benefit for neoadjuvant chemoradiotherapy before surgery with no increase in morbidity rate. Definitive chemoradiotherapy did not demonstrate any survival benefit over other curative strategies. The authors' overall conclusions appear appropriate.

Authors' objectives

To clarify the benefits of neoadjuvant and definitive treatment for oesophageal squamous cell cancer.

Searching

The authors searched Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, BIOSIS Previews and Science Citation Index for trials in English up to the end of March 2010. Search terms were reported. Reference lists of retrieved articles and previously published meta-analyses were also consulted.

Study selection

Randomised controlled trials (RCTs) that compared neoadjuvant chemoradiotherapy (CRT) or chemotherapy with surgery alone, or that compared neoadjuvant treatment/surgery alone versus definitive chemoradiotherapy, in patients with invasive oesophageal cancer (pathologically diagnosed) were eligible for inclusion. Eligible trials had to include patient survival as an outcome. RCTs that included patients with oesophageal adenocarcinoma but reported squamous cell cancer and adenocarcinoma survival data separately were also eligible. Other outcomes of interest were: one-, two-, three- and five-year survival rates; frequency of complete resection; overall morbidity and mortality rates at 30 days; and rates of any type of cancer recurrence.

Included trials that compared neoadjuvant chemoradiotherapy followed by surgery versus surgery alone had a mean patient age of 60.8 years, with men comprising 87% of the population. Trials that involved chemotherapy included patients with a mean age of 62.5 years and 79% of the population were men. In trials that compared definitive chemoradiotherapy versus neoadjuvant treatment followed by surgery or surgery alone, the mean age of patients was 59.1 years and 87% were men. There was marked variation in radiotherapy doses and scheduling and chemotherapy regimens. Surgery was performed between two and eight weeks after completion of neoadjuvant treatment.

Two reviewers independently selected studies for inclusion with any disagreements discussed with a third author.

Assessment of study quality

The quality of included trials was assessed using a standard form and included randomisation procedure, allocation concealment, sample size calculation, consistency of the study population, length and quality of follow-up, rate of patients lost to follow-up, and statistical analysis of individual trials. Only trials with an intention-to-treat analysis were included.

Two reviewers independently assessed study quality with any disagreements discussed with a third author.

Data extraction

Hazard ratios (HRs) with their associated 95% confidence intervals (CIs) were extracted or calculated from the trials.

Two reviewers independently extracted study data with any disagreements discussed with a third author.

Methods of synthesis

Heterogeneity was assessed using Ι² and Χ². Trials were weighted using the inverse variance method and pooled using random-effects models of meta-analysis.

Results of the review

Twenty-eight RCTs were included in the review; 20 RCTs were included in the meta-analysis (3,318 patients). Results of quality assessment were not provided in full but the authors concluded that, although most trials did not provide sufficient details of randomisation, allocation concealment was not compromised. Median follow-up, ranged from 10 months to 98 months (where reported).

Neoadjuvant chemoradiotherapy followed by surgery versus surgery alone (nine RCTs; 1,099 patients, range 56 to 282): The likelihood of complete oesophageal cancer resection (R0, no residual tumour) was significantly greater after neoadjuvant chemoradiotherapy (HR 1.15, 1.00 to 1.32) compared with surgery alone; a high level of heterogeneity was noted (Ι²=84%). Survival after neoadjuvant chemoradiotherapy was statistically significantly greater than after surgery alone (HR 0.81, 0.70 to 0.95); there was no evidence of heterogeneity (Ι²=13%). No statistically significant differences were found in postoperative morbidity and mortality between the treatment groups.

Neoadjuvant chemotherapy followed by surgery versus surgery alone (eight RCTs; 1,707 patients, range 39 to 802): The likelihood of complete R0 cancer resection was significantly greater after neoadjuvant chemotherapy (HR 1.16, 1.05 to 1.30) compared with surgery alone; some heterogeneity was noted (Ι²=48%). No statistically significant differences were found in overall survival, postoperative morbidity and mortality between the treatment groups.

Definitive chemoradiotherapy versus neoadjuvant treatment followed by surgery or surgery alone (three RCTs; 512 patients, range 81 to 259): Mortality risk was lower in the definitive chemoradiotherapy group (HR 7.60, 1.76 to 32.88, p = 0.007); there was no statistically significant heterogeneity (Ι²=0%). There were no statistically significant differences in overall survival or morbidity between treatment groups.

Authors' conclusions

For patients with oesophageal squamous cell cancer, a significant survival benefit for neoadjuvant chemoradiotherapy was evident, with no increase in morbidity rate. Definitive chemoradiotherapy did not demonstrate any survival benefit over other curative strategies.

CRD commentary

This review was based on defined inclusion criteria. A range of information sources were searched to identify trials, but only trials in English were eligible which raised the possibility of missing trials. It appeared that unpublished trials were not eligible for inclusion, which left the review open to publication bias. Study selection, data extraction and quality assessment were carried out in duplicate which helped to minimise reviewer bias. Pooling appeared to be appropriate although a range of different treatment regimens were used.

The authors' overall conclusions appear appropriate.

Implications of the review for practice and research

Practice: The authors did not state any implications for practice.

Research: The authors stated that there was a need to incorporate definitive chemoradiotherapy into future trials.

Funding

Not stated.

Bibliographic details

Kranzfelder M, Schuster T, Geinitz H, Friess H, Buchler P. Meta-analysis of neoadjuvant treatment modalities and definitive non-surgical therapy for oesophageal squamous cell cancer. British Journal of Surgery 2011; 98(6): 768-783. [PubMed: 21462364]

Original Paper URL

http://onlinelibrary.wiley.com/doi/10.1002/bjs.7455/abstract

Indexing Status

Subject indexing assigned by NLM

MeSH

Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell /mortality /therapy; Chemotherapy, Adjuvant; Esophageal Neoplasms /mortality /therapy; Humans; Middle Aged; Patient Care Team; Radiotherapy, Adjuvant; Randomized Controlled Trials as Topic

AccessionNumber

12011004194

Database entry date

26/01/2012

Record Status

This is a critical abstract of a systematic review that meets the criteria for inclusion on DARE. Each critical abstract contains a brief summary of the review methods, results and conclusions followed by a detailed critical assessment on the reliability of the review and the conclusions drawn.