The authors of this paper update a previous meta-analysis in which they had found a survival benefit for neoadjuvant chemoradiotherapy and, to a lesser extent, neoadjuvant chemotherapy before surgery in patients with resectable oesophageal cancer. The meta-analysis has been updated to include the results of recently published or updated trials (in the last 3 years). They conducted a search of the literature for data published since January 2006 and also searched conference abstracts for this period. Studies included in the analysis were restricted to those analysed by intention to treat and in the English language. All trials from the previous meta-analysis were also included (n =17). Seven further studies were identified for inclusion. The meta-analysis was conducted in two sections and the primary outcome measure for the first section was all-cause mortality. The secondary endpoint was the effect on all-cause mortality of treatment for each histological subtype (squamous-cell carcinoma or adenocarcinoma). The second section of the meta-analysis assessed the survival benefits of neoadjuvant chemotherapy compared with neoadjuvant chemoradiotherapy. The authors used hazard ratios (HR) for the comparison in each trial to assess the treatment effects if available or estimates from other data.

The updated analysis contained a total of 4188 patients compared to a total of 2933 patients in the previous publication. With respect to the trials included in the meta-analysis:

• Twelve were randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1854)

• Nine were randomised comparisons of neoadjuvant chemotherapy versus surgery alone (n=1981), and

• Two compared neoadjuvant chemoradiotherapy with neoadjuvant chemotherapy (n=194) in patients with resectable oesophageal carcinoma

One factorial trial included two comparisons and was included in analyses of both neoadjuvant chemoradiotherapy (n=78) and neoadjuvant chemotherapy (n=81).

The results found:

• The updated meta-analysis contained about 3500 events compared with about 2230 in the previous meta-analysis (estimated 57% increase).

• The HR for all-cause mortality for neoadjuvant chemoradiotherapy was 0.78 (95% CI 0.70—0.88; p<0.0001; i.e. a 22% reduction in all cause mortality); the HR for squamous-cell carcinoma only was 0.80 (0.68-0.93; p=0.004) and for adenocarcinoma only was 0.75 (0.59-0.95; p=0.02).

• The HR for all-cause mortality for neoadjuvant chemotherapy was 0.87 (0.79-0.96; p=0.005; i.e. a 13% reduction in all cause mortality); the HR for squamous-cell carcinoma only was 0.92 (0.81-1.04; p=0.18) and for adenocarcinoma only was 0.83 (0.71-0.95; p=0.01).

• The HR for the overall indirect comparison of all-cause mortality for neoadjuvant chemoradiotherapy versus neoadjuvant chemotherapy was 0.88 (0.76-1.01; p=0.07).

The authors write, “Based on present evidence, neoadjuvant chemoradiotherapy improves survival compared with surgery alone for patients with operable oesophageal cancer. Neoadjuvant chemotherapy is also associated with improvements in survival compared with surgery alone and can be deemed a standard treatment. Although the benefit for neoadjuvant chemotherapy was not as great as for neoadjuvant chemoradiotherapy, a clear advantage has not been established and further randomised trials comparing these two strategies directly are warranted.”

The author of a related Comment article discusses the results of this study and summarises, “This clarification of the role of neoadjuvant therapies provides support for a more rational management approach; the default assumption should be that all resectable patients but those with the earliest stage tumours have systemic disease and should receive neoadjuvant chemoradiotherapy. Patients who cannot tolerate trimodal therapy should be offered neoadjuvant chemotherapy. Surgery alone should be reserved for T1 tumours without loco-regional metastases. Patients who achieve a complete clinical response should be restaged, and a policy of intensive observation, rather than surgery, should be considered for elderly patients or those with substantial co-morbidity.”