ArticlesSurvival after neoadjuvant chemotherapy or chemoradiotherapy for resectable oesophageal carcinoma: an updated meta-analysis
Introduction
Overall survival of patients with resectable oesophageal cancer remains poor, with a 5-year survival of 15–34%,1 despite changes in management over the past 20 years. Most patients who undergo radical resection for oesophageal cancer will eventually relapse and die as a result of their disease.2 Because of difficulties in administering chemotherapy or radiotherapy soon after a surgical procedure, high perioperative morbidity, and the disappointing results of trials of adjuvant chemotherapy,3 radiotherapy,4, 5 or combination chemoradiotherapy,2 the focus of recent trials has been on neoadjuvant treatment. In our previous meta-analysis,6 we reported a significant survival benefit for neoadjuvant chemoradiotherapy and, to a lesser extent, neoadjuvant chemotherapy in patients with squamous-cell carcinoma or adenocarcinoma of the oesophagus. At present, there is no evidence supporting the use of neoadjuvant radiotherapy alone.4
Most trials of chemotherapy or combined chemoradiotherapy have used a doublet of cytotoxics, usually a platinum compound, most often cisplatin, and fluorouracil,1, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22 with varying doses and sequencing. Some small trials of neoadjuvant chemotherapy have used triplet chemotherapy, which resulted in increased toxicity without significant survival benefits.23, 24 Recent treatment modifications have included the use of more modern cytotoxic drugs, changes in chemotherapy sequencing, or changes in the dose and fractionation of radiotherapy.2
We aimed to assess whether the results of recently published or updated trials have changed the outcomes of our previous meta-analysis.6 We also sought to compare the benefits of neoadjuvant chemotherapy and neoadjuvant chemoradiotherapy before surgery for resectable oesophageal carcinoma, and to assess whether any increase in survival benefits was offset by an increase in perioperative mortality.
Section snippets
Methods
For the first section of the meta-analysis, we sought to assess the survival benefits of neoadjuvant treatment with either neoadjuvant chemotherapy or neoadjuvant chemoradiotherapy of any regimen. All randomised controlled trials that compared survival after neoadjuvant chemoradiotherapy or neoadjuvant chemotherapy followed by surgery with surgery alone in the initial management of resectable oesophageal or oesophagogastric junction carcinoma (squamous-cell carcinoma, adenocarcinoma, or mixed
Results
We included 24 studies in total (figure 1),1, 7, 8, 9, 10, 11, 12, 13, 14, 15, 17, 18, 19, 20, 21, 22, 23, 24, 37, 39, 40, 41, 42, 43 which consisted of all 17 trials from the previous meta-analysis8, 9, 10, 12, 13, 14, 16, 17, 19, 20, 21, 22, 23, 24, 38, 39, 40 and seven further studies.7, 11, 15, 18, 37, 41, 42 12 were randomised comparisons of neoadjuvant chemoradiotherapy versus surgery alone (n=1854),10, 11, 12, 13, 14, 17, 22, 39, 40, 41, 42, 43 nine were randomised comparisons of
Discussion
Survival benefits of neoadjuvant chemoradiotherapy and neoadjuvant chemotherapy were shown in the previous meta-analysis by our group.6 This updated analysis included updated data on previously published studies and additional studies, with 43% more patients and about 57% more events compared with the previous meta-analysis. The additional information has strengthened the evidence of a survival advantage of neoadjuvant therapy compared with surgery alone. In the present meta-analysis, there is
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