Neoadjuvant chemotherapy improves survival in patients with oesophageal mucinous adenocarcinoma: Post-hoc analysis of the UK MRC OE02 and OE05 trials.

BACKGROUND

Adenocarcinoma with more than 50% extracellular mucin is a relatively rare histological subtype of gastrointestinal adenocarcinomas. The clinical impact of extracellular mucin in oesophageal adenocarcinoma (OeAC) has not been investigated in detail. We hypothesised that patients with mucinous OeAC (OeAC) do not benefit from neoadjuvant chemotherapy.

METHODS

OeAC patients either treated by surgery alone in the OE02 trial (S-patients) or by neoadjuvant chemotherapy followed by surgery (CS-patients) in OE02 or OE05 trials were included. Cancers from 1055 resection specimens (OE02 [test cohort]: 187 CS, 185 S; OE05 [validation cohort]: 683 CS) were classified as either mucinous (more than 50% of the tumour area consists of extracellular mucin, OeAC) or non-mucinous adenocarcinoma (OeAC). The relationship between histological phenotype, clinicopathological characteristics, survival and treatment was analysed.

RESULTS

Overall, 7.3% and 9.6% OeAC were classified as OeAC in OE02 and OE05, respectively. In OE02, the frequency of OeAC was similar in S and CS-patients. Patients with OeAC treated with surgery alone had a poorer overall survival compared with OeAC patients (hazard ratio: 2.222, 95% confidence interval: 1.08-4.56, P = 0.025). Patients with OeAC treated with neoadjuvant chemotherapy and surgery had similar survival as OeAC patients in test and validation cohort.

CONCLUSIONS

This is the first study to suggest in a post-hoc analysis of material from two independent phase III clinical trials that the poor survival of patients with mucinous OeAC can be improved by neoadjuvant chemotherapy. Future studies are warranted to identify potential underlying biological, biochemical or pharmacokinetic interactions between extracellular mucin and chemotherapy.