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

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 mucin) do not benefit from neoadjuvant chemotherapy. 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 mucin) or non-mucinous adenocarcinoma (OeAC non-mucin). The relationship between histological phenotype, clinicopathological characteristics, survival and treatment was analysed. Overall, 7.3% and 9.6% OeAC were classified as OeAC mucin in OE02 and OE05, respectively. In OE02, the frequency of OeAC mucin was similar in S and CS-patients. Patients with OeAC mucin treated with surgery alone had a poorer overall survival compared with OeAC non-mucin patients (hazard ratio: 2.222, 95% confidence interval: 1.08–4.56, P = 0.025). Patients with OeAC mucin treated with neoadjuvant chemotherapy and surgery had similar survival as OeAC non-mucin patients in test and validation cohort. 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. • Gastrointestinal mucinous adenocarcinoma (AC mucin) has a poorer prognosis. • Response to chemotherapy in oesophageal AC mucin (OeAC mucin) is unclear. • OeAC mucin patients treated with surgery alone have poor survival in OE02 trial. • Neoadjuvant chemotherapy improved survival of OeAC mucin patients in OE02 and OE05. • OeAC mucin patients should be treated with neoadjuvant chemotherapy and surgery. [ABSTRACT FROM AUTHOR]