Chemoradiotherapy, with adjuvant surgery for local control, confers a durable survival advantage in adenocarcinoma and squamous cell carcinoma of the oesophagus.
BACKGROUND
Oesophageal cancer usually presents with systemic disease, necessitating systemic therapy. Neo-adjuvant chemoradiotherapy improves short-term survival, but its long-term impact is disputed because of limited accrual, treatment-protocol heterogeneity and a short follow-up of randomised trials.


OBJECTIVE
Long-term results of two simultaneous randomised controlled trials (RCTs) comparing neo-adjuvant chemo-radiotherapy and surgery (MMT) with surgical monotherapy were examined, and the response of adenocarcinoma (AC) and squamous cell carcinoma (SCC) to identical regimens compared.


METHODS
Between 1990 and 1997, two RCTs were undertaken on 211 patients. Patients with AC (n=113) or SCC (n=98) were separately-randomised to identical protocols of MMT or surgical monotherapy.


RESULTS
211 patients were followed to 206 months; 104 patients were randomised to MMT (58 AC and 46 SCC, respectively) and 107 to surgery. MMT provided a significant survival-advantage over surgical monotherapy for AC (P=0.004), SCC (P=0.01). There was a 54% relative risk-reduction in lymph-node metastasis following MMT, compared with surgery (64% versus 29%, P<0.001). MMT produced a pathologic complete response (pCR) in 25% and 31% of AC and SCC, respectively. Survival advantage accrued to MMT, pCR and node-negative patients: AC pCR versus surgical monotherapy (P=0.001); residual disease following MMT versus surgical monotherapy (P=0.008); SCC pCR versus surgical monotherapy (P=0.033).


CONCLUSIONS
A survival advantage for MMT persisted long-term in AC and was replicated in SCC. MMT produced loco-regional tumour down-staging to extinction in 25-31% of patients, potentially permitting personalised treatment in this cohort that avoids the morbidity and mortality associated with resection. Node-negative patients with residual localised disease following MMT had a survival advantage over node-negative patients following surgery alone, supporting a systemic effect on micro-metastatic disease.
Royal College of Surgeons in Ireland, Department of Surgery, Connolly Hospital, Dublin 15, Ireland. Electronic address: garybassmd@gmail.com.
G A
GA
Bass
Royal College of Surgeons in Ireland, Department of Surgery, Connolly Hospital, Dublin 15, Ireland.
H
H
Furlong
Department of Surgery, St. James Hospital, Dublin, Ireland.
K E
KE
O'Sullivan
Department of Surgery, St. James Hospital, Dublin, Ireland.
T P J
TP
Hennessy
Royal College of Surgeons in Ireland, Department of Surgery, Connolly Hospital, Dublin 15, Ireland.
T N
TN
Walsh
D000230:Adenocarcinoma / Q000601:surgery* / Q000628:therapy; D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000601:surgery* / Q000628:therapy; D059248:Chemoradiotherapy; D015331:Cohort Studies; D003131:Combined Modality Therapy; D004938:Esophageal Neoplasms / Q000601:surgery* / Q000628:therapy; D004947:Esophagus / Q000187:drug effects / Q000528:radiation effects / Q000601:surgery*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D016019:Survival Analysis; D016896:Treatment Outcome
Long-term survival; Multi-modal therapy; Oesophageal cancer