In operable esophageal cancer, does two-cycle neoadjuvant cisplatin/5-FU improve survival compared with surgery alone? [MRC OE02]
In operable esophageal cancer, does two-cycle neoadjuvant cisplatin/5-FU improve survival compared with surgery alone?
Absolute Effect
Median OS was 16.8 vs 13.3 months; long-term HR 0.84 (95% CI 0.72–0.98), P=.03. Five-year OS was 23.0% vs 17.1%.
Absolute effect: Five-year OS improved by 5.9 percentage points (23.0% vs 17.1%). R0 resection increased from 54% to 60%.
NNT: 17, based on 5-year overall survival (absolute improvement 5.9 percentage points).
NNH: not quantifiable from the primary report because a single fixed-time serious toxicity endpoint was not reported in a form suitable for a defensible NNH.
Follow-up: Long-term follow-up confirmed persistent survival benefit.
Clinical results and treatment burden
- Intervention: Two 3-weekly cycles of cisplatin plus continuous-infusion 5-FU before surgery versus immediate surgery.
- Principal toxicity: The major treatment burden was preoperative cisplatin/5-FU toxicity and the possibility of treatment-related morbidity delaying surgery; operative outcomes did not erase the survival benefit.
- Other efficacy/recurrence findings: The survival effect was consistent across adenocarcinoma and squamous histologies in the long-term analysis, although subsequent trials showed that chemoradiotherapy and perioperative strategies may be preferable in particular anatomical/histological settings.
- Quality of life: QoL was not the principal endpoint; the trial's patient-centred value lies mainly in survival and successful R0 resection.
Eligibility and clinical context
802 patients with treatment-naïve, resectable esophageal cancer; approximately two thirds had adenocarcinoma and one third squamous carcinoma.
Limitations and maturity: Later randomized trials have produced heterogeneous results for neoadjuvant chemotherapy, particularly in squamous disease. Modern practice also incorporates PET/CT, MRI, molecular staging and chemoradiotherapy/perioperative FLOT depending on tumour location and histology.