O200 10-YEAR FOLLOW-UP OF A RANDOMISED CONTROLLED TRIAL COMPARING NEOADJUVANT CHEMORADIOTHERAPY PLUS SURGERY VERSUS SURGERY ALONE FOR OESOPHAGEAL OR JUNCTIONAL CANCER (CROSS)

Aim To report the long term results of the CROSS trial with a minimum follow-up of 10 years. Background Neoadjuvant chemoradiotherapy according to the Dutch randomised controlled ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) has become standard of care for patients with cancer of the oesophagus or oesophagogastric junction. Methods Patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction were randomised between neoadjuvant chemoradiotherapy (five weekly cycles of intravenous carboplatin [AUC 2 mg/mL per min] and intravenous paclitaxel [50 mg/m² of body-surface area]) with concurrent 41.4 Gy radiotherapy given in 23 fractions of 1.8 Gy, 5 days per week) plus surgery versus surgery alone. Primary endpoint was overall survival, defined from date of randomisation to date of all-cause death or to last day of follow-up. Analysis was by intention-to-treat. Results Between March 2004 and 2008, eight centres enrolled 368 patients. Some 178 were analysed in the chemoradiotherapy plus surgery group and 188 in the surgery alone group. After a median follow-up for surviving patients of 146.6 months (IQR 133.5-156.6), median overall survival was 49.0 months (95%CI 34.7-76.6) in the neoadjuvant chemoradiotherapy plus surgery group compared to 25.1 months (95%CI 19.1-39.4) in the surgery alone group, which was significantly different (HR 0.71 [95%CI 0.55-0.90]; log-rank p=0·005). Ten-year overall survival was 38% (95%CI 31%-45%) in the neoadjuvant chemoradiotherapy followed by surgery group compared to 26% (95%CI 20%-33%) in the surgery alone group (HR 0.69 [95%CI 0.54-0.89]). For patients with squamous cell carcinoma ten-year overall survival was 46% (95%CI 33%-64%) in the neoadjuvant chemoradiotherapy plus surgery group compared to 23% (95%CI 13%-40%) in the surgery alone group. For patients with adenocarcinoma ten-year overall survival was 36% (95%CI 29%-45%) in the neoadjuvant chemoradiotherapy plus surgery group compared to 26% (95%CI 20%-35%) in the surgery alone group. Conclusion Survival benefit of patients with locally advanced resectable squamous cell carcinoma or adenocarcinoma of the oesophagus or oesophagogastric junction receiving neoadjuvant chemoradiotherapy persists for at least 10 years compared to patients undergoing surgery alone.