CROSS and beyond: a clinical perspective on the results of the randomized ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study.

Despite extensive research efforts oesophageal cancer remains a malignancy with a poor prognosis. Improvement of treatment is urgently needed. Although multimodality treatment for resectable oesophageal cancer has established it place in standard practice, there are still many differences worldwide in the preferred treatment. The Dutch ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) trial has contributed significantly to the current use of neoadjuvant chemoradiation. This study compared neoadjuvant chemoradiotherapy (CRT) using a moderate radiation dose weekly combined with carboplatin and paclitaxel followed by surgery versus surgery alone. Median overall survival in the CRT group is 49.4 months compared to 24.0 months in the surgery alone group, resulting in an overall survival benefit of 13% in favor of the CRT group (HR, 0.81; 95% CI: 0.70-0.93; P=0.002). Recently the results after long-term follow-up (median 60 months) have been published and confirm the benefit of neoadjuvant CRT to surgery alone. Perioperative mortality rates are low and did not increase by adding CRT (4%) and the CROSS scheme has a favorable toxicity profile. Recurrence patterns in patients treated according to the CROSS protocol report significantly reduced loco regional recurrence in the CRT group (34% to 14%; P<0.001) and less peritoneal carcinomatosis (14% to 4%; P<0.001). With the contemporary focus of research on tumor tailored therapy, the effective and safe CROSS protocol serves as a backbone in many ongoing trials.