SUMMARY: The American Cancer Society estimates that in the US, about 16,910 new esophageal cancer cases will be diagnosed in 2016 and about 15,690 patients will die of the disease. Squamous Cell Carcinoma is the most common type of cancer of the esophagus among African Americans, while Adenocarcinoma is more common in caucasians. Previously published trials comparing neoadjuvant concurrent chemoradiation plus surgery to surgery alone, with Cisplatin and 5-FU chemotherapy, have shown conflicting results and this may have been due to small numbers of patients enrolled in these trials. Based on positive outcomes in phase II studies, the ChemoRadiotherapy for Oesophageal cancer followed by Surgery Study (CROSS) was conducted, to compare neoadjuvant chemoradiotherapy plus surgery to surgery alone, in patients with Squamous Cell Carcinoma and Adenocarcinoma of the esophagus or esophagogastric junction. Enrolled patients (N=368) were randomly assigned in a 1:1 ratio and had locally advanced (clinical stage T1N1M0 or clinical stage T2-3N0-1M0) disease. Locoregional sites included mediastinum, supraclavicular and celiac trunk lymph nodes.
Treatment consisted of PARAPLATIN® (Carboplatin) at AUC-2, IV and TAXOL® (Paclitaxel) 50 mg/m2 IV, given weekly for 5 weeks, on days 1,8,15,22 and 29 with concurrent radiotherapy (41.4 Gy, given in 23 fractions of 1.8 Gy, 5 days per week) followed by surgery (N=180), or surgery alone (N=188). The median age was 60 years and patients in the surgery alone group underwent surgery as soon as possible, whereas those receiving neoadjuvant chemoradiation underwent surgery 4-6 weeks following completion of chemoradiation. The primary endpoint of this study was Overall Survival (OS) and secondary endpoints included Progression Free Survival (PFS).
After a median follow up of 84.1 months, the median Overall Survival (OS) for all histologies was 48.6 months in the neoadjuvant chemoradiation plus surgery group and 24 months in the surgery alone group (HR=0.68; P=0.003). The median OS for patients with Squamous Cell Carcinomas was 81.6 months in the neoadjuvant chemoradiation plus surgery group and 21.1 months in the surgery alone group (HR=0.48; P=0.008) and for patients with Adenocarcinomas was 43.2 months in the neoadjuvant chemoradiotherapy plus surgery group and 27.1 months in the surgery alone group (HR=0.73; P=0.038). It is of interest to note that the improvement in distant disease control occurred within the first 2 years following treatment initiation, whereas improvement in locoregional control continued for a longer period of time.
The authors concluded that in patients with resectable, locally advanced, esophageal or esophagogastric junctional cancer, neoadjuvant chemoradiotherapy when added to surgery, confers Overall Survival benefit for both Squamous Cell Carcinoma and Adenocarcinoma histological subtypes and should therefore be regarded as the standard of care, for this patient population. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Shapiro J, van Lanschot JB, Hulshof MM, et al. The Lancet Oncology 2015;16:1090-1098