10-year Outcome of a Randomized Trial Comparing Neoadjuvant Chemoradiotherapy and Surgery with Surgery Alone for Esophageal Cancer (CROSS trial)

Background: Neoadjuvant chemoradiotherapy according to the Chemo-Radiotherapy for Oesophageal cancer followed by Surgery Study (CROSS)has become a standard of care for patients with locally advanced resectableesophageal or junctional cancer. However, the long-term benefits andharms remain unclear.We aimed to assess the long-term outcomes of thisregimen.Materials and Methods: From 2004 through 2008, 366 patients wererandomly assigned to either five weekly cycles of intravenous carboplatin(area under the curve of 2 mg/mL/min) and paclitaxel (50 mg/m2 bodysurfacearea) on days 1, 8,15, 22, and 29 with concurrent radiotherapy (41.4Gy in 23 fractions, 5 days per week) followed by surgery, or surgery alone.Follow-up data were collected through 2018. Overall survival was estimatedwith the Kaplan-Meier method and compared with Cox regressionanalyses. The effect beyond 5 years of follow-up was assessed by usinglandmark analyses. Also, cause-specific mortality was estimated with cumulativeincidence functions and compared with Cox regression.Results: The median follow-up was 147 months (IQR 134-157). Patientswho received neoadjuvant chemoradiotherapy had better overall survival(HR 0.70, 95%CI 0.55-0.89), with 10-year overall survival of 38% (95%CI 31-45) in the neoadjuvant chemoradiotherapy plus surgery arm and 25% (95%CI 19-32) in the surgery alone arm. Landmark analyses showed that theoverall survival benefit that was gained in the first 5 years, persistedbeyond 5 years. The risk of death from esophageal cancer was lower forpatients who received neoadjuvant chemoradiotherapy plus surgery (HR0.60, 95% CI 0.46-0.80), while death from other causes was comparablebetween both study arms (HR 1.17, 95%CI 0.68-1.99).Conclusions: The overall survival benefit of patients with locally advancedresectable esophageal or esophagogastric junctional cancer who receivedneoadjuvant chemoradiotherapy plus surgery according to the CROSSregimen persists for at least 10 years, compared with surgery alone