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Ten-Year Outcomes With Neoadjuvant Chemoradiotherapy Plus Surgery vs Surgery Alone for Esophageal Cancer


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As reported in the Journal of Clinical Oncology by Eyck et al, 10-year follow-up of the Dutch CROSS trial has shown a continued overall survival benefit with neoadjuvant chemoradiotherapy plus surgery vs surgery alone in patients with locally advanced resectable esophageal or gastroesophageal junction cancer.

Study Details

In the multicenter trial, 366 patients were randomly assigned between 2004 and 2008 to receive five weekly cycles of carboplatin at area under the curve = 2 and paclitaxel at 50 mg/m2 with concurrent radiotherapy at 41.4 Gy in 23 fractions for 5 days per week followed by surgery (n = 178) or surgery alone (n = 188). The initial analysis of the trial showed superior 2-year overall survival in the neoadjuvant chemoradiotherapy group, with results being supported by analysis at 5 years.

The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.
— Eyck et al

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Key Findings

Median follow-up was 147 months (interquartile range = 134–157 months).

Ten-year overall survival was 38% in the neoadjuvant treatment group vs 25% in the surgery alone group (hazard ratio [HR] = 0.70, 95% confidence interval [CI] = 0.55–0.89).

Ten-year overall survival rates were 46% vs 23% among patients with squamous cell carcinoma and 36% vs 26% among those with adenocarcinoma.

The effect of neoadjuvant chemoradiotherapy on overall survival was not time-dependent (P = .73 for interaction). Landmark analyses indicated that the major effect of neoadjuvant chemoradiotherapy was observed in the first 5 years of follow-up, with the effect stabilizing thereafter.

Neoadjuvant chemoradiotherapy was associated with reduced risk of death from esophageal cancer, with 10-year absolute risks of 47% vs 64% (HR = 0.60, 95% CI = 0.46–0.80). No significant difference was observed in risk of death from other causes, with 10-year absolute risks of 15% vs 11% (HR = 1.17, 95% CI = 0.68–1.99).

Rates of isolated locoregional relapse at 10 years were 8% vs 18% (HR = 0.40, 95% CI = 0.21–0.72). Rates of synchronous distant plus locoregional relapse were 13% vs 22% (HR = 0.43, 95% CI = 0.26–0.72); rates of isolated distant relapse were 27% vs 28% (HR = 0.76, 95% CI = 0.52–1.13).

The investigators concluded: “The overall survival benefit of patients with locally advanced resectable esophageal or junctional cancer who receive preoperative chemoradiotherapy according to CROSS persists for at least 10 years.”

Ben M. Eyck, MD, of the Department of Surgery, Erasmus MC-University Medical Center Rotterdam, is the corresponding author for the Journal of Clinical Oncology article.

Disclosure: The study was funded by the Dutch Cancer Foundation. For full disclosures of the study authors, visit ascopubs.org.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
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