Long-Term Results of Dutch CROSS Trial Indicate Continued Survival Benefit With Neoadjuvant Chemoradiotherapy in Esophageal Cancer


Key Points

  • Long-term follow-up confirms the benefit of adding neoadjuvant chemoradiation to surgery in patients with squamous cell carcinoma or adenocarcinoma of the esophagus or esophagogastric junction.
  • Significant benefit was observed among both patients with squamous cell carcinoma and those with adenocarcinoma.

Initial results of the Dutch phase III CROSS trial showed a significant 5-year overall survival benefit with the addition of neoadjuvant chemoradiotherapy to surgery after a median 45-month follow-up in patients with squamous cell carcinoma or adenocarcinoma of the esophagus or esophagogastric junction. As reported in The Lancet Oncology by Shapiro et al, long-term follow-up in the trial shows continued survival benefit with neoadjuvant treatment.

Study Details

In the trial, patients from eight centers in the Netherlands with clinically resectable, locally advanced squamous cell carcinoma (23% of patients) or adenocarcinoma (75% of patients) of the esophagus or esophagogastric junction (clinical stage T1,N1,M0 or T2-3,N0-1,M0) were randomly assigned between March 2004 and December 2008 to receive weekly administration of five cycles of neoadjuvant chemoradiotherapy (carboplatin at AUC = 2 mg/mL/min and paclitaxel at 50 mg/m2 for 23 days) with concurrent radiotherapy (41.4 Gy in 23 fractions of 1.8 Gy 5 days per week) followed by surgery (n = 180) or surgery alone (n = 188). The primary endpoint was overall survival on intent-to-treat analysis.

Overall Survival Benefit

In the current analysis, minimum follow-up was 5 years and median follow-up was 84.1 months in surviving patients. Median overall survival was 48.6 months in the neoadjuvant group vs 24.0 months in the surgery-alone group (hazard ratio [HR] = 0.68, P = .003). Significant benefits for neoadjuvant treatment were observed both among patients with squamous cell carcinoma (median overall survival = 81.6 vs 21.1 months, HR = 0.48, P= .008) and among those with adenocarcinoma (median overall survival = 43.2 vs 27.1 months, HR = 0.73, P = .038).

The investigators concluded: “Long-term follow-up confirms the overall survival benefits for neoadjuvant chemoradiotherapy when added to surgery in patients with resectable oesophageal or oesophagogastric junctional cancer. This improvement is clinically relevant for both squamous cell carcinoma and adenocarcinoma subtypes. Therefore, neoadjuvant chemoradiotherapy according to the CROSS trial followed by surgical resection should be regarded as a standard of care for patients with resectable locally advanced oesophageal or oesophagogastric junctional cancer.”

Joel Shapiro, MD, of Erasmus MC-University Medical Centre, is the corresponding author for the Lancet Oncology article.

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

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