Long-Term Results Confirm Superior Outcomes of Neoadjuvant Chemoradiotherapy for Esophageal Cancer

Long-term results of the CROSS study have confirmed that neoadjuvant chemoradiotherapy added to surgery should be the standard of care for patients with resectable esophageal or esophagogastric junction carcinoma.

With a minimum follow-up of 5 years, results showed that patients assigned to neoadjuvant chemoradiotherapy prior to surgery had an overall and progression-free survival benefit compared with patients assigned to surgery alone.

“These long-term results, after a median follow-up for surviving patients of 84 months, confirm the initially reported survival benefit for neoadjuvant chemoradiotherapy plus surgery compared with surgery alone,” wrote study author Joel Shapiro, MD, of Erasmus Medical Center, Rotterdam, Netherlands, and colleagues in Lancet Oncology.

The CROSS study included 368 patients with clinically resectable and locally advanced esophageal or esophagogastric junction carcinoma. Patients were randomly assigned to 5 weekly cycles of neoadjuvant chemoradiotherapy (carboplatin plus paclitaxel followed by 41.4 Gy given in 23 fractions) followed by surgery or to surgery alone. Ninety-five percent of patients in the study were able to complete the entire neoadjuvant chemoradiotherapy regimen.

The initial results of the study were published in 2012 with a follow-up of 2 years and showed an absolute benefit in 5-year overall survival in favor of the neoadjuvant group.

At the final analysis, 41% of patients in the neoadjuvant group and 28% of patients in the surgery alone group were still alive. The updated results with a median follow-up of 84.1 months showed a median overall survival of 48.6 months for patients assigned neoadjuvant treatment compared with 24 months for the surgery alone group (hazard ratio [HR], 0.68 [95% confidence interval (CI), 0.53–0.88]; log rank P = .003). This improvement was seen in patients with both the squamous cell carcinoma subtype (81.6 vs 21.1 months; HR, 0.48 [95% CI, 0.28–0.83]; log rank P = .008) and in patients with adenocarcinomas (43.2 vs 27.1 months; HR, 0.73 [95% CI, 0.55–0.98]; log rank P = .038).

The median progression-free survival was 37.7 months in the neoadjuvant group compared with 16.2 months in the surgery alone group (HR, 0.64 [95% CI, 0.49–0.82]). Similar to overall survival, these improvements in progression-free survival were seen in patients with squamous cell (74.7 vs 11.6 months; HR, 0.48 [95% CI, 0.28–0.82]) and adenocarcinoma (29.9 vs 17.7 months; HR, 0.69 [95% CI, 0.52–0.92]) subtypes.

According to the study, the estimated number of patients needed to be treated to prevent one additional death at 5 years was 7.1 and the number needed to prevent one additional disease progression was 6.1.

In an accompanying commentary, Christophe Mariette, MD, PhD, of Claude Huriez University Hospital, Lille, France, and colleagues wrote that before the regimen used in the CROSS trial can be considered the gold standard, more data are needed confirming the results.

“The findings should be reproduced in non-selected populations, including earlier tumor stages, patients with squamous cell or supracarinal cancers, and those with poorer performance status,” they wrote. “A direct comparison of the CROSS regimen and the fluorouracil–platinum compound and 45 Gy radiotherapy regimen is also needed to understand which benefits are attributable to the neoadjuvant chemoradiotherapy regimen and which to patient selection.”