Neoadjuvant chemoradiotherapy followed by surgical resection should be regarded as the standard of care for patients with locally advanced resectable esophageal or esophagogastric junction cancer, according to the results of a randomized, controlled trial.
Patients with squamous cell carcinoma and adenocarcinoma subtypes derived clinical benefit from this treatment, according to the researchers.
“Esophageal cancer is an aggressive disease, characterized by a high degree of locoregional and distant recurrence after primary surgical resection and poor 5-year OS that rarely exceeds 40%,” Joel Shapiro, MD, PhD, of the department of surgery at Erasmus MC University Medical Center in Rotterdam, Netherlands, and colleagues wrote. “Much effort has been put into improving tumor resectability, long-term locoregional control and OS through the addition of chemotherapy, radiotherapy or both to surgery, in a neoadjuvant or adjuvant setting. However, many studies have not shown a significant long-term survival benefit of such approaches.”
The CROSS trial compared neoadjuvant chemoradiotherapy followed by surgery with surgery alone in patients with squamous cell carcinoma or adenocarcinoma of the esophagus or esophagogastric junction. Initial results showed a significant increase in 5-year OS among patients in the chemoradiotherapy arm after a median follow-up of 45 months.
The final analysis included data from 366 patients (median age, 60 years) with clinically resectable, locally advanced esophageal or esophagogastric junction cancer.
Shapiro and colleagues randomly assigned 178 patients to five weekly cycles of neoadjuvant chemotherapy (IV carboplatin [area under the curve, 2 mg/mL per minute] and IV paclitaxel [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. The other 188 patients underwent surgery alone.
OS served as the primary endpoint.
Median follow-up was 84.1 months (range, 61.1-116.8; interquartile range, 70.7-96.6).
Ninety-five percent of patients (n = 162) completed the entire neoadjuvant chemoradiotherapy regimen.
Researchers reported median OS of 48.6 months (95% CI, 32.1-65.1) among patients assigned to neoadjuvant chemotherapy and 24 months (95% CI, 14.2-33.7) among patients assigned surgery alone (HR = 0.68; 95% CI, 0.53-0.88).
Neoadjuvant radiotherapy conferred statistically significant improvements in median OS among patients with squamous cell carcinoma (81.6 months vs. 21 months; P = .008) and those with adenocarcinomas (43.2 months vs. 27.1 months; P = .038).
Patients assigned to neoadjuvant chemoradiotherapy achieved a longer median PFS than patients assigned surgery alone (37.7 months vs. 16.2 months). Chemoradiotherapy conferred longer median PFS among patients with squamous cell carcinoma (74.7 months vs. 11.6 months) and adenocarcinomas (29.9 months vs. 17.7 months).
Sixteen patients died from treatment-related causes during follow-up; of these, nine were assigned to chemoradiotherapy and seven underwent surgery alone. Further, 23 patients died from non–treatment-related causes (neoadjuvant chemoradiotherapy, n = 13; surgery alone, n = 10).
Researchers reported 116 patients remained alive and disease free at final analysis. They included 39% (n = 69) of patients assigned to neoadjuvant chemoradiotherapy and 25% (n = 47) of patients assigned to surgery alone.
“Results from this trial might not be readily extrapolated to patients with poorer performance status, older patients, or those with tumors located in the proximal or middle esophagus because of the relative scarcity of patients in these categories,” Shapiro and colleagues wrote. “The value of this treatment regimen will need to be confirmed for these patients in future follow-up studies.”
Still, the OS benefits associated with neoadjuvant chemoradiotherapy plus surgery in the analyzed population suggest the regimen should be the standard of care for patients with resectable locally advanced esophageal or junctional cancer, the researchers concluded.
In an accompanying editorial, Christophe Mariette, MD, of the department of digestive and oncological surgery at Claude Huriez University Hospital in Lille, France, and colleagues highlighted the imbalance in outcomes among histologic types.
“Do these results mean that this particular chemoradiation regimen should be the sole standard treatment for this type of cancer?” Mariette and colleagues wrote. “Several issues need to be resolved before we can make this conclusion. First, the survival benefit of neoadjuvant chemotherapy for esophagogastric adenocarcinomas has been well demonstrated. … Second, although 75% of enrolled patients had an adenocarcinoma, the effect of neoadjuvant chemoradiotherapy was much greater in the smaller subgroup of patients with squamous cell carcinoma. … This finding emphasizes the fact that although neoadjuvant chemoradiotherapy benefited some patients with adenocarcinoma, many did not derive such a large benefit.” – by Cameron Kelsall
Disclosure: Shapiro reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures. Mariette and colleagues report no relevant financial disclosures.