Is Controversy Over NCRT Plus Surgery Warranted in Esophageal Squamous Cell Carcinoma?

Neoadjuvant chemoradiotherapy (NCRT) plus surgery significantly improves survival vs surgery alone in locally advanced esophageal squamous cell carcinoma (ESCC), with acceptable and manageable adverse events, according to a new study.

Controversy has surrounded the use of NCRT plus surgery to treat ESCC, the authors reported in the Journal of Clinical Oncology. Therefore, they wrote, these new findings are particularly important in potentially changing guidelines and making treatment decisions for patients with potentially resectable, locally advanced ESCC.

Investigators conducted a phase III, multicenter, randomized, open-label clinical trial evaluating 451 patients who were treated between June 2007 and December 2014. They found that, compared with surgery alone, NCRT plus surgery is safe and significantly prolongs overall survival (OS) and disease-free survival (DFS) in patients with locally advanced ESCC.

All patients were diagnosed with potentially resectable thoracic ESCC that was clinically staged as T1-4N1M0/T4N0M0. They were randomly allocated to NCRT plus surgery (n = 224) or surgery alone (n = 227). Patients in the CRT arm received vinorelbine 25 mg/m2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m² IV on day 1, or 25 mg/m² IV on days 1 to 4 every 3 weeks for two cycles. The patients concurrently received a radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy 5 days per week. All patients underwent McKeown or Ivor Lewis esophagectomy.

The pathologic complete response rate (CRR) was 43.2% in the CRT arm. In this study, the median follow-up was 41.0 months in the CRT arm and 34.6 months in the surgery-only arm. Using a Kaplan-Meier analysis for OS, the researchers found there was a significant difference between the two arms. The CRT arm had a higher R0 resection rate (98.4% vs 91.2%), improved median OS (100.1 months vs 66.5 months), and a prolonged DFS (100.1 months vs 41.7 months).   

During chemoradiotherapy, leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events, and the rates of postoperative complications were similar between the two arms. However, arrhythmias were much more common in the CRT group (13% vs 4.0% for the surgery-alone arm). The peritreatment mortality was 2.2% in the CRT arm vs 0.4% in the surgery-only arm.

Sai Yendamuri, MD, who is the chair of the Department of Thoracic Surgery at Roswell Park Comprehensive Cancer Center in Buffalo, New York, said these study findings are reassuring news and can help better inform clinicians.

“This is a good study for many reasons. The study demonstrates clearly the added benefit of neoadjuvant chemoradiation to surgery for esophageal squamous cell cancer. This treatment approach has become standard in North America over the last decade, although increasingly the common histology in the United States is adenocarcinoma,” Yendamuri told Cancer Network.