Neoadjuvant Chemoradiotherapy Followed by Surgery Versus Surgery Alone for Locally Advanced Squamous Cell Carcinoma of the Esophagus (NEOCRTEC5010): A Phase III Multicenter, Randomized, Open-Label Clinical Trial

Abstract

PurposeThe efficacy of neoadjuvant chemoradiotherapy (NCRT) plus surgery for locally advanced esophageal squamous cell carcinoma (ESCC) remains controversial. In this trial, we compared the survival and safety of NCRT plus surgery with surgery alone in patients with locally advanced ESCC.Patients and MethodsFrom June 2007 to December 2014, 451 patients with potentially resectable thoracic ESCC, clinically staged as T1-4N1M0/T4N0M0, were randomly allocated to NCRT plus surgery (group CRT; n = 224) and surgery alone (group S; n = 227). In group CRT, patients received vinorelbine 25 mg/m2 intravenously (IV) on days 1 and 8 and cisplatin 75 mg/m2 IV day 1, or 25 mg/m2 IV on days 1 to 4 every 3 weeks for two cycles, with a total concurrent radiation dose of 40.0 Gy administered in 20 fractions of 2.0 Gy on 5 days per week. In both groups, patients underwent McKeown or Ivor Lewis esophagectomy. The primary end point was overall survival.ResultsThe pathologic complete response rate was 43.2% in group CRT. Compared with group S, group CRT had a higher R0 resection rate (98.4% v 91.2%; P = .002), a better median overall survival (100.1 months v 66.5 months; hazard ratio, 0.71; 95% CI, 0.53 to 0.96; P = .025), and a prolonged disease-free survival (100.1 months v 41.7 months; hazard ratio, 0.58; 95% CI, 0.43 to 0.78; P < .001). Leukopenia (48.9%) and neutropenia (45.7%) were the most common grade 3 or 4 adverse events during chemoradiotherapy. Incidences of postoperative complications were similar between groups, with the exception of arrhythmia (group CRT: 13% v group S: 4.0%; P = .001). Peritreatment mortality was 2.2% in group CRT versus 0.4% in group S (P = .212).ConclusionThis trial shows that NCRT plus surgery improves survival over surgery alone among patients with locally advanced ESCC, with acceptable and manageable adverse events.

Lymphovascular invasion as an independent prognostic indicator in radically resected thoracic esophageal squamous cell carcinoma

“…More than 90% of esophageal cancer cases have been classified as esophageal squamous cell carcinoma (ESCC) in China and esophageal adenocarcinoma is the predominant type in Western countries . Despite advances made in chemoradiotherapy for ESCC, esophagectomy is still the most effective treatment measure at present . However, more than half of the patients who undergo radical esophagectomy develop locoregional or distant recurrence within three years …”

Comparison of efficacy, safety, and costs between neoadjuvant hypofractionated radiotherapy and conventionally fractionated radiotherapy for esophageal carcinoma

“…Third, the necrosis and fibrosis of tumor tissue after neoadjuvant chemoradiotherapy greatly reduces active tumor cells and the probability of tumor cells shedding, spreading, and planting during surgery, thereby reducing local recurrence rates. Compared with esophagectomy alone, several randomized studies have indicated that this neoadjuvant chemoradiotherapy improves pCR, locoregional control, and survival in patients with esophageal cancer undergoing esophagectomy …”

“…Compared with esophagectomy alone, several randomized studies have indicated that this neoadjuvant chemoradiotherapy improves pCR, locoregional control, and survival in patients with esophageal cancer undergoing esophagectomy. 1,2,7 Conventional fractionated radiotherapy has become the mainstay of preoperative radiotherapy in esophageal cancer. However, the extension of preoperative treatment time and the increase of treatment cost is an issue that must be considered.…”

“…Neoadjuvant chemoradiotherapy has become a promising treatment for patients with stage II or III esophageal cancer. Several studies have reported that its use has improved local control, progression free survival (PFS), and overall survival (OS) in comparison with surgery alone . Conventional fractionated radiotherapy (CFRT) is the most commonly used neoadjuvant option for esophageal cancer, but the efficacy and safety of preoperative hypofractionated radiotherapy (HFRT), which delivers a dose larger than 2 Gray (Gy) per fraction in a lower overall dose, has also been studied in some patients with esophageal cancer .…”

“…Several studies have reported that its use has improved local control, progression free survival (PFS), and overall survival (OS) in comparison with surgery alone. [1][2][3] Conventional fractionated radiotherapy (CFRT) is the most commonly used neoadjuvant option for esophageal cancer, but the efficacy and safety of preoperative hypofractionated radiotherapy (HFRT), which delivers a dose larger than 2 Gray (Gy) per fraction in a lower overall dose, has also been studied in some patients with esophageal cancer. 4,5 These studies have indicated that preoperative HFRT could improve the local control rate of esophageal cancer and potentially increase patient survival compared with surgery alone.…”