Locally Advanced Esophageal Cancer: Neoadjuvant Chemoradiotherapy vs Chemotherapy Followed by Minimally Invasive Esophagectomy

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In an early analysis from a Chinese phase III trial reported in JAMA Surgery, Wang et al found similar safety and improved histopathologic outcome among patients undergoing minimally invasive esophagectomy for locally advanced esophageal squamous cell carcinoma following neoadjuvant chemoradiotherapy vs neoadjuvant chemotherapy.

Study Details

In the multicenter trial, 264 patients with clinical stages from cT3 to T4aN0 to 1M0 were randomly assigned between January 2017 and December 2018 to receive neoadjuvant chemoradiotherapy (n = 132) or neoadjuvant chemotherapy (n = 132).

Neoadjuvant chemoradiotherapy consisted of paclitaxel at 50 mg/m2 and cisplatin at 25 mg/m2 on days 1, 8, 15, and 22, with external-beam radiation therapy at 40 Gy administered in 20 fractions of 2 Gy, 5 fractions per week, starting on the first day of chemotherapy. Neoadjuvant chemotherapy consisted of two cycles of paclitaxel at 135 mg/m2 and cisplatin at 75 mg/m2 on day 1 given 3 weeks apart.

Minimally invasive esophagectomy by thoracoscopy and laparoscopy was performed at approximately 6 weeks after completion of neoadjuvant therapy. The primary endpoint of the study is 3-year overall survival. The current report presents analyses of early outcomes.

Toxicity and Postoperative Morbidity

During neoadjuvant therapy, the frequency of grade 3 to 4 adverse events was 15.3% in the neoadjuvant chemoradiotherapy group vs 6.9% in the neoadjuvant chemotherapy group (P = .03). Dose delay or reduction was required in 15.3% vs 9.2% of patients (P = .14).

Surgery was performed in 114 patients in the neoadjuvant chemoradiotherapy group and 108 patients in the neoadjuvant chemotherapy group. Postoperative morbidity occurred in 47.4% vs 42.6% of patients (difference = 4.8%, 95% confidence interval [CI] = −8.2% to 17.5%, P = .48). Anastomotic leak occurred in 9.6% vs 11.1% of patients (difference = –1.5%, 95% CI = −6.8% to 9.9%, P = .72). Complications of Clavien-Dindo classification IIIb or higher occurred in 11.4% vs 10.2% (difference = 1.2%, 95% CI = −7.3% to 9.6%, P = .77). Death occurred within 90 days in four patients (3.5%) vs three patients (2.8%; P = .94).


  • Postoperative complications and mortality were similar in the neoadjuvant chemoradiotherapy vs neoadjuvant chemotherapy groups.
  • The pathologic complete response rate was higher with neoadjuvant chemoradiotherapy.

Pathologic Complete Response and Early Survival

R0 resection was achieved in 97.3% of the neoadjuvant chemoradiotherapy group vs 96.2% of the neoadjuvant chemotherapy group (P = .92). Pathologic complete response was achieved in 35.7% vs 3.8% (P < .001), with a higher rate of negative lymph nodes (66.1% vs 46.2%, P = .03) in the neoadjuvant chemoradiotherapy group.

On intention-to-treat analysis, 1-year overall survival was 87.1% in the neoadjuvant chemoradiotherapy group vs 82.6% in the neoadjuvant chemotherapy group (P = .30), with the neoadjuvant chemoradiotherapy group having a reduced rate of death due to tumor progression or disease recurrence (6.8% vs 14.4%, P = .046). Death due to tumor-unrelated causes was similar in the two groups (6.1% vs 3.0%, P = .24).

The investigators concluded, “Initial results of the trial showed that neoadjuvant chemoradiotherapy followed by minimally invasive esophagectomy has similar safety to and better histopathologic outcome than neoadjuvant chemotherapy followed by minimally invasive esophagectomy for treatment of locally advanced esophageal squamous cell carcinoma.”

Lijie Tan, MD, of the Department of Thoracic Surgery, Zhongshan Hospital, Fudan University, Shanghai, is the corresponding author for the JAMA Surgery article.

Disclosure: The study was supported by the Foundation of Science and Technology Commission of Shanghai Municipality, Clinical Research Foundation of Zhongshan Hospital, and Clinical Science & Technology Innovation Project of Shanghai Shenkang Hospital Development Center. For full disclosures of the study authors, visit

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