Thoracoscopic esophagectomy tied to better survival than open surgery for esophageal cancer

Thoracoscopic esophagectomy (TE) has demonstrated its noninferiority to open transthoracic esophagectomy (OE) for patients with thoracic esophageal cancer in a study presented at ASCO GI 2024.

Overall survival rate at 3 years was significantly greater among patients who underwent TE than those who received OE (82.0 percent vs 70.9 percent). [ASCO GI 2024, abstract 249]

“TE was shown to be a standard treatment for patients with clinical stage I‒III thoracic esophageal cancer,” said the investigators led by Hiroya Takeuchi from the Department of Surgery, Hamamatsu University School of Medicine, Hamamatsu, Shizuoka, Japan.

A minimally invasive esophagectomy for thoracic esophageal cancer, TE has gained popularity across the globe over the past decade. However, no large-scale, multicentre randomized controlled trial has yet compared the long-term survival between TE and conventional OE.

To address this, Takeuchi and colleagues conducted a phase III trial (JCOG1409) to confirm the noninferiority of TE to OE in terms of OS. They randomized 300 eligible patients with clinical stage I‒III, excluding T4, thoracic esophageal squamous cell carcinoma to undergo either TE (n=150) or OE (n=150) between May 2015 and June 2022.

OS was the primary endpoint, while secondary ones were relapse-free survival (RFS), adverse events, the proportion of patients achieving R0 resection, the proportion of patients needing conversion from TE to OE, the proportion of patients requiring reoperation, changes in postoperative respiratory dysfunction, and postoperative quality-of-life score.

Noninferiority was defined as an upper limit of the confidence interval (CI) for the hazard ratio (HR) not exceeding 1.44, the predefined noninferiority margin.

Early termination

The investigators performed a second planned interim analysis with 64 OS events in June 2023, with a median follow-up of 2.6 years (interquartile range, 1.4‒4.9). Three-year OS stood at 82.0 percent (95 percent CI, 73.8‒87.8) in the TE group and 70.9 percent (95 percent CI, 61.6‒78.4) in the OE group.

The trial was terminated early by the Data and Safety Monitoring Committee, which also recommended the publishing of results because TE already demonstrated its noninferiority to OE in terms of OS after adjusting for multiplicity (HR, 0.64, 98.8 percent CI, 0.34‒1.21; one-sided p-value for noninferiority=0.000726, 0.00616).

RFS at 3 years was also significantly better with TE than with OE (72.9 percent vs 61.9 percent; HR, 0.68, 95 percent CI, 0.46‒1.01). The proportion of patients achieving R0 resection was 95.3 percent in the TE group and 90.0 percent in the OE group. In addition, one patient who underwent TE required conversion from TE to OE intraoperatively.

The overall morbidity after surgery did not differ significantly between the two treatment groups, but the proportion of reoperation was nominally lower in the TE group than in the OE group (2.0 percent vs 4.1 percent). Furthermore, respiratory dysfunction proportion at 3 months postoperatively was markedly lower in the TE group than in the OE group.