Thoracoscopic esophagectomy noninferior to open surgery in thoracic esophageal cancer

medwireNews: Thoracoscopic esophagectomy is noninferior to open esophagectomy in terms of long-term survival in patients with resectable thoracic esophageal cancer, the MONET trial suggests.

While thoracoscopic esophagectomy has been established as the standard of care for patients with stage I–III esophageal cancer, with short-term benefits, there has been no large-scale trial comparison with open surgery in terms of long-term survival, write Hiroya Takeuchi (Hamamatsu University School of Medicine, Japan) and colleagues in The Lancet Gastroenterology & Hepatology.

The open-label phase 3 trial enrolled 300 adult patients with a median age of 68 years and 82% being men. Almost all (99%) had histologically confirmed esophageal squamous cell carcinoma, which was commonly located (52%) in the middle thoracic esophagus. The cancer was most often local with a clinical N stage of 0 (52%).

These patients had an ECOG performance status of 0 (96%) or 1 (4%); clinical stage I, II, or III disease, but not T4 stage; and had not received treatment for esophageal cancer, except for resection of superficial lesions and preoperative chemotherapy (60%).

The patients were randomly assigned to receive right open transthoracic esophagectomy (n=150) or right thoracoscopic esophagectomy (n=148), with procedures including at least D2 lymphadenectomy.

Survival outcomes

Thoracoscopic esophagectomy was classed as noninferior to open transthoracic esophagectomy if the primary endpoint of overall survival (OS) was within a 9% margin at 3 years, and a hazard ratio (HR) of 1.44 in favour of open surgery.

At the first interim analysis, at a median follow-up of 1.6 years, thoracoscopic esophagectomy showed a higher OS than open surgery, with a HR of 0.56, but the p value for noninferiority was not reached.

However, noninferiority was established at the second interim analysis after a median follow-up of 2.6 years. Thoracoscopic esophagectomy showed a 3-year OS rate of 82.0% versus 70.9% with open surgery, giving a significant HR of 0.64. The trial was then terminated after meeting the prespecified goal of noninferiority of thoracoscopic esophagectomy.

While thoracoscopic esophagectomy showed higher 3-year relapse-free survival than open surgery, with respective rates of 72.9% versus 61.9%, the difference was not statistically significant.

And in an updated analysis at 3.0 median years of follow-up, there was no significant difference between the groups in terms of overall and relapse-free survival.

In subgroup analysis after the second interim analysis, patients with clinical N stages of 1–3 saw an especially strong benefit in overall and relapse-free survival from thoracoscopic esophagectomy relative to open surgery, with corresponding HRs of 0.53 and 0.51.

Surgical complications and other outcomes

Takeuchi et al report that the thoracoscopic group saw significantly less blood loss than the open group (171 vs 250 mL) but there was no significant difference in median operation time, R0 resection rate, and duration of hospital stay.

There was also a significantly smaller decline in respiratory function in the thoracoscopic group at 3 months, but not at 1 year, which they suggest was “due to reduced surgical trauma to the thoracic wall and less manipulation of the right lung.”

However, there was no significant difference between the groups 1 or 3 months after surgery in terms of quality of life, “possibly due to recent advancements in perioperative management and enhancement of outpatient care in the past 10 years,” the investigators write.

The treatment groups had comparable rates of grade 3 and more severe intraoperative complications (1 vs 1%), all of which were intraoperative bleeding, and postoperative complications before first discharge (42 vs 44%). There was a nonsignificant trend towards fewer grade 4 adverse events with thoracoscopic esophagectomy.

Thoracoscopic esophagectomy was also associated with a significantly lower rate of postoperative bleeding, as well as a nonsignificant trend towards reduced incidences of grade 3 or more severe pneumonia and pleural effusion compared with open surgery, but also a nonsignificantly increased risk of grade 3 anastomotic leakage.

Four treatment-related deaths occurred in the thoracoscopic group (three deaths from aspiration pneumonia and one from suspected suffocating) and two in the open group (one postoperative bleeding and one suspected aspiration pneumonia).

The authors acknowledge limitations to the study, including the low number of events for calculating OS, and the challenge to recruit patients as “people did not want to have an open surgery, given that thoracoscopic esophagectomy is widely accepted.”

With the rising popularity of robot-assisted minimally invasive esophagectomy, which “offers precise instrument handling with multi-jointed functions that enable tremor-free, delicate movements,” Takeuchi  and co-authors say that they look forward to comparative trials of robotic surgery with thoracoscopic esophagectomy..

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The Lancet Gastroenterology & Hepatology 2025; doi: 10.1016/S2468-1253(25)00207-9