In a Dutch study reported in the Journal of Clinical Oncology, Markar et al found that routine use of minimally invasive vs open esophagectomy for esophageal cancer was associated with increased risk of pulmonary complications and other adverse outcomes, contrary to the findings of the clinical trial that resulted in widespread implementation of the minimally invasive approach in the Netherlands.
As stated by the authors, the 2012 publication of the multicenter, randomized, open-label Dutch TIME trial—which showed reduced rates of pulmonary infection with minimally invasive esophagectomy vs open esophagectomy—led to widespread uptake of the approach in the Netherlands and elsewhere in Europe. The aim of the current analysis was to determine whether TIME trial findings were replicated in routine practice in the Netherlands.
“When adopted nationally outside the TIME trial, minimally invasive esophagectomy was associated with an increase in total and pulmonary complications and reoperation rate. This may reflect nonexpert surgeons outside of high-volume centers performing this minimally invasive technique in a nonstandardized fashion outside of a controlled environment.”— Markar et al
Tweet this quote
Study Details
The study involved data from patients in the Dutch Upper GI Cancer Audit (DUCA) for transthoracic esophagectomy, with operations occurring between 2011 and 2017, and patients from the TIME trial, with operations occurring between 2010 and 2012. The TIME dataset included 115 patients, consisting of 59 who received minimally invasive esophagectomy and 56 who received open esophagectomy. The DUCA dataset included 4,605 patients, consisting of 2,652 who received minimally invasive esophagectomy and 1,953 who received an open procedure.
Key Findings
On univariate analysis in the TIME population, minimally invasive esophagectomy was associated with significant reductions in pulmonary complications (odds ratio [OR] = 0.23, 95% confidence interval [CI] = 0.09–0.56), pneumonia (OR = 0.26, 95% CI = 0.10–0.69), and pulmonary embolus (OR = 0.1, 95% CI = 0.01–0.86), but a higher proportion of Clavien-Dindo grade ≥ 3 complications (OR = 4.13, 95% CI = 1.41–2.13).
On multivariate analysis in the DUCA population, minimally invasive esophagectomy was associated with increased total postoperative complications (OR = 1.38, 95% CI = 1.22–1.55), pulmonary complications (OR = 1.31, 95% CI = 1.1–1.49), pneumonia (OR = 3.53, 95% CI = 2.58–4.84), Clavien-Dindo grade ≥ 3 complications (OR = 5.13, 95% CI = 3.83–6.89), and reoperation rate (OR = 1.45, 95% CI = 1.22–1.73), but was also associated with reduced 30-day mortality (OR = 0.72, 95% CI = 0.53–0.97), increased rate of R0 resection (OR = 1.77, 95% CI = 1.36–2.29), and increased average lymph node harvest.
On multivariate analysis in the TIME population, minimally invasive esophagectomy was associated with significantly reduced pulmonary complications (OR = 0.19, 95% CI = 0.06–0.61), pneumonia (OR = 0.24, 95% CI = 0.08–0.71), and pulmonary embolus (OR = 0.06, 95% CI = 0.01–0.64) and significantly increased Clavien-Dindo grade ≥ 3 complications (OR = 8.67, 95% CI = 2.18–34.42).
On multivariate analysis in the DUCA population, minimally invasive esophagectomy was associated with significantly increased total postoperative complications (OR = 1.36, 95% CI = 1.19–1.57), pulmonary complications (OR = 1.50, 95% CI = 1.29–1.74), reoperation rate (OR = 1.74, 95% CI = 1.42–2.14), Clavien-Dindo grade ≥ 3 complications (OR = 1.63, 95% CI = 1.15–2.31), and hospital length of stay; minimally invasive esophagectomy was also associated with significantly increased average lymph node harvest.
Multivariate analysis in the combined TIME and DUCA populations showed that inclusion in the TIME trial was associated with significant reductions in reoperations (OR = 0.48, 95% CI =0.240.97), Clavien-Dindo grade > 1 complications (OR = 0.82, 95% CI = 0.75–0.89), hospital length of stay, R1/2 margins (OR = 0.39, 95% CI = 0.16–0.95) and a significant increase in total lymph nodes harvested. A subset analysis in the minimally invasive esophagectomy group showed that inclusion in TIME was associated with significant reductions in pulmonary complications (OR = 0.20, 95% CI = 0.09–0.47), reoperations (OR = 0.38, 95% CI = 0.15–0.94), and hospital length of stay.
The investigators concluded, “When adopted nationally outside the TIME trial, minimally invasive esophagectomy was associated with an increase in total and pulmonary complications and reoperation rate. This may reflect nonexpert surgeons outside of high-volume centers performing this minimally invasive technique in a nonstandardized fashion outside of a controlled environment.”
Mark I. van Berge Henegouwen, MD, PhD, of Amsterdam University Medical Centers, Cancer Center Amsterdam, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was funded by the National Institutes of Health Research. For full disclosures of the study authors, visit ascopubs.org.
