Implementation of Minimally Invasive Esophagectomy From a Randomized Controlled Trial Setting to National Practice

Abstract

Purpose: The aim of this study was to examine the external validity of the randomized TIME trial, when minimally invasive esophagectomy (MIE) was implemented nationally in the Netherlands, using data from the Dutch Upper GI Cancer Audit (DUCA) for transthoracic esophagectomy.

Methods: Original patient data from the TIME trial were extracted along with data from the DUCA dataset (2011-2017). Multivariate analysis, with adjustment for patient factors, tumor factors, and year of surgery, was performed for the effect of MIE versus open esophagectomy on clinical outcomes.

Results: One hundred fifteen patients from the TIME trial (59 MIE v 56 open) and 4,605 patients from the DUCA dataset (2,652 MIE v 1,953 open) were included. In the TIME trial, univariate analysis showed that MIE reduced pulmonary complications and length of hospital stay. On the contrary, in the DUCA dataset, MIE was associated with increased total and pulmonary complications and reoperations; however, benefits included increased proportion of R0 margin and lymph nodes harvested, and reduced 30-day mortality. Multivariate analysis from the TIME trial showed that MIE reduced pulmonary complications (odds ratio [OR], 0.19; 95% CI, 0.06 to 0.61). In the DUCA dataset, MIE was associated with increased total complications (OR, 1.36; 95% CI, 1.19 to 1.57), pulmonary complications (OR, 1.50; 95% CI, 1.29 to 1.74), reoperations (OR, 1.74; 95% CI, 1.42 to 2.14), and length of hospital stay. Multivariate analysis of the combined and MIE datasets showed that inclusion in the TIME trial was associated with a reduction in reoperations, Clavien-Dindo grade > 1 complications, and length of hospital stay.

Conclusion: When adopted nationally outside the TIME trial, MIE 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.

FIG 1.

Graph showing a decrease in average rate of reoperation (broken line with circles at the bottom) from minimally invasive esophagectomy (MIE) and no change in postoperative complications (lines with triangles at the top) from open and MIE over the study period within the Dutch Upper GI Cancer Audit dataset.

FIG 2.

Odds ratios from multivariate analysis of the effect of minimally invasive esophagectomy (MIE) on key clinical outcomes in Dutch Upper GI Cancer Audit (DUCA) and TIME data. LoS, length of hospital stay. Open group was used as reference value for comparison with MIE group.

FIG A1.

Odds ratios from univariate comparison of patient demographics and tumor factors from the TIME and Dutch Upper GI Cancer Audit (DUCA) datasets. Open group was used as reference value for comparison with minimally invasive esophagectomy group. ASA, American Society of Anesthesiologists; BMI, body mass index.

FIG A2.

Odds ratios from univariate comparison of clinical and pathologic outcomes from TIME and Dutch Upper GI Cancer Audit (DUCA) datasets. Open group was used as reference value for comparison with minimally invasive esophagectomy group.

FIG A3.

Odds ratios for multivariate analysis of the effect of inclusion in the TIME trial or Dutch Upper GI Cancer Audit (DUCA) on key clinical outcomes. DUCA group was used as reference value for comparison with TIME group. MIE, minimally invasive esophagectomy. LoS, length of hospital stay.