Blood Perfusion Assessment by Indocyanine Green Fluorescence Imaging for Minimally Invasive Rectal Cancer Surgery (EssentiAL trial): A Randomized Clinical Trial

Abstract

Objective: The aim of the present randomized controlled trial was to evaluate the superiority of indocyanine green fluorescence imaging (ICG-FI) in reducing the rate of anastomotic leakage in minimally invasive rectal cancer surgery.

Background: The role of ICG-FI in anastomotic leakage in minimally invasive rectal cancer surgery is controversial according to the published literature.

Methods: This randomized, open-label, phase 3, trial was performed at 41 hospitals in Japan. Patients with clinically stage 0-III rectal carcinoma less than 12 cm from the anal verge, scheduled for minimally invasive sphincter-preserving surgery were preoperatively randomly assigned to receive a blood flow evaluation by ICG-FI (ICG+ group) or no blood flow evaluation by ICG-FI (ICG- group). The primary endpoint was the anastomotic leakage rate (grade A+B+C, expected reduction rate of 6%) analyzed in the modified intention-to-treat population.

Results: Between December 2018 and February 2021, a total of 850 patients were enrolled and randomized. After the exclusion of 11 patients, 839 were subject to the modified intention-to-treat population (422 in the ICG+ group and 417 in the ICG- group). The rate of anastomotic leakage (grade A+B+C) was significantly lower in the ICG+ group (7.6%) than in the ICG- group (11.8%) (relative risk, 0.645; 95% confidence interval 0.422-0.987; P =0.041). The rate of anastomotic leakage (grade B+C) was 4.7% in the ICG+ group and 8.2% in the ICG- group ( P =0.044), and the respective reoperation rates were 0.5% and 2.4% ( P =0.021).

Conclusions: Although the actual reduction rate of anastomotic leakage in the ICG+ group was lower than the expected reduction rate and ICG-FI was not superior to white light, ICG-FI significantly reduced the anastomotic leakage rate by 4.2%.

FIGURE 1

Trial profile. mITT indicates modified intention-to-treat.

FIGURE 2

Subgroup analyses of the effect of ICG+ vs ICG− group on anastomotic leakage. To determine for which subjects a blood flow evaluation would be useful in an exploratory manner, a logistic regression analysis was conducted for each subgroup as a post hoc analysis, and forest plots of the odds ratio (OR) and their 95% confidence intervals (CIs) for the allocation arm were created. Subgroup analyses were performed for age (<70 vs ≥70 yr old), sex (male vs female), body mass index (<25 vs ≥25 kg/m²), albumin (Alb;<4 vs ≥4), clinical stage (0-I vs II vs III), tumor height from the anal verge (<5 vs ≥5 cm), maximum tumor diameter (<5 vs ≥5 cm), approach (laparoscopic surgery vs taTME vs robotic surgery), diverting stoma (absence vs presence), preservation of the left colon artery (no preservation vs preservation), and neoadjuvant chemoradiotherapy (no chemoradiotherapy vs chemoradiotherapy). ICG indicates indocyanine green; taTME, transanal total rectal resection.