Background:
Anastomotic leak is the most feared complication of rectal cancer surgery, being reported in 10–15% of patients. Indocyanine green near-infrared angiography has been introduced to evaluate anastomotic blood supply and reduce anastomotic leak, with promising results.
Objective and main outcome measure:
The primary objective was to evaluate the efficacy and mechanism of indocyanine green near infrared angiography in reducing the anastomotic leak rate in rectal cancer surgery. The primary end point was clinical anastomotic leak rate within 90 days of operation. The key secondary end point was the rate of all anastomotic leaks within 90 days of operation.
Design and methods:
A prospective, unblinded, parallel-group, non-Clinical Trial of an Investigational Medicinal Product, randomised controlled trial comparing surgery with indocyanine green near infrared angiography against standard care (white light laparoscopy) to determine the effect on anastomotic leak in patients undergoing elective rectal cancer resection. Participants were randomised 1 : 1 using minimisation with a random element. Analyses were intention-to-treat.
Setting:
Twenty-eight European hospitals.
Participants:
Adult patients ≥ 18 years with a diagnosis of rectal cancer, suitable for curative resection by high or low anterior resection with anastomosis.
Interventions:
Surgery with indocyanine green near infrared angiography or standard of care.
Results:
Between 10 January 2018 and 15 August 2023, 766 participants were randomised; 698 (91.1%) participants were included in the primary analysis. The overall rates of clinical and all anastomotic leaks were 90/698 (12.9%) and 121/698 (17.3%), respectively. In the primary analysis, clinical anastomotic leaks occurred in 36/343 (10.5%) and 54/355 (15.2%) in the indocyanine green near-infrared angiography and standard care groups, respectively; the primary model estimated an adjusted odds ratio of 0.667 (95% confidence interval 0.419 to 1.060; p = 0.0868). Key secondary analysis, including all anastomotic leaks, observed 47/343 (13.7%) and 74/355 (20.8%) leaks in indocyanine green near-infrared angiography and standard care groups, respectively, with the key secondary model estimated an adjusted odds ratio of 0.607 (95% confidence interval 0.403 to 0.915; p = 0.0172) in favour of indocyanine green near infrared. In the economic analysis, indocyanine green near infrared angiography had a 62% chance of being cost-effective and led to a per-patient cost saving of £97.34 (95% confidence interval £91.32 to £103.00).
Limitations:
Surgeons or data collectors were unable to be blinded. The trial population largely consisted of White ethnic groups, and so some ethnic groups are likely under-represented.
Conclusions:
The use of indocyanine green near infrared angiography reduces the rate of clinical and all anastomotic leaks following rectal cancer resection, but only reached statistical significance for all leaks. It is safe, easy to use and cost-effective. Taken in context with other clinical trials, our results suggest that indocyanine green near infrared angiography should be considered as the future standard of care in rectal cancer surgery.
Future work:
The microbiome substudy has shown important shifts in the microbiome profile across the rectal cancer treatment pathway that warrant further investigation regarding a causal role in anastomotic leak and other postoperative complications.
Further work is required to standardise and quantify indocyanine green near infrared angiography as a means of real-time assessment of tissue perfusion.
Funding:
This synopsis presents independent research funded by the National Institute for Health and Care Research (NIHR) Efficacy and Mechanism Evaluation programme as award number 14/150/62.
CORE (COnnecting REpositories)
CORE (COnnecting REpositories)