Protocol for a phase II interventional trial investigating indocyanine green (ICG) fluorescence guided lymph node mapping for determination of bowel resection margins in colon cancer (ISCAPE)

Background: Optimal extent of lymph node dissection for colon cancer is debatable. Extensive lymphadenectomy may increase complication rate, while limited lymph node dissection may compromise oncological outcome. One of promising ways to find balance is to tailor extent of lymph node dissection to patient's individual anatomy using ICG lymphatic mapping. Methods: This is a single center interventional phase II trial with single group assignment aiming to determine if ICG lymphatic mapping sensitivity is sufficient to guide resection margins selection in colon cancer surgery. The trial's primary endpoint is proportion of pN+ patients in which affected lymph nodes are detected only within margins of ICG spread. Sample size of 101 patients was calculated using Buderer method [19] with a confidence level (1-alpha) of 0.95 as a minimum of cases required to test accuracy of lCG lymphatic mapping for estimated sensitivity of 0.99 and precision of 0.03. The average of pN+ cases in our center (42%) was used as prevalence. Secondary endpoints are incidence of adverse events related to ICG lymphatic mapping, feasibility of ICG lymphatic mapping for colon cancer, incidence of lymph node metastases outside conventional resection margins (10 cm), colon cancer lymphatic spread patterns, proportion of operations which extent is affected by ICG lymphatic mapping. The trial is conducted among female or male patients, 18 years or older, with signed informed consent, and diagnosed primary colon cancer. Inclusion criteria include pathologically confirmed adenocarcinoma of the colon, T1-4aN0-2bM0-1b, clinical indications to colonic resection, ECOG-0-2. Exclusion criteria consist of acute bowel obstruction, bleeding or perforation, adjacent organ invasion or peritoneal carcinomatosis, and contraindications to ICG administration. Eligible patients are allocated for colonic resection with intraoperative ICG mapping. During pathological examination, lymph nodes are assessed for presence of metastases and location in relation to tumor and fluorescence margins. The study began on 26 July 2022 and is conducted in and financed by N.N. Petrov NMRC of Oncology in Saint Petersburg, Russia, it is conducted in. Results: If after 101 ICG lymphatic mapping procedures, sensitivity of >96% is observed, this will provide rationale behind tailoring resection margins to fit ICG spread. Conclusions: ICG lymphangiography allows a surgeon to see locoregional lymphatics of a tumor site in real time and tailor colon and mesentery resection margins to meet oncological and functional needs. More data is needed to make this approach more widespread.