FLARE Study – Fluorescence-guided Lymphadenectomy for augmented retrieval and Evaluation in Rectal Cancer surgery

Abstract Background: In patients with mid-to-lower rectal cancer undergoing neoadjuvant chemoradiotherapy (NACRT), lymph node (LN) retrieval is often suboptimal, affecting accurate staging and prognosis. Fluorescence-guided surgery (FGS) using Indocyanine Green (ICG) has emerged as a technique to enhance lymphatic mapping and identify aberrant lymph nodes (LNs) that may be missed while operating under conventional white light. Objective: To assess whether peri-tumoral tattooing with ICG and FGS alters the extent of lymphadenectomy and improves LN yield in rectal cancer patients post-NACRT. Methods: This investigator-initiated, quasi-experimental study utilized a prospectively maintained database from January 2023 to December 2024. Following 1:1 propensity score matching for eight variables (age, gender, BMI, tumor location, T-stage, N-stage, surgical procedure, and tattooing), 46 ICG-tattooed patients were compared to 46 controls. The primary outcome was the number of patients in whom FGS modified the extent of lymphadenectomy. Secondary outcomes included the number and positivity of aberrant LNs, and their size. Results: Median aberrant LNs identified was 2 per patient. The LN yield was significantly higher in the tattooed group (14 ± 3.7) than in the non-tattooed group (7 ± 3, P < 0.001). In 23 patients (50%), FGS altered the lymphadenectomy extent. Five aberrant nodes (10.87%) were malignant, located in stations 16B1, 16B2, and mesorectal sub-zones. The mean size of aberrant nodes was 4 ± 2 mm. Conclusion: Fluorescence-guided lymphadenectomy significantly improves LN yield and aids in detecting small, otherwise occult, aberrant lymph nodes. ICG-guided techniques should be considered an adjunct to standard rectal cancer surgery following NACRT to ensure optimal oncologic outcomes.