Indocyanine Green (ICG) Fluorescence vs. Tc-99m Lymphoscintigraphy: Optimizing Sentinel Lymph Node Detection in Cutaneous Melanoma-A Systematic Review and Meta-Analysis

: Background: Sentinel lymph node (SLN) biopsy has emerged as a cornerstone in melanoma staging, offering targeted evaluation of regional lymphatic spread and guiding therapeutic decision-making. Traditionally, SLN mapping relies on lymphoscintigraphy using technetium-99m (Tc-99m) radiocolloid, but in recent years, indocyanine green (ICG) fluorescence imaging has emerged as a promising alternative. The aim of this review is to evaluate the diagnostic accuracy of ICG-near-infrared (NIR) imaging compared to standard Tc-99m lymphoscintigraphy in SLN biopsy (SLNB). Methods: A systematic review and meta-analysis were conducted, including 12 studies. The primary outcome was the false-negative rate; secondary outcomes included the total number of sentinel lymph nodes (SLNs) identified by ICG-NIR imaging and Tc-99m lymphoscintigraphy, the number of metastatic SLNs detected by each method, and the number of patients with metastatic disease. The statistical analysis for dichotomous variables was performed using the "Odds Ratio" (O.R.) calculated with the Mantel-Haenszel method. For continuous variables, the analysis utilized the "Mean Difference" calculated by the inverse variance method. All data are presented with a 95% confidence interval (CI). Results: ICG was associated with a significantly higher number of SLNs identified compared to Tc-99m (O.R.: 0.41, 95% CI: 0.34-0.49; p < 0.00001), while no significant differences were found in the detection of metastatic nodes, either as a proportion of total SLNs (O.R.: 1.04, 95% CI: 0.86-1.25; p = 0.68) or relative to total positive nodes (O.R.: 0.36, 95% CI: 0.16-0.81; p = 0.01). No statistically significant differences between the two techniques were found in the detection of metastatic patients (OR: 0.80, 95% CI: 0.31-2.03, p = 0.33) and in the total number of false-negative patients missed (risk difference (RD): 0.03, 95% CI: -0.04 to 0.09, p = 0.93). Conclusions: While ICG identifies a higher number of SLNs compared to Tc-99m, its ability to detect metastatic involvement is comparable between the two modalities. No significant differences were observed in the proportion of metastatic SLNs, the total number of positive nodes detected, the number of metastatic patients identified, and the false-negative rate. Given its favorable profile, ICG could represent a reliable alternative or adjunct to Tc-99 in SLNB. However, prospective studies are warranted to validate its standalone diagnostic role.