Fluorescence-guided versus non-fluorescence-guided resection in high-grade glioma: a systematic review and meta-analysis of survival outcomes

Fluorescence-guided resection (FGR) in high-grade glioma surgeries improves tumor visualization and resection extent. Although resection completeness is well documented, its impact on survival varies across studies due to confounding factors and heterogeneity. We conducted a systematic review and meta-analysis to clarify the relationship between fluorescence guidance and survival, distinguishing unadjusted from adjusted effects. A systematic search of PubMed, Embase, Scopus, and Web of Science found studies comparing FGR and non-FGR in adult high-grade glioma patients. Overall survival (OS) and progression-free survival (PFS) were analyzed separately. Risk of Bias was assessed with ROBINS-I and RoB 2, and evidence certainty with GRADE. Seventeen studies involving a total of 2,937 patients (1,466 who underwent FGR and 1,471 who underwent non-FGR) met the inclusion criteria. In unadjusted analyses, FGR was associated with a statistically significant improvement in overall survival (HR 0.72, 95% CI [0.57–0.91]; I2 47.2%), compared to non-FGR. However, in analyses adjusted for key prognostic variables, this association was diminished and no longer reached statistical significance (aHR 0.63, 95% CI [0.30–1.30]; I2 80.3%). Progression-free survival analyses indicated trends toward benefit, although these were not statistically significant in both unadjusted (HR 0.70, 95% CI [0.26–1.89]; I2 = 57.9%) and adjusted models (aHR 0.86, 95% CI [0.29–2.54]; I2 = 80.3%), with notable heterogeneity observed. Subgroup analyses comparing 5-ALA and white-light surgery yielded similar patterns, with effects attenuated following adjustment. The certainty of evidence ranged from low to very low. FGR initially demonstrated superior survival outcomes in high-grade glioma; however, the significance diminished upon adjustment for confounders. It primarily serves as an adjunct to surgical procedures to facilitate safe and maximal resection rather than directly enhancing survival. Further randomized investigations incorporating molecular stratification are essential to elucidate its influence on long-term survival.