Fluorescence-guided Surgery in Glioblastoma: 5-ALA, SF or Both? Lessons Learned from 700 Consecutive Cases

Introduction: Extent of resection (EOR) is a key prognostic factor, closely linked to progression-free survival (PFS) and overall survival (OS). Over two decades, fluorescence-guided surgery (FGS) with 5-aminolevulinic acid (5-ALA) and sodium fluorescein (SF) has supported glioma surgeries to achieve maximal EOR. There is no clear advantage of one fluorophore over the other for EOR volumes, and debate continues over specific applications and associated costs.

Methods: We retrospectively analyzed high-grade glioma resections at the Neurosurgery Unit of AOU Città della Salute e della Scienza di Torino, categorizing patients by 5-ALA, fluorescein, or both. Primary outcomes included EOR, OS, and PFS; secondary measures included surgery duration and postoperative neurological deficits.

Results: 700 patients were included in our analysis. 228 patients received only 5-ALA, 134 patients received both 5-ALA and fluorescein, and 338 patients received only fluorescein. Mean PFS and OS were 8.59 and 16.9 months, respectively.There were no differences observed in EOR of the enhancing volume when using 5-ALA versus fluorescein alone, but superiority of dual fluorescence was noted in FLAIR volume resection, without impacting postoperative neurological deficits. Additionally, average surgery duration was shorter with combined fluorescein and 5-ALA (208 minutes) compared to 5-ALA alone (242 minutes). In order to maximize the advantages of the two methods and, at the same time, curb their limitations, we propose to use them simultaneously but in sequential fashion. Therefore, the first debulking phase is achieved by using fluorescein alone, followed by a second look using 5-ALA

Conclusion : Fluorophores in glioblastomas are highly reliable, with dual fluorescence particularly increasing EOR of the tumor volume without assuming MDC, with the advantage of using fluorescein for the enhancing part and refining the resection with 5-ALA for the infiltrating part, thereby reducing surgical times. Preoperative selection of cases that can benefit from dual fluorescence allows for resource optimization.