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While surgery using 5-aminolevulinic acid improves total resection rates in high-grade glioma, the best outcomes are seen with multifaceted surgical approaches.

“Despite advances in surgical methods, chemotherapy, and radiotherapy, the overall survival of patients with high-grade gliomas remains poor, with a median survival of approximately 15 months for glioblastoma and slightly longer for other high-grade glioma subtypes,” researchers wrote in Cancers. “Maximizing the extent of tumor resection is a crucial factor in enhancing survival outcomes, yet complete tumor removal is challenging due to the infiltrative nature of these tumors and the difficulty in differentiating malignant tissue from healthy brain parenchyma under standard white-light visualization.”

The introduction of fluorescence-guided surgery using 5-aminolevulinic acid (5-ALA) has improved a surgeon’s ability to visualize and resect malignant tissues more accurately, but comparative data assessing patients who received 5-ALA-assisted surgery versus conventional resection without 5-ALA remain limited.

The researchers retrospectively assessed 141 patients with high-grade gliomas (HGGs) who underwent 5-ALA-guided (n=71) or conventional white-light (n=70) resection. They used propensity score matching and multivariate Cox regression models to examine the impact of 5-ALA on surgical outcomes and survival.

Gross Total Resection Improves With 5-ALA

Use of gross total resection was much more common in the 5-ALA group than the conventional white-light group (28.17% vs 12.86%; P=0.0245). There was no statistically significant difference in overall survival between groups after matching, but patients who had gross total resection had significantly better survival compared with those with subtotal resection (log-rank P=0.0423).

Multivariate Cox regression identified the following as independent predictors of better survival:

• Radiotherapy: HR=0.291 [95% CI, 0.166–0.513]; P<0.001)
• Higher Karnofsky performance status (HR=0.962 [95% CI, 0.942–0.982]; P=0.0003)
  • Gross total resection (HR=0.476 [95% CI, 0.272–0.834]; P=0.0091)

However, the use of 5-ALA was not an independent predictor of better survival.

Regarding other treatments, radiotherapy (P=0.04) and chemotherapy (P=0.0085) were more often used in the conventional white-light group.

Greatest Benefit Seen With Use of Multiple Tools

The findings indicate that 5-ALA fluorescence-guided surgery significantly improves the rates of gross total resection but does not independently improve overall survival when adjusting for confounders in propensity score matching.

“Improved outcomes increasingly depend on the synergistic use of adjunct technologies,” the researchers wrote. “Tools like 5-ALA fluorescence enable more aggressive resections while helping preserve function, but their full benefit emerges only when integrated with complementary strategies. For example, combining 5-ALA with intraoperative mapping led to [gross total resection] in 96% of cases and significantly prolonged survival.”

Molecular profiling, including identifying isocitrate dehydrogenase mutations, MGMT methylation, and EGFR amplification, can refine surgical decision-making even further, augmenting patient selection for use of these tools and guiding postoperative therapy.

“Even with MRI-confirmed [gross total resection], residual intraoperative fluorescence has been shown to predict poorer outcomes, suggesting that 5-ALA may highlight infiltrative tumor cells beyond what imaging can detect,” the researchers noted. “This underlines the importance of multimodal integration—not just surgical but molecular, functional, and imaging-guided techniques—to address the inherently diffuse nature of high-grade gliomas.”

Thus, they continued, no single modality is sufficient, but with combined use, the techniques outlined have the potential to improve outcomes in high-grade glioma.

“While our findings confirm previously established evidence that gross total resection is a key prognostic factor in [high-grade glioma] management, the value of our study lies in real-world verification within a resource-limited healthcare system,” the study team wrote. “Specifically, we demonstrate that even with limited access to intraoperative mapping, molecular profiling, and advanced adjuvant protocols, 5-ALA significantly facilitates [gross total resection] in daily practice. This reinforces its value not only in high-resource centers but also in settings with infrastructural constraints.”