# Two-Stage Surgery in Patients with Diffuse Glioma—Indications, Implications and Outcome

## TL;DR

Two-stage surgery for brain tumors in sensitive areas can safely increase tumor removal without worsening patient function.

## Contribution

Demonstrates the feasibility of two-stage surgery in achieving maximal resection for diffuse gliomas in eloquent brain regions.

## Key findings

- Second surgery significantly reduced residual tumor volume without functional or neurological decline.
- Two-stage surgery achieved maximal or supramaximal resection in 58.88% of cases.
- Complication rates were notable but did not outweigh the benefits in selected patients.

## Abstract

Maximal safe tumour resection is a key prognostic factor in patients with diffuse gliomas, but complete resection is often limited by tumour location in eloquent brain areas. In this retrospective single-centre study, we analysed outcomes of patients undergoing a planned two-stage surgical approach for diffuse gliomas. Two-stage surgery was mainly used for eloquent or multifocal tumours, non-compliance during awake surgery, or as a primary debulking strategy. The second surgery significantly reduced residual tumour volume and increased rates of maximal or supramaximal resection without relevant deterioration of neurological or functional status. Although complication rates were not negligible, planned two-stage surgery appears to be a feasible strategy in selected patients to extend the extent of resection while preserving neurological function.

Introduction: Significant studies have substantiated the evidence for complete resection of intrinsic brain tumours in recent years. However, achieving this through a single surgery is not always possible due to tumour localisation in eloquent areas. Therefore, the present analysis aimed to evaluate surgical outcomes in a cohort of patients undergoing planned two-stage glioma surgery. Methods: Patients who underwent surgery for diffusely infiltrating brain tumours between 2013 and 2023 at the Department of Neurosurgery at Düsseldorf University Hospital were screened for undergoing two-stage surgery, defined by a priori-considered surgical re-intervention up to 6 weeks after the initial surgery. Results: Of 1558 patients with glioma, 447 underwent multiple surgeries, of whom 36 underwent planned two-stage surgery during the course of their disease. Two-stage surgery was performed mostly as glioma surgery at first diagnosis (75%). The mean time between the first and second surgery was 11.67 days (±7.59). Two-stage surgery was performed due to various reasons, mostly in localisations that required multifocal approaches (47.2%), due to non-compliance during initial awake surgery (30.6%), or cases with primary debulking for subsequent awake-surgery approaches (22.2%). Tumours were mainly located in the left hemisphere (50%) (right hemisphere 25%, or bilateral 25%) and motor- or speech-eloquent in 61.11%. Tumours were 72.2% IDH-wildtype. An intended complete resection result was achieved in 58.88% after the second surgery, changing from 93.94% submaximal resection to 58.88% supramaximal and maximal resection after the second surgery. Second surgery significantly reduced residual tumour volume of both T1-CE (Wilcoxon signed-rank test, Z = −4.62, p < 0.001) and T2-nCE (Z = −4.62, p < 0.001). In contrast, functional (KPS: Z = −0.93, p = 0.350) and neurological status (NIHSS: Z = −0.89, p = 0.372) did not significantly change. Perioperative complications of the second surgery occurred in nine (25%) cases, requiring surgical intervention under general anaesthesia or ICU treatment (Clavien–Dindo grade IIIb/IV) in six (16.67%) cases. Conclusion: Planned two-stage surgery was mostly performed as a surgical strategy in eloquent locations to achieve supramaximal or maximal resection. A two-staged surgery significantly extended resection results without neurological and functional deterioration. Despite relevant complication rates, primary debulking followed by staged resection as well as two-staged multifocal approaches may yield a favourable risk–benefit profile.