Neoadjuvant Bevacizumab in Newly Diagnosed, Surgically Resectable Glioblastoma: A Systematic Review and Meta-Analysis of Survival and Functional Outcomes

  1. Farbod Tabasi Kakhki
  2. Fatemeh Sadat Hosseini Khajouei
  3. Aysan Valinejad qanati
  4. Maryam Babazadeh
  5. Roozbeh Tavanaei
  6. Melika Hajimohammadebrahim-Ketabforoush
  7. Sayeh Oveisi
  8. Saeed Oraee-Yazdani
  9. Alireza Zali
  10. Farzan Fahim
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Abstract

Background

Glioblastoma (GBM) remains one of the most aggressive primary brain tumors, with limited survival despite maximal safe resection and chemoradiotherapy. Neoadjuvant bevacizumab (BEV) has been proposed to reduce peritumoral edema, improve functional status, and potentially enhance progression-free survival (PFS). However, its survival benefit in newly diagnosed, surgically resectable GBM remains unclear.

Objective

To systematically review and quantitatively synthesize the evidence on neoadjuvant BEV in adult patients with newly diagnosed, resectable GBM, focusing on survival and functional outcomes.

Methods

Following PROSPERO registration (CRD420251078761), we searched PubMed, Embase, Scopus, Web of Science, and Cochrane Library up to July 20, 2025, without language restrictions. Eligible randomized trials, non-randomized trials, and cohort studies compared neoadjuvant BEV (alone or with other therapies) to standard care without BEV. Primary outcomes were overall survival (OS) and PFS; secondary outcomes included Karnofsky Performance Status (KPS), steroid use, radiological response, and biomarkers. Data were pooled using a random-effects model.

Results

Thirteen studies (2 RCTs, 7 non-randomized trials, 4 cohorts) met the inclusion criteria; four (n=751) were eligible for meta-analysis. Pooled HR for OS was 0.72 (95% CI: 0.42–1.25, p=0.246) and for PFS was 0.72 (95% CI: 0.42–1.22, p=0.220), both with low heterogeneity (I2=0%). Functional outcomes suggested improved KPS and reduced steroid dependence, but certainty was low. Biomarker and radiological findings were inconsistent.

Conclusions

Neoadjuvant BEV in resectable GBM does not significantly improve OS or PFS but may offer symptomatic and functional benefits. Current evidence is limited by small sample sizes, heterogeneous protocols, and low methodological quality. Well-designed multicenter RCTs are warranted.

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