Long-Term Oncological Outcomes of Granulocyte Colony-Stimulating Factor (G-CSF) Treatment in Gastrointestinal Cancers: A Systematic Review and Meta-Analysis

Background: Granulocyte-colony stimulating factor (G-CSF) prophylaxis is widely used in gastrointestinal (GI) cancers. The use of G-CSF in GI cancers has not previously been investigated systematically in a meta-analysis. Thus, we systematically reviewed the literature to describe the G-CSF use and potential influence on long-term oncological outcomes in GI cancers. Method: The literature search of this systematic review and meta-analysis was conducted in PubMed, Embase, Cochrane Library and Web of Science. The PRISMA-P guidelines were followed. Studies that reported data on patients with GI cancers undergoing oncological treatment with G-CSF prophylaxis were included. Outcomes of interest were overall survival (OS), progression-free survival (PFS) and adverse events (AE), specifically neutropenia grade III/IV. A time-to-event random-effects meta-analysis was conducted. Risk of bias was assessed using the Newcastle–Ottawa Scale and the Cochrane Risk of Bias Tool for Randomized Controlled Trials (RoB) tool. Findings: In total, 2452 articles were screened for eligibility. Ultimately, 13 studies were included with a total patient number of 2673. The included studies indicated a positive association between OS and G-CSF prophylaxis (HR 0.72, 95% CI: 0.56–0.91, I2: 54%, low quality evidence). No significant relation between G-CSF use and PFS was found in the pooled analyses (HR 0.74, 95% CI: 0.51–1.08, I2: 73%, moderate quality evidence). However, a positive effect of G-CSF use was found in the retrospective cohorts reporting data on PFS (HR 0.50, 95% CI: 0.32–0.77, I2: 0%). A marked drop in neutropenia grade III/IV rates was observed in patients treated with G-CSF (risk ratio (RR) 0.46, 95% CI: 0.28–0.77, I2: 72%, high quality evidence). Interpretation: G-CSF prophylaxis provides a reduction in neutropenia grade III/IV in patients with GI cancers (high level of certainty) and a favorable OS (low certainty), while PFS is unaffected (moderate certainty). Studies on PFS and G-CSF use are nonetheless limited.
Keywords: G-CSF; filgrastim; peg-filgrastim; gastrointestinal cancer; survival; adverse events