Fusobacterium nucleatum and response to treatment in colon and rectal cancer: a systematic review

Fusobacterium nucleatum (Fn) has been implicated in the progression of colorectal cancer (CRC), immune modulation, and resistance to systemic therapies. However, its role as a predictive biomarker of treatment response remains unclear. We conducted a systematic review to evaluate the association between Fn and oncologic treatment outcomes in CRC.

This systematic review was performed according to the PRISMA 2020 guidelines and registered in PROSPERO (CRD420261327958). MEDLINE, Scopus, and CENTRAL were searched through March 2026. Eligible studies included adult CRC patients with Fn assessment performed before or during treatment and reporting treatment-related outcomes. Primary endpoints included pathological complete response (pCR), tumour regression grade (TRG), and objective response rate (ORR). Secondary endpoints included disease-free survival (DFS), relapse-free survival (RFS), progression-free survival (PFS), and overall survival (OS).

Eleven studies including 1571 patients, were analysed. In locally advanced rectal cancer, four of five studies indicated that higher pre-treatment Fn abundance was associated with poorer pathological response to neoadjuvant chemoradiotherapy. Persistent Fn positivity after treatment was linked to an increased relapse risk. In metastatic CRC receiving immunotherapy, two studies reported enrichment of Fn in non-responders, while one study observed improved outcomes in Fn-positive tumours treated with PD-L1 blockade. In chemotherapy-treated metastatic CRC, Fn abundance was significantly higher in patients with progressive disease. Overall, the quality of evidence was rated low to very low.

Fn appears to be associated with treatment resistance across multiple CRC settings and may represent a promising biomarker and therapeutic target. Prospective biomarker-driven studies are warranted.