Intratumoral Fusobacterium species and survival in resectable colorectal cancer: a multicenter cohort study.

BACKGROUND

Despite standard-of-care treatment, a substantial proportion of patients with resectable colorectal cancer (CRC) relapse. We investigated the impact of surgical and postsurgical Fusobacterium spp. detection as a prognostic biomarker in stage I to III CRC from a national multicenter ambispective observational study.

PATIENTS AND

METHODS

Patients with stage I to III CRC were enrolled at nine referral centers. Intratumoral Fusobacterium spp. was centrally detected using RNA in situ hybridization in surgical tumor samples. Correlations were analyzed between intratumoral Fusobacterium spp. and outcomes [recurrence-free survival (RFS), disease-free survival (DFS), CRC-specific survival (CRC-SS), and overall survival (OS)]. As an exploratory aim, Fusobacteriumnucleatum clearance in stool at follow-up using quantitative PCR was investigated.

RESULTS

Among 740 assessable patients (median age 61 years; 63% men), 21% had detectable intratumoral Fusobacterium spp. (classified as Fusobacterium-positive tumors). Fusobacterium spp. positivity was more common in right-sided, high-grade tumors with venous, lymphatic, and perineural invasion (VELIPI) and was associated with reduced immune infiltration. At a median follow-up of 48.6 months, Fusobacterium spp. positivity was independently associated with shorter RFS [hazard ratio (HR) 1.87, 95% confidence interval (CI) 1.23-2.84, P = 0.003] and DFS (HR 1.84, 95% CI 1.27-2.70, P = 0.001) but not with CRC-SS (HR 1.39, 95% CI 0.72-2.70, P = 0.321) or OS (HR 1.51, 95% CI 0.91-2.50, P = 0.113) in fully adjusted multivariate models. Adjuvant chemotherapy (ACT) significantly improved DFS in Fusobacterium-negative patients (HR 0.38, 95% CI 0.20-0.74, P = 0.004), but not in Fusobacterium-positive patients (HR 0.68, 95% CI 0.25-1.8, P = 0.44). Post-operative Fusobacteriumnucleatum positivity in stool during follow-up was detectable up to 3 years before recurrence and associated with an increased risk of relapse (odds ratio 61.0, 95% CI 2.3-1652, P = 0.01).

CONCLUSIONS

The presence of Fusobacterium spp. identifies a subset of patients with CRC with aggressive biology, immune suppression, and reduced benefit to ACT. Testing for Fusobacterium spp. in tumors and stool may support precision oncology approaches to guide treatment decision making and post-operative surveillance strategies.