When intratumoral Fusobacterium is found in surgical samples of colorectal cancer, the disease is typically more aggressive, with a weaker immune response and limited efficacy for adjuvant chemotherapy, making the cancer more likely to recur, according to findings from the multicenter FUSOMAP project published in ESMO Open. Going forward, the researchers believe that Fusobacterium could be used as a prognostic and predictive biomarker in patients with resectable colorectal cancer.
“[T]hese results suggest that Fusobacterium could be a powerful tool and biomarker for personalizing colorectal cancer treatment. Its detection could help identify patients with a poorer prognosis who might derive less benefit from chemotherapy, as well as anticipate possible relapse,” stated corresponding study author Paolo Nuciforo, MD, PhD, Head of Vall d'Hebron Institute of Oncology's (VHIO) Molecular Oncology Group and Principal Investigator of the FUSOMAP study. “This could help guide more personalized treatment decision-making and facilitate the implementation of the most appropriate surveillance strategies.”
Background
FUSOMAP is a 3-year multicenter project including a major observational study across nine Spanish hospital focused on developing microbiota-based diagnostic and prognostic models. It is considered the largest European study of microbiota in colorectal cancer.
“There is growing evidence that certain bacteria and alterations in the microbiome play a significant role in cancer development, progression, and response to treatment,” said lead study author Garazi Serna, PhD, a postdoctoral investigator in VHIO's Molecular Oncology Group. Prior research involving the group has linked Fusobacterium nucleatum to colorectal cancer and associated Fusobacterium nucleatum persistence after preoperative therapy with a higher risk of recurrence in locally advanced rectal cancer.
This particular study enrolled 740 patients with stage I to III colorectal cancer. Researchers detected Fusobacterium with RNA in situ hybridization in surgical tumor samples. They also explored Fusobacterium nucleatum clearance in stool with quantitative polymerase chain reaction. They then analyzed correlations between intratumoral Fusobacterium in colorectal cancer and patient outcomes.
Key Findings
Twenty-one percent of the participants had detectable intratumoral Fusobacterium, which was more common among right-sided, high-grade tumors with venous, lymphatic, and perineural invasion. Fusobacterium positivity was also associated with reduced immune infiltration.
Patients were followed for a median of 48.6 months. In fully adjusted multivariate models, Fusobacterium positivity was independently associated with a shorter relapse-free survival (hazard ratio [HR] = 1.87; 95% confidence interval [CI] = 1.23–2.84; P = .003) and disease-free survival (HR = 1.84; 95% CI = 1.27–2.70; P = .001); however, it was not associated with a shorter colorectal cancer–specific survival (HR = 1.39; 95% CI = 0.72–2.70; P = .321) or overall survival (HR = 1.51; 95% CI = 0.91–2.50; P = .113).
Adjuvant chemotherapy led to a significant improvement in disease-free survival in patients with Fusobacterium-negative colorectal cancer (HR = 0.38; 95% CI = 0.20–0.74; P = .004), but not in Fusobacterium-positive patients (HR = 0.68; 95% CI = 0.25–1.8; P = .44).
Fusobacterium nucoleatum in the stool following surgery was detectable up to 3 years before recurrence and was linked to an increased risk of relapse (odds ratio = 61; 95% CI = 2.3–1652; P = .01).
The study authors noted that these findings must be prospectively validated in larger cohorts before they can be applied in clinical practice.
DISCLOSURES: The FUSOMAP project is supported by the Fondo de Investigaciones Sanitarias (FIS), Fundación Mutua Madrileña, the Carlos III Health Institute (ISCIII), and Cancer Research UK (CRUK). For full disclosures of the study authors, visit sciencedirect.com.
