Intratumoral Fusobacterium Identified as Prognostic and Predictive Biomarker in Resectable Colorectal Cancer
核心洞察
The multicenter FUSOMAP study found that intratumoral Fusobacterium was present in 21% of resectable stage I–III colorectal cancer (搜索) tumors and was associated with more aggressive disease and reduced immune infiltration.
Fusobacterium positivity independently predicted shorter relapse-free survival (HR = 1.87; P = .003) and disease-free survival (HR = 1.84; P = .001), but not overall or cancer-specific survival.
Adjuvant chemotherapy (搜索) significantly improved disease-free survival in Fusobacterium-negative patients (HR = 0.38; P = .004) but showed no significant benefit in Fusobacterium-positive patients (HR = 0.68; P = .44).
The presence of intratumoral Fusobacterium in surgical tumor samples identifies a clinically more aggressive subtype of colorectal cancer (搜索) (CRC) that derives limited benefit from adjuvant chemotherapy (搜索) and carries a higher risk of disease recurrence, according to first results from the multicenter FUSOMAP project published in ESMO Open. The findings position Fusobacterium as a potential prognostic and predictive biomarker that could help personalize treatment strategies for patients with resectable stage I–III CRC.
"These results suggest that Fusobacterium could be a powerful tool and biomarker for personalizing colorectal cancer (搜索) 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 (搜索)'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."
The FUSOMAP Study: Largest European Microbiota Investigation in CRC
FUSOMAP is a three-year multicenter project supported by the Fundación Mutua Madrileña, the Carlos III Health Institute (ISCIII), and Cancer Research UK (CRUK). The observational study brings together nine Spanish hospitals across seven autonomous communities to develop microbiota-based diagnostic and prognostic models by mapping intratumoral Fusobacterium and associated gut microbiota in resectable stage I–III CRC. It is considered the largest European study of microbiota in colorectal cancer (搜索).
CRC remains one of the leading causes of cancer-related morbidity and mortality worldwide. Despite curative-intent surgery and adjuvant chemotherapy (搜索), disease recurrence occurs in more than 30% of patients with stage II–III CRC. Current risk stratification relies on clinical factors and anatomopathological features such as tumor stage, grade, and the presence of venous, lymphatic, or perineural invasion. However, as Nuciforo noted, "these factors have limited value in identifying patients that could benefit from adjuvant chemotherapy, and many patients may be over- or undertreated as a result."
Key Findings: Fusobacterium Positivity and Clinical Outcomes
The study enrolled 740 patients with stage I to III colorectal cancer (搜索). Researchers detected Fusobacterium using RNA in situ hybridization in surgical tumor samples and explored Fusobacterium nucleatum (搜索) clearance in stool with quantitative polymerase chain reaction. They then analyzed correlations between intratumoral Fusobacterium and patient outcomes.
Twenty-one percent of 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.
At a median follow-up of 48.6 months, Fusobacterium positivity was independently associated with 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) in fully adjusted multivariate models. However, it was not associated with shorter colorectal cancer (搜索)–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).
Differential Benefit from Adjuvant Chemotherapy (搜索)
A critical finding of the study was the differential response to adjuvant chemotherapy (搜索) based on Fusobacterium status. Adjuvant chemotherapy led to a significant improvement in disease-free survival in patients with Fusobacterium-negative colorectal cancer (搜索) (HR = 0.38; 95% CI = 0.20–0.74; P = .004). In contrast, Fusobacterium-positive patients derived no statistically significant benefit (HR = 0.68; 95% CI = 0.25–1.8; P = .44).
"Adjuvant chemotherapy (搜索) significantly improved disease-free survival in Fusobacterium-negative patients, but not in those with Fusobacterium-positive tumors," said Elena Élez, Medical Oncologist at the Vall d'Hebron University Hospital, Head of VHIO's Gastrointestinal Tract Tumors Group, and co-author of the study.
Stool-Based Detection and Early Relapse Prediction
The study also provides the first evidence that persistence of Fusobacterium in the intestinal microbiota following surgery is associated with an increased risk of CRC recurrence. Through longitudinal analysis of stool samples collected at follow-up, investigators observed that Fusobacterium nucleatum (搜索) could be detected up to three years before relapse, with detection linked to a markedly increased risk of recurrence (odds ratio = 61; 95% CI = 2.3–1652; P = .01).
"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 had linked Fusobacterium nucleatum (搜索) to colorectal cancer (搜索) and associated its persistence after preoperative therapy with a higher risk of recurrence in locally advanced rectal cancer.
Toward Clinical Implementation
The study authors emphasized that these findings must be prospectively validated in larger cohorts before they can be applied in clinical practice. If confirmed, Fusobacterium detection could enable clinicians to identify patients with a poorer prognosis who might derive less benefit from chemotherapy, anticipate possible relapse, and implement more appropriate surveillance strategies tailored to individual risk profiles.