High-Risk Features of Colon Adenocarcinoma

Established High-Risk Features

T4 tumors, which penetrate visceral peritoneum or invade surrounding organs, are associated with substantially worse survival outcomes and are the strongest independent predictor of lymph node metastasis and recurrence, according to the American Society of Clinical Oncology 1, 2
Poorly differentiated or undifferentiated histology is associated with increased risk of lymph node metastasis and recurrence, with a relative risk of 5.1, as reported by the American Gastroenterological Association 3, 4
Tumor budding, defined as ≥10 buds (grade BD3), is a significant predictor of lymph node metastasis, with the American Joint Committee on Cancer noting a relative risk of 5.1 1, 3
Perineural invasion is an independent risk factor for recurrence, as stated by the National Comprehensive Cancer Network 1, 4
Lymphovascular invasion is associated with a 5.2-fold increased risk of lymph node metastasis, according to the American Society of Clinical Oncology 3, 4

Intestinal obstruction at initial presentation is a high-risk feature, as reported by the American College of Surgeons 1, 4
Tumor perforation at initial presentation is also a high-risk feature, with the American Society of Clinical Oncology noting its significance 1, 4

Inadequate lymph node sampling, defined as <12 lymph nodes examined, is a high-risk feature, as stated by the American Joint Committee on Cancer 1, 2
Positive or close resection margins (<1mm) are particularly important for pedunculated malignant polyps, with the National Comprehensive Cancer Network noting their significance 3, 4

Patients with stage II colon cancer and ≥2 high-risk features have worse 5-year disease-free survival (74.8%) compared to those with one risk factor (87.3%), as reported by the International Duration Evaluation of Adjuvant Chemotherapy collaboration 1

The American Society of Clinical Oncology recommends that adjuvant chemotherapy be offered to patients with T4 tumors (stage IIB/IIC), with discussion of potential benefits and risks 1, 2
Adjuvant chemotherapy may be offered to patients with T3 tumors and high-risk features, especially with multiple risk factors, as stated by the National Comprehensive Cancer Network 1, 5
The American Society of Clinical Oncology notes that adjuvant fluoropyrimidine-only chemotherapy is not routinely recommended for dMMR/MSI-H tumors, regardless of other risk factors 1

Depth of submucosal invasion >1mm is associated with increased risk of lymph node metastasis (RR 5.2) in non-pedunculated malignant polyps, as reported by the American Gastroenterological Association 3
Circulating tumor DNA (ctDNA) is emerging as a potential predictive factor, though insufficient evidence currently exists to include it as a standard high-risk feature, according to the American Society of Clinical Oncology 1

Poorly differentiated histology in MSI-H/dMMR tumors should not trigger adjuvant chemotherapy, as these patients may not benefit from fluoropyrimidine-based therapy, as stated by the National Comprehensive Cancer Network 1, 5
Failing to assess mismatch repair/microsatellite instability status in stage II colon cancer can lead to suboptimal treatment, with the American Society of Clinical Oncology noting its importance 1