Definition of stage II colon cancer
Invasion of the whole intestinal wall without lymph node metastasis (i.e. N0 stage).
Stage II colon cancer is classified as:
IIA T3 tumor penetrates the outer muscular layer to the peri-colorectal tissue
IIB T4a tumor directly infiltrates through the dirty peritoneum
IIC T4b tumor directly invades or adheres to surrounding tissues or organs
Risk of Recurrence and Outcome of Stage II Colon Cancer
Data from a total of 109,953 patients with invasive colon cancer from 1992-2004 from the US Epidemiologic Follow-up and End Results (SEER) database showed that
T3 5-year survival rate 87.5%
T4a 5-year survival rate 79.6%
T4b 5-year survival rate 58.4%
Microsatellite instability (MSI) is also a marker of good prognosis in stage II colon cancer and a predictor of outcome (and possibly harm) in patients who do not benefit from fluorouracil monotherapy, with a recurrence rate of 11% versus 26% for dMMR (MSI-H) versus pMMR (MSI-L, MSS), respectively.
Studies have shown that elevated preoperative serum CEA is also a high factor for recurrence, but no clinical guidelines have included CEA as a reference for whether to treat with chemotherapy.
Clinical studies have shown that adjuvant 5FU monotherapy resulted in an absolute reduction in the risk of death in stage II colon cancer by 3%.5 The SEER database of stage II colon cancer outcomes, grouped by whether or not they received adjuvant chemotherapy, found no significant difference in 5-year OS between the two groups (78% versus 75%) and an HR for survival of 0.91 (95% CI, 0.77-1.09). Of note, a recent analysis derived from the SEER Medicare database containing >24,000 stage II colon cancers showed that stage II patients, even those with more than 1 poor prognostic factor in stage II, did not benefit from adjuvant chemotherapy, with no improvement in 5-year survival (HR,1.03; 95% CI, 0.94-1.13).
The US NCCN 2015 colorectal cancer guidelines recommend that
Low-risk stage II patients may be enrolled in clinical trials, either for observation or to consider capecitabine or 5-FU/LV monotherapy. FOLFOX is not recommended for the treatment of stage II patients without high-risk factors.
Adjuvant chemotherapy, including 5-FU/LV, capecitabine, FOLFOX, CapeOX, or FLOX, should be considered for high-risk stage II patients with T4, poor differentiation (except MSI-H), lymphovascular invasion, perineural invasion, bowel obstruction, perforation or perforation in close proximity to the tumor, uncertain or positive margins, or fewer than 12 lymph nodes. May also be considered.
The European ESMO 2013-2014 Colorectal Cancer Guidelines Clinical Practice Guidelines recommend that
Stage II patients should be considered high-risk if they have at least one of the following clinical features.
A lymph node sampling count <12< span="">.
Poorly differentiated tumor.
Vascular or lymphatic or peripheral nerve invasion.
Tumor exhibiting obstruction or perforation and being pT4.
The Chinese Colorectal Cancer Diagnostic and Treatment Code (2015 version) recommends that
Adjuvant chemotherapy for stage II colorectal cancer. Patients with stage II colorectal cancer should be confirmed to have the following high-risk factors: poor histological differentiation (grade III or IV), T4, vascular lymphovascular infiltration, preoperative bowel obstruction or bowel perforation, and insufficient lymph nodes (<12) detected in the specimen.
Stage II colorectal cancer without high-risk factors is recommended for follow-up observation or chemotherapy with single-agent fluorouracil-based drugs.
For stage II colorectal cancer with high-risk factors, adjuvant chemotherapy is recommended.
Summary
The group of patients with stage II colorectal cancer is a heterogeneous group with different risks of recurrence and large differences in prognosis, with a wide span of 5-year OS (60%-80%). Adjuvant chemotherapy is recommended for high-risk groups, but the evidence is insufficient and individualized assessment and management is needed.