Prognostic and Molecular Factors in Stage II Colorectal Cancer

Abstract

Over the last 20 years, adjuvant chemotherapy has been administered after surgical resection of tumors for colorectal cancer (CRC) patients with stage III disease to reduce the risk of recurrence of cancer. However, it is controversial as to whether all stage II CRC patients, or at least stage II CRC patients with additional risk factors, should receive adjuvant chemotherapy. Adjuvant chemotherapy in stage II CRC patients may be considered for patients in high-risk groups. It is a high priority to define prognostic factors for these stage II CRC patients to identify high-risk patients at risk of tumor metastases or recurrence and referral of stage II CRC patients for individual assessment. Recent guidelines advocate the consideration of clinicopathological factors such as free bowel perforation or obstruction, lymphatic and vascular invasion, poorly differentiated tumors, fewer than 12 lymph nodes examined, tumors with adjacent organ involvement, and indeterminate or positive margins as strong predictors of a poor prognosis in stage II CRC. Furthermore, with recent advances in basic research attempting to elucidate the underlying molecular mechanisms of carcinogenesis, a variety of candidate genes with potential value for the early detection of cancer have been discovered. Molecular factors such as microsatellite stability and loss of heterozygosity of 18q have been used to identify groups of patients with stage II CRC who have much worse prognoses and may benefit from administration of chemotherapy. Accumulated reports have described the detection of circulating tumor cell-related molecular markers in the peripheral blood of CRC patients, which has important prognostic and therapeutic implications. Consequently, therapeutic decision-making models are likely to be further refined by the inclusion of such molecular markers.