Is There a Role for Routine p53 Testing in Colorectal Cancer?

Abstract

The availability of new and more effective chemotherapeutic and molecular targeted agents has resulted in improved treatment of regional and advanced colorectal cancer. However, thefinancial cost and the morbidity associated with the new treatments have increased as well, and to date no reliable marker capable of selecting patients who will benefit from a specific treatment has been identified. Individualizingtreatmentbasedonthemolecularprofileof the patient and the tumor could lead to considerable improvement in treatment cost and outcomes. Although all patients with colorectal cancer would benefit from better prognostic and predictive markers, risk-benefit is particularly important for candidates for adjuvant therapy, which may expose patients already cured by surgery to unnecessary risk or to a treatment that fails to maximize their chances of cure from micrometastasis. The use of adjuvant oxaliplatin regimens after resection of stage II or III colon cancer is a good example of this clinicalconundrum.Theadditionofoxaliplatintofluorouracil and leucovorin improves the 3-year disease-free survival rate, and has been approved for high-risk resected coloncancerbytheUSFoodandDrugAdministration,but it is clear that not all patients benefit equally from oxaliplatin. In fact, when patients already cured by surgery alone and patients who experience disease recurrence despite treatment are excluded, fewer than 30% of stage II and III patients actually benefit from the use of any adjuvant chemotherapy.Unfortunately,wecurrentlyhavenopracticalwayofidentifyingthosewhowillandthosewhowillnot benefit from the treatment. We still identify which patients should receive adjuvant chemotherapy by their pathologic staging, a tool that has changed little since originally proposed by Dukes more than 70 years ago. 1 The choice of the chemotherapy regimen to be used also lacks sophistication and the currently accepted regimens are applied to the entire patient population without consideration for individual tumor sensitivity or for the patient’s tolerance for