Colorectal cancer (CRC) is the second leading cause of cancer-related death for men and women in the United States. Unfortunately, despite well defined recommendations, compliance with screening protocols remains suboptimal.

 

However, for those patients diagnosed with CRC, there are several new and novel molecular and cellular diagnostic assays to assist the clinician with patient management decisions, including treatment selection and clinical course monitoring. It is anticipated that, as the demand for personalized medicine grows so, too, will the availability of these innovative laboratory tests.

 

For patients with metastatic carcinoma of the colon or rectum (primary or recurring) or EGFR positive metastatic disease, The Invader^® UGT1A1 Molecular Assay (Hologic^®) can be performed to identify patients who may be at risk for therapy-related toxicity if treated with irinotecan (Camptosar™). The assay detects molecular (DNA) variations in the UGT1A1 gene that influences a patient’s ability to effectively metabolize the drug.

 

In other instances, certain treatment options may not be ideal for patients found to have tumors carrying mutations in either the KRAS or BRAF genes, as the presence of these mutations can adversely affect clinical responses to anti-epidermal growth factor receptor (anti-EGFR) therapies such as cetuximab (Erbitux^®) and panitumumab (Vectibix^®). As the incidence of KRAS gene mutations in CRC patients is approximately 35-45 percent (10-15 percent for BRAF mutations), identifying patients who will benefit from treatment is vital to determining appropriate treatment strategies and ensuring the best clinical outcomes. Based on the annual incidence of new metastatic CRC cases each year, a savings of more than $604 million for cetuximab alone could result through treatment stratification based on KRAS mutation status.¹

 

In January 2009, the American Society of Clinical Oncology released its first Provisional Clinical Opinion recommending that all patients with CRC have tumors tested for KRAS gene mutations (codon 12 and 13) prior to the initiation of therapy and the National Comprehensive Cancer Network updated its 2010 practice guidelines to recommend the option that patients with metastatic colorectal cancer have BRAF mutation testing (V600E) performed as part of their evaluation when the KRAS gene is not mutated.

 

To monitor treatment effectiveness for individual patients on chemotherapy, the CellSearch™ Circulating Tumor Cell Test (Veridex, LLC) is also available. CellSearch identifies and counts circulating tumor cells (CTCs) in a blood sample. In metastatic colorectal cancer, a CTC count of three or more per 7.5 mL of blood at any time during clinical course monitoring is associated with a poor prognosis and is predictive of shorter progression-free survival and overall survival.

 

It is recommended that physicians order a CellSearch test before initiating a new therapy, again at the patient’s first follow-up visit, and thereafter at monthly intervals and in conjunction with CT scans. If CTC levels are elevated from baseline to routine follow-up visits, a physician may choose to evaluate the appropriateness of alternative treatments. Additionally, serial testing with CellSearch and the carcinoembryonic antigen (CEA) test allows physicians to monitor patient status at any time during therapy.

 

Health management of patients with colorectal cancer may require an integrated approach to minimize treatment cost and maximize treatment efficacy.

 

 

 

1. V. Shankaran et al. (2009). Economic implications of KRAS testing in metastatic colorectal cancer (mCRC). Gastrointestinal Cancers Symposium. Abstract No. 298.

 

2. Lievre A et al. (2007). KRAS Mutation Status Is Predictive of Response to Cetuximab Therapy in Colorectal Cancer. Cancer Res 66:3992-3995.

 

3. Tol J et al (2009). BRAF mutation in metastatic colorectal cancer. NEJM 361: 98-99.

 

4. Di Nicolantonio F et al (2008). Wild-type BRAF is required for response to panitumumab or cetuximab in metastatic colorectal cancer. J Clin Oncol 26:5705-5712.

 

5. Cohen S.J et al. (2008). Relationship of Circulating Tumor Cells to Tumor Response, Progression-Free Survival, and Overall Survival in Patients with Metastatic Colorectal Cancer. J Clin Oncol 26 (19):3213-322

 

6. National Cancer Institute: www.cancer.org, www.cancer.gov/cancertopics/1. types/colon-and-rectal.

 

7. Third Wave Technologies: www.twt.com, www.twt.com/company/2. pressreleases/2005/aug_22a_2005.html.