Early Detection of Colorectal Cancer

Detector C is a blood-based screening test for the early detection of colorectal cancer. The test uses Affymetrix technology to evaluate the expression of 202 genes that are altered in response to tumor formation and growth. The test showed a consistently high sensitivity of 90 percent for all four cancer stages (including early stages), and a specificity of 88 percent.

Addressing an Unmet Need in Colorectal Cancer Screening

Most colorectal cancer screening recommendations call for screening beginning at age 50. The most common screening test, the Fecal Occult Blood Test (FOBT), is noted for poor sensitivity and high specificity. Recommendations in some countries also include periodic endoscopic procedures, flexible sigmoidoscopy or colonoscopy. While these procedures are sensitive and specific for identifying precancerous or cancerous lesions, they are invasive and costly. As a result, a 2008 report from the American Cancer Society showed that less than 50% of the targeted U.S. population has adhered to screening recommendations. A similar report on CRC screening in Europe noted that national practices were not standardized. Even the most proactive European programs do not exceed much over 50% participation, and serial participation is worse.

The EU-5 and US screening population (aged 50 to 79) totals 170 million individuals. Approximately 5.1 million individuals (3 percent) have an undetected colorectal cancer (CRC). Only 396,000 CRC cases (7.8 percent) are presently diagnosed annually (EU-5: 220,000, USA: 176,000). Classical screening methods, including haemocult II (gFOBT) and colonoscopy, detect only 5 percent of these 396,000 CRC patients. In 4.7 million individuals affected with CRC, the cancer remains undetected until severe symptoms occur.

In Germany, about 73,000 patients are diagnosed with CRC every year. Due to the risks and inconvenience associated with CRC colonoscopy screening (bowel cleaning, at least one day off work, fear of bleeding events or colon perforations), patient participation is low (3-5 percent per year). Therefore, CRC screening using colonoscopy results in the diagnosis of only 5.400 patients each year. Furthermore, CRC screening, using gFOBT, is declining due to the test's inaccuracy and the difficulties associated with collecting stool samples. There is a great need for a in-vitro diagnostic (IVD) that can detect early stage CRC and serve as a reliable screening tool.

Detector C Overview

During the last years many genomic tests for cancer screening and early detection have been developed. Unlike previous generation genomic tests, Signature Diagnostics AG has developed a new blood-based screening test for the early detection of colorectal cancer. Detector C is convenient, easy-to-use and provides highly accurate results within a short time.

Positive results from a prospective, multi-center clinical study validating Detector C demonstrate its potential to prevent late stage cancers through early detection, which is more effective and ethical than palliative treatment of patients with metastatic disease.

Especially in times where new cancer drugs are rare events, innovations in cancer screening significantly contribute to an improved overall management and overall survival of colorectal cancer patients. Signature Diagnostics AG has developed the best blood-based screening test which will be commercially available in late Q4/2010 to early Q1/2011

Detector C has been successfully validated using an independent set of 343 blood samples including 210 samples originating from patients with all four stages of colorectal cancer and 133 samples from controls over age 55 undergoing colonoscopy for screening purposes. The prospective validation study demonstrated a sensitivity of 0.90 (95% CI: 0.851-0.937) and a specificity of 0.88 (95% CI: 0.812-0.930). The sensitivity results by UICC stage are as follows: stage I: 0.89 (95% CI: 0.774-0.958), stage II: 0.90 (95% CI: 0.788-0.961), stage III: 0.90 (95% CI: 0.805-0.959) and stage IV: 0.93 (95% CI: 0.765-0.991). Detector-C also identified high-grade intraepithelial neoplasia with a sensitivity of 0.66.

Multivariate analysis showed no significant effect in relation to stage, age, gender, tumor localization, or RNA quality on correct prediction. Detector C showed an extremely low false negative rate of only one in 872 tested individuals, which is four times lower than the false negative rates of other blood-based tests. In comparison to Haemocult II (gFGOBT), Detector C has a seven times lower rate of false negatives.

Detector C offers a Breakthrough in Colorectal Cancer Screening for Patients and Caregivers

To our knowledge, Detector C is the safest and most accurate blood-based screening test available, making it particularly well suited for population-wide CRC-screening. Detector C is appropriate for all individuals who want to get tested for colorectal cancer and who did not undergo colonoscopy during the last 5 years. The unprecedented low number of false negatives warrants its use prior to colonoscopy and as an alternative to stool-based tests. Detector C has the potential to provide an early warning to hundreds of thousands of individuals with early stage colorectal cancer, enabling them to begin treatment while their disease is still curable. Patients tested positive with Detector C should in any case undergo colonoscopy for confirmation.