Newer Colorectal Cancer Screening Tests to Replace Guaiac Test
In the U.S., adults aged 50 and older are recommended to participate in colorectal cancer screening. The gold standard of colorectal cancer screening is colonoscopy. However, for many people, colonoscopy is too invasive and uncomfortable. They prefer non-invasive screening methods such as stool tests or virtual colonoscopy.
A stool test is used to detect traces of cancer in the stool. The traces could either be blood as in the case of guaiac test or tumor DNA as in the case of stool DNA.The standard stool test in the last decade or so is the fecal occult blood test (FOBT), also known as guaiac test (GT), which detects the peroxidase activity of heme. This test has low sensitivity for both cancer and adenoma (precursor to cancer). Furthermore, heme can be found in red meat and certain fruits and vegetables, which lead to high rate of false positives.
The most popular guaiac test is Hemoccult-II. According to Zauber et al. (2007), the sensitivity of Hemoccult II is 12.0% , 5.0% and 2.0% for adenomas larger than 10 mm, from 6 to 10 mm, and smaller than 5 mm, respectively.
Collins et al. (2000) compares the accuracy of single stool sample obtained by digital rectal examination with recommended sampling practice based on take-home samples. The digital FOBT is based on a single sample on guaiac-impregnated cards (Hemoccult II). The take-home FOBT is based on 2 samples from 3 consecutive stools on Hemoccult II cards. Patients are given dietary instructions on restricting consumption of red meat, vitamin C, and aspirin before obtaining the samples. The cards were rehydrated before processing. The digital FOBT performed poorly. The sensitivities for large adenomas and cancer are 4.9% and 9.5%, respectively. The rehydrated 6-sample at-home FOBT performed much better, reporting 42.8% sensitivity for cancer and 23.9% for adenomas. The specificity for at-home FOBT reported by Collins is particularly low only 93.9% , in comparison to 97.5% for the digital FOBT.
Currently, there are three alternative stool tests that perform much better than the conventional guaiac test:
- Hemoccult SENSA
- Fecal Immunochemical Test (FIT)
- Fecal DNA
Hemoccult SENSA is a more accurate version of guaiac-based stool test. Hemoccult SENSA is able to detect lower levels of peroxidase activity than conventional GT. In Allison et al (2007), the sensitivity of Hemoccult SENSA for CRC was 64% and for advanced adenomas was 41%, and the specificity was 98%.
Fecal immunochemical test (FIT) uses antibodies specific to human hemoglobin, albumin, or other blood components (e.g., globin). FITs do not depend on peroxidase activity and are highly specific for detecting human blood of colonic origin; eliminating the need for pretest restriction of diet or medication. Allison et al (2007) reported high sensitivities for cancer and adenomas using FIT, 81.8% and 29.5% respectively. The specificity of FIT is reasonably high 97%. Morikawa et al. (2005) reported a 66% sensitivity and 95% specificity for CRC. FIT does not cost too much,3-5 times the cost of the standard guaiac test, but much more accurate and generate fewer false positives.
Fecal DNA detects abnormal DNA in stools, manifested from chromonosomal and microsatellite instabilities. The basis of the Fecal DNA test is Vogelstein ’s observations that the adenoma-carcinoma sequence involves a series of genetic mutations in the APC, K-ras, and p53 genes (Volgelstein, 1988). Furthermore, human DNA from cells shed from the colonic epithelium could be detected in stool. The first commercial Fecal DNA was developed by EXACT science and marketed as PreGen-Plus. It is an assay that test for 23 molecular markers associated with CRC and pre-malignant neoplasms.
The sensitivities for large adenomas and cancer of fecal DNA are 51.6% and 18.6%, respectively. The specificity is 94.4%.
Although FecalDNA has very good performance characteristics, it is too expensive. It costs $300-500 for a test, which is in the same order of magnitude as the cost of colonoscopy. Cost to save one quality-adjust-life-year (QALY) using Fecal DNA can go up to $50-100,000. For FecalDNA to be cost effective, it is recommended that patients are screened every 3-5 year.
Sources:
American Cancer Society. Cancer Facts & Figures 2008. Atlanta, Ga: American Cancer Society; 2008.
Levin B, Lieberman DA, McFarland, et al. Screening and Surveillance for the Early Detection of Colorectal Cancer and Adenomatous Polyps, 2008: A Joint Guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Published online March 5, 2008. CA Cancer J Clin. 2008;58.
