Future study of colorectal cancer will refine our understanding of the genetics of the disease. This in turn will lead to earlier identification and treatment of high-risk persons. The future may possibly bring the use of genetic interventions to interrupt the adenoma-carcinoma sequence.
Increased awareness of colorectal cancer by the public and by private insurers, government agencies, and medical personnel will result in better use of available screening techniques. Development of preventive drug strategies against colorectal cancer, particularly with drugs that reduce polyp formation or prevent polyp progression to cancer, promises to be a fruitful field of endeavor.
There is ample reason to expect refinement of diagnostic and staging tests for the disease, perfection of surgical and nonsurgical techniques for treatment of large bowel cancer and its complications, and improving chemotherapeutic treatment by means of more effective and less toxic drugs.
A number of molecular markers for colorectal cancer can be measured but it is not yet clear that they have prognostic value or therapeutic implications. Measures of DNA synthesis or cell division are of uncertain value as clinical decision-making tools. Measurement of thymidilate synthase activity in colorectal cancer tissue is one of several markers under investigation as a prognostic indicator.
This could be useful in making decisions regarding the use of adjuvant chemotherapy for certain patients, especially those with stage II or B tumors. Another goal would be to collect a set of markers for cancer risk for an individual who has adenomatous polyps. Presumably, such testing could reflect exposure to colon carcinogens and help define the outlook for an individual. This in turn could narrow the prospective use of screening and diagnostic procedures such as colonoscopy.
Techniques to identify micrometastases in lymph node tissue are in development. These include special stains for cytokeratin, which can identify small clusters or single malignant cells in lymph node tissue. Another method uses a technique known as PCR for detection of CEA in resected lymph nodes. PCR is a technique which permits rapid reproduction of large quantities of short segments of DNA or RNA.
Other techniques include the identification in lymph node tissue of oncogene, or tumor suppressor gene mutations, which occur in the primary tumor. Such techniques may be of use in reclassifying patients whose lesions are stages as II or B by conventional means and in selecting them for potentially life-saving adjuvant chemotherapy. Large clinical trials will be needed to determine if identification of micrometastases by these methods indeed leads to more appropriate treatment and improved progress.
Expression of the enzyme COX-2 by colorectal cancers is highly variable. Greater expressions of COX-2 by tumors are associated with lymph node metastasis, advanced stage of cancer, and poorer long-term outlook for patients. Thus, there could be potential future application of this test as a means of staging and prognostication.
