Colorectal cancer
Authors: J. D. Hardcastle
Journal: CA A Cancer Journal for Clinicians (1997)

This issue of CA devoted to three important aspects of colorectal cancer comes at an opportune time, for colorectal cancer is the second most common cause of death from malignant disease in the Western world, and although it is usually preceded by a well recognized premalignant lesion, the diagnosis is often made late in the natural history of the condition, leading to disappointing survival results. There is often a delay between the onset of symptoms and diagnosis. This is principally because of patient delay in reporting symptoms and, to a lesser extent, delay by the primary care physician and hospital specialist, although there is no clear relationship between length of delay and stage of cancer or outcome.1 Nevertheless, there is a need for a greater awareness among primary care physicians of the potential importance of symptoms such as rectal bleeding, change in bowel habit, unexplained and persistent abdominal pain, and anemia so that referral to a specialist physician or surgeon is not delayed. It is disappointing that approximately 20 percent of patients undergoing surgery for colorectal cancer are admitted to hospital as an emergency with obstruction or other life-threatening situations. In many of these cases the cancer has become symptomatic only late in its natural history when the disease is already well advanced. This is disappointing in view of the fact that it is already known that population screening by means of simple fecal occult blood testing can reduce the mortality of colorectal cancer in the group offered screening compared with the control group. Mandel2 and his colleagues demonstrated that screening a group of volunteers older than 50 years every year using the rehydrated Hemoccult test reduced the mortality of colorectal cancer by over 30 percent. Unfortunately, the use of such a sensitive test resulted in more than 10 percent of the acceptors testing positive and requiring investigation by colonoscopy. Indeed, 38 percent of the screened group underwent colonoscopy during the course of the study. A less intensive screening program using unhydrated Hemoccult every two years, which resulted in only four percent of the test group requiring colonoscopy, still reduced mortality 15 to 18 percent.3, 4 These data, taken together with case control studies of both fecal occult blood and rigid sigmoidoscopic screening for rectal cancer, now provide strong evidence that mortality from colorectal cancer can be significantly reduced by population screening. Screening is particularly applicable to individuals belonging to high-risk groups. It is known that approximately 10 to 15 percent of colorectal cancers occur in persons who have a first-degree relative who has had the disease. These persons are approximately twice as likely to develop colorectal cancer compared with the general population, and the risk is greater if their relative was diagnosed with cancer before the age of 45.5 In these individuals endoscopic screening by means of colonoscopy is to be recommended. Approximately five percent of colorectal cancer cases are related to inheritance of autosomal dominant conditions such as familial adenomatous polyposis (FAP) and hereditary nonpolyposis colorectal cancer (HNPCC) syndromes. The phenotype of the FAP syndrome is readily recognizable during teenage years by the development of many hundreds of adenomatous polyps in the bowel. However, HNPCC does not have easily recognized phenotypic characteristics, and in the past the prevalence of the syndrome as defined by the Amsterdam criteria may have been underestimated. Genetic testing suggests that it accounts for about two percent of all bowel cancer. Individuals known to carry HNPCC mutation should be screened by colonoscopy, and as it is likely that the cancers in this condition develop more rapidly through an adenoma stage, colonoscopy should be carried out every two years. As approximately 10 percent of the general population older than 50 years have a close relative with bowel cancer, it is important that both the general public and primary care physicians are educated to provide help to define high-risk families. There is considerable evidence that removal of colorectal adenomas will decrease the risk of developing cancer. The National Polyp Study has shown a significant difference between the incidence of cancer in the screened population after adenoma removal with a cohort of patients previously identified at the Mayo Clinic before the era of endoscopic polypectomy. However, these data must be interpreted with care, as comparable groups can only be achieved by prospective randomization. This has been done in the Minnesota study of fecal occult blood screening, during which 38 percent of the screened group each year underwent colonoscopy with removal of adenomatous polyps. After a 14-year follow-up, no significant reduction in the incidence of cancer in the group offered screening has been demonstrated. These data may simply indicate the length of time necessary for the progression of adenomas to cancer, which may take a number of years. The increasing use of screening sigmoidoscopy results in a number of important issues in the management of patients found to have adenomatous polyps in the left side of the colon. The evidence relating to the need for full colonoscopy in these individuals is fully reviewed. It is important to draw the distinction between an adenoma with high-grade dysplasia and an adenoma containing a focus of invasive cancer. Pathologists should be careful to distinguish between the two and should avoid using the term carcinoma in situ, as this may mislead surgeons into undertaking more radical therapy than is necessary. The chemoprevention of adenomatous change by nonsteroidal antiinflammatory drugs is reviewed only in the context of FAP, but there is now increasing evidence to suggest that these agents may play a part in the prevention of spontaneous adenoma development, which raises the possibility of reducing the risk of cancer in larger populations. The quality of surgery undertaken is crucial to survival of patients with colorectal cancer. It is important that the surgery be undertaken only by surgeons who can demonstrate their skill in removing the tumor intact, with sufficient adjoining tissue to minimize the risk of leaving cancer cells at the site of the excision. There is no doubt that the outcome of colorectal cancer surgery varies considerably among surgeons.6 However, it is important to be careful in evaluating the evidence for this, as case mix factors and chance may play a large part in the observed heterogenicity. The pathologist plays a vital part in providing data to allow the surgeon to assess the adequacy of this work. Several studies have demonstrated that there may be tumor involvement at the circumferential margin of surgical specimens in which the surgeon had considered the margin to be clear.7 This is a particular problem in tumors of the lower or middle third of the rectum, where total mesorectal excision that involves careful dissection of tissues surrounding the rectum and preservation of the pelvic nerves may be helpful. Excellent results have been reported using this technique, and the adoption of the technique in Sweden appears to have been associated with a reduction in the local recurrence rate and improvement in survival.8 There is good evidence that both preoperative and postoperative radiotherapy can reduce local recurrence after surgery for rectal cancer. If the tumor is thought to be advanced, particularly in the anterior rectum, preoperative radiotherapy is indicated, postoperative radiotherapy being considered for those patients with high risk of recurrence because of tumor involvement in margins of tissue removed during surgery.