Screening of average-risk individuals for colorectal cancer S.J. Winawer,' J. St. John,2 J. Bond,3 J.D. Hardcastle,4 0. Kronborg,5 B. Flehinger,6 D. Schottenfeld, N.N. Blinov,8 & the WHO Collaborating Centre for the Prevention of Colorectal Cancer9 Recent developments in screening, diagnosis and treatment of colon cancer could lead to a reduction in mortality from this disease. Removal of adenomas, identification of risk factors, appropriate application of accurate diagnostic tests, and aggressive anatomic-surgical resection of colon cancers may already be having a favourable impact. Screening ofaverage-risk populations over the age of 50 also offers promise in the control of this important cancer. The disease is of sufficient magnitude to deserve detection at an early stage with better prospects of patient survival, since screening tests with moderate sensitivity and high specificity are available. Flexible sigmoidoscopy and faecal occult blood tests are sufficiently acceptable to be included in case-finding among patients who are in the health care system. The results of current controlled trials involving more than 300 000 individuals for evaluating the impact of screening on mortality from colon cancer are needed before this approach can be recommended for general public health screening of the population. Further research is required to develop better screening tests, improve patient and physician compliance, and answer more definitively critical questions on cost-effectiveness. Mathematical modelling using current and new data can be used to determine the effectiveness of screening in conjunction with recommendations for primary prevention. Introduction relating to feasibility include the rate of positive tests, Colorectal cancer has an annual incidence worldwide sensitivity, specificity and predictiveness of the tests, ofmore than halfa million cases and ranks as the third and patient compliance. Effectiveness depends on most common cancer, preceded by only lung and cancer staging, survival, mortality, and cost-effective- stomach cancers. Countries with a high incidence of ness. Detection ofearlier-stage cancers, often associated colorectal cancer include Australia, Canada, France, with improved survival, is critical although bias could Italy, New Zealand, the Scandinavian countries, United influence the results. For example, cancers may be Kingdom and the USA (1). detected earlier but without any real increase in The potential benefit of screening for colorectal survival (lead-time bias), or only the more favourable cancer is based on: (1) the well-established relationship cancers may be detected by screening because they between survival and stage of disease, and (2) the are slow-growing cancers (length bias) (2,3). Over- observation that diagnosis and removal of premalig- diagnosis is yet another bias resulting in treatment of nant adenomas could lead to a decrease in the future cancers that would not have been identified. The incidence of colorectal cancer (2-7). validity of screening can be assessed and bias reduced Several factors influencing the feasibility and if the mortality from colon cancer can be examined; to be examined. Those this is difficult and depends on ascertaining the effectiveness of screening need follow-up of all individuals in a cohort and establish- ing systematic mortality reviews (2,3). I Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. Requests for reprints should be sent to this author. Risk factors and screening 2 Royal Melbourne Hospital, Victoria, Australia. 3Veteran's Administration Medical Center, Minneapolis, MN, USA. Risk factors 4University Hospital, Department of Surgery, Nottingham, England. Odense University Hospital, Odense, Denmark. Age. Risk for colorectal cancer increases slightly at age IBM Research Center, Yorktown Heights, New York, USA. 40 and more sharply at 50 years, doubling thereafter Department of Epidemiology, Schdfol of Public Health, University with each decade (3). Individuals who are at risk by of Michigan, Ann Arbor, Ml, USA. ' Petrov Research Institute of Oncology, Leningrad, USSR. virtue of age only and who have no other associated ' Memorial Sloan-Kettering Cancer Center, Gastroenterology Ser- high-risk factors are considered at "average or stan- vice, New York, NY, USA. dard risk" for the disease. Several high-risk groups can Reprint No. 5102 be identified (Table 1). Bulletin of the World Health Organization, 68 (4): 505-513 (1990) t World Health Organization 1990 5S0 S.J. Winawer et al. Table 1: Risk for colorectal cancer only a small number of new cases each year. Duration ofthe disease and its anatomical extent are two factors Average risk: in the cancer risk, which begins to rise after seven years Men and women aged 50 years and older of disease in patients with involvement of the entire High risk: colon and after 15 years when there has been only 1. Inflammatory bowel disease left-sided colitis. Proctitis alone appears to carry no 2. Familial adenomatous polyposis syndromes, including increased risk (14). This matter will be discussed in Gardner and Turcot syndromes another article. 3. Juvenile polyposis 4. Hereditary non-polyposis colorectal cancer syndromes 5. Family history of colorectal cancer or adenomas 6. Past history of colorectal cancer or adenomas Screening tests 7. Past history of breast, endometrial or ovarian cancer Screening using rapid, simple tests should separate well persons who have a high probability of a disease from those with a low probability (2,3). The screening Colorectal neoplasul. Patients who have had one colo- test is not intended to be diagnostic, and persons with rectal cancer have a 5-10% risk for a subsequent positive findings should be referred for diagnosis and colorectal cancer (3). Patients with one colorectal treatment. Three tests that currently fulfil these criteria cancer have a 1.5-5% risk that an additional colo- are the stool blood test, digital rectal examination, and rectal cancer is present at the same time. The preva- sigmoidoscopy. The last two can be considered clinic- lence of adenomas in Western countries is as high as ally diagnostic in symptomatic people. 40-50% in older age groups (8), and there is con- The identification of cancer by digital rectal siderable evidence that most colorectal cancers arise examination is now less frequent as a result of the from an adenoma or neoplastic polyp (8). Only proximal shift in the site of colorectal cancers. Recent a proportion of colonic polyps that are detected are statistics indicate that less than 10% are detectable by true adenomas. In the U.S. National Polyp Study, digital examination (2,3). There are several sigmoido- adenomas accounted for 68% of the polyps removed scopes available now: rigid scopes 25cm in length, by colonoscopy in the initial examination. Individuals 35-cm fibre-optic sigmoidoscopes, 60-cm fibre-optic presenting with one adenoma have a 50% likelihood of sigmoidoscopes, and 40-60-cm video endoscopes additional adenomas and a 30% likelihood of additional (15-18). The average depth of insertion of the rigid adenomas one year after their colons have been cleared sigmoidoscope by skilled examiners is 20cm or less. ofall adenomas (9). The time sequence from a normal- Studies demonstrated that only the distal 16 cm of the appearing colon through the stage of adenoma and rectosigmoid is well examined by the rigid instrument. then to cancer has been studied using mathematical The flexible sigmoidoscope has a 2-3 times greater models and clinical observations. These studies suggest yield for adenomas and cancer as compared to the that the process develops slowly over many years (9). rigid scope and can adequately examine the entire rectosigmoid, where about 50% of the cancers and Genetic predlspositon. Genetic syndromes include adenomas occur (15). The effectiveness of sigmoido- familial adenomatous polyposis; Gardner, Turcot, and scopy in screening has not been well studied, but some Peutz-Jeghers syndromes; juvenile polyposis and data are available. In one study more than 26 000 hereditary non-polyposis colorectal cancer syndrome asymptomatic patients had 58 cancers detected (6). Of (10). These account for approximately 5% of the these, 81% were in stages A and B ofDukes' classifica- colorectal cancer cases each year, and all follow an tion and the 15-year survival was 90%. This was an autosomal dominant mode of inheritance. Until uncontrolled study with follow-up of only the cancer recently, genetic factors were considered to be impor- cases. Studies evaluating the efficacy ofperiodic Multi- tant only in these syndromes, the majority of colorec- phasic Health Checkups in the Northern California tal cancer cases being "sporadic". However, several Kaiser-Permanente programme indicated a reduced studies have reported a threefold excess of cancer and mortality from colorectal cancer. Rigid sigmoidoscopy a high frequency of adenomas among first-degree was part of the multiphasic check-up but was not relatives of patients with colorectal cancer (10). A specifically studied. This mortality reduction was sizeable proportion of "sporadic" adenomas and reconfirmed in a 16-year follow-up but the precise role colorectal cancers may be genetically determined by ofsigmoidoscopy was not clear (19-21). Adenomas are an autosomal dominant mode with low penetrance detected by sigmoidoscopy at a higher frequency than (11). This will be discussed in another paper. carcinomas (15). There are no controlled trials in progress