Screening of average-risk individuals for 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 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- 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, 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 , 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 (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 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 for evaluating the long-term benefit of the Inflammatory bowel disease. is a risk flexible scopes. factor for colorectal cancer (12-14), but accounts for The testing of stool for occult blood was first

50 WHO Bulletin OMS. Vol. 68. 1990 Screening of average-risk Individuals for colorectal cancer proposed in 1901 (22-24) and the impregnated guaiac performance with proximal colonic lesions and after slide-test was introduced by Greegor as a screen for degradation of globin during storage, and about the colorectal cancer (24). While on a high fibre, meat-free test's specificity before their ultimate place in screening diet, asymptomatic patients were asked to prepare two can be determined. samples of stool daily for three days on guaiac slides. Non-haem peroxidases, vitamin C and iron do The slides were tested with a hydrogen peroxide not interfere with the Hemoquant test, which is not developer and colorectal cancer was detected at a early affected by degradation ofhaemoglobin in the intestine pathological stage in patients who had positive tests or during storage. However, the test is influenced by (44). A positive test is caused by the phenolic oxidation meat in the diet and by ingestion of aspirin and other of the guaiac to a blue compound, catalysed by the drugs that could increase blood loss. Early hopes that peroxidase-like enzymatic activity of haemoglobin. Hemoquant could be used to identify the anatomical Other compounds than haemoglobin with a peroxi- level of bleeding in the have not dase-like activity, mainly in certain uncooked veget- been fulfilled. Concerns include questions about its ables and fruits, can produce a positive test (22,25). ability to distinguish betwen physiological and patho- Although dietary factors have not been fully studied, logical blood loss, interference by diet and drug data indicate that diet has little effect on the standard ingestion, and the relatively high cost of the test. In guaiac slide-tests but has a marked effect on the more addition, its increased sensitivity is at the sacrifice of sensitive guaiac tests, including tests performed after specificity. Maintenance of high specificity with high hydration of the slides (25). Elimination of red meat sensitivity may be possible with the new sensitive and the small number of peroxidase-rich raw veget- guaiac slide-test and with the new immunochemical ables and fruit will improve the test's specificity and tests (30). reduce false positives (25). Iron and laxatives have an Several studies and programmes initiated around unpredictable effect on positives and negatives, while the world to evaluate screening with the stool-blood vitamin C inhibits the test reaction, causing a false tests confirm that this has potential value for colo- negative in the presence of bleeding (22,23). Positive rectal cancer (23,28,29,31-33). A large study is in stool-blood tests can result from physiological blood progress in the Federal Republic of Germany to en- loss and benign bleeding lesions, as well as from courage screening ofasymptomatic women and men in neoplastic bleeding lesions (22,23). Isotope studies doctors' offices on a periodic basis (34). There are five have shown fluctuation of occult bleeding from colo- controlled trials now studying the possible usefulness rectal adenomas and cancer, large adenomas bleeding of the stool-blood test in screening for colorectal more than the smaller ones. Data also suggest that the cancer (Table 2) (28,35-39). A trial was started in 1975 blood loss may have to be greater from the right colon by the Memorial Sloan-Kettering Cancer Centre- and than from the left colon to produce a positive test the Strang Clinic to evaluate the stool occult-blood (22,26,27). Studies have been carried out on possible test for detection of colorectal cancer in conjunction improvements in the guaiac test performance. with rigid sigmoidoscopy in the setting of compre- Hydration ofthe slides produces a higher positiv- hensive preventive medical examinations (35). ity rate and leads to more cancers detected, but also Patients over 40 who presented at the clinic were a larger number of false positive reactions with result- enrolled and allocated to the study and control group ing unnecessary diagnostic evaluations (26,28,29). based on the date of enrolment. All 21 756 par- Other stool-blood tests have been introduced ticipants underwent a comprehensive examination including: immunochemical tests that are specific for which included a general physical examination, a human haemoglobin, a quantitative test for blood health history questionnaire, and 25-cm sigmoido- (Hemoquant@) based on the fluorescence of haem- scopy. Patients assigned to the study group were derived porphyrins, and more sensitive guaiac slide- also offered stool-blood testing, while control tests. Some of these tests have been evaluated and patients were not. Incorporation of the stool-blood compared with the standard guaiac-based slide-test test was feasible with approximately 75% of patients (22,23,30). who were willing to prepare their slides at the time The immunochemical tests, which utilize anti- of their enrolment. The overall rate of positive bodies developed against human haemoglobin and tests was 1.7% with nonhydrated slides and was depend upon the globin being intact, are not affected strongly age-dependent. The rate of positivity was by diet, vitamin C or iron. Because globin is digested in higher for patients who had not had periodic sig- the stomach and , these tests have an moidoscopic examinations in previous years. The extremely low sensitivity for bleeding arising from the overall predictive value of the test for adenomas and upper gastrointestinal tract. Initial experience indi- cancer was 30% and was also greatest on first cates that the tests have a high sensitivity for colonic screening and strongly age-dependent (poor for those bleeding, but more information is needed about their under age 50). The majority of patients with a positive

WHO Bulletin OMS. Vol. 68. 1990 507 S.J. Wlnawer et al.

Table 2: Controlled trials of stool-blood testing In screening for colorectal cancera

Dukes' A & B stage cancers (%)

Cohort Positivity Predictive value (%) Screened Control size rate (%) (adenomas & cancer) group group

Goteborg, Sweden 27 000 1.9 22 65 33 Nottingham, England 150 000 2.1 53 90 40 New York, USA 22 000 1.7 30 65 33 Minnesota, USA 48 000 2.4 31 78 35 Funen, Denmark 62000 1.0 58 81 55

This Table is derived from multiple sources and summarizes mainly the data from non-hydrated slides although hydrated slides have also been used in a phase of some programmes. The data are primarily from initial screening. Dukes' A stage cancers accounted for 34-65% in the screened groups compared with 8-24% in the control groups (see text and references for details). Modified from a previously published Table (3). stool-blood test underwent diagnostic procedures group (52 258 subjects) 53% completed the stool- within a year after their tests. The barium enema blood test resulting in 2.3% positive tests for non- missed 25% of the neoplastic lesions found through hydrated slides with a predictive value for cancer and colonoscopy. The sensitivity for the stool-blood test adenoma of 53% initially and a yield of cancer of 2.3 for cancer was estimated at 70% and specificity at per 1000 persons screened; 53% of cancers detected 98%. A distinct stage difference was observed with were in stage A, compared with 10% in the control respect to those cancers found on the first (prevalence) group. Estimated sensitivity was 72% and specificity screen. The screened group had 65% oftheir cancers in 98%. Rescreening during every other year is planned. Dukes' stage A or B, compared to 33% in the control A fourth controlled trial ofscreening is in progress group. in Sweden and involves 27 700 inhabitants ofGoteborg, A second controlled trial evaluating stool occult- aged 60-64 (28). The rate of positivity in the screened blood testing was initiated in the USA in 1975 at the group was 1.9% using nonhydrated slides and 5.8% University of Minnesota (38). In this study, 48 000 using rehydrated slides. In the initial screen, 65% ofthe participants aged 50 and older were randomly allo- cancers were in Dukes' A or B stage, compared to 33% cated into one of three study groups: those who were in the control group. The estimated sensitivity for offered stool-blood testing each year, those who were cancer was 52%, which is much lower than observed in offered testing every other year, and a control group. the four other trials. A fifth large population-based, Compliance with slide preparation was 75% and the controlled trial has been initiated in Denmark (37). In initial rate of positivity was 2.4% but has increased this study, 62 000 participants aged 50-74 were markedly, primarily because of use of the hydrated- randomly allocated into either a study group (those slide test. Of the 80% of patients with positive tests who were offered stool-blood testing every other year) who underwent diagnostic evaluation, 31 % had either or a control group. The first test was completed in 66% adenomas or cancer ofthe colon or ; 78% ofthe of those in the former group with a slide positivity of cancers were in Dukes' stage A or B, compared to 35% 1.0%, which is the lowest reported on a first screen. in the control group. The single-column barium enema The trials thus far appear to have similar rates of had poor sensitivity and was discontinued and colono- positive slide-tests for nonhydrated slides (1.0% to scopy was considered extremely important. This study 4.0%), similar predictive values for adenoma and is now in a rescreening and follow-up stage. cancer (22% to 53%), and a shift to earlier Dukes' A large, controlled, population-based trial was staging (65% to 90% in Dukes' A and B). All data started more recently in England with asymptomatic indicate an improved sensitivity for cancers but loss of individuals identified from family doctor registries and specificity when the slides are hydrated. The sensitivity allocated randomly to test and control groups (39). of the nonhydrated slide has been estimated to be Recruitment of 156 000 persons aged 50-74 will be 70-80%, with one study reporting 52% sensitivity (28). completed in 1990. Screening of the first 107 349 Complete evaluation of the colon is clearly necessary subjects recruited has been completed. In the test and colonoscopy is now being used to establish the

WHO Bulletin OMS. Vol. 68, 1990 Screening of average-rlsk Individuals for coloresal cancer

diagnosis. As yet, survival data are not available, with medical services, to be better informed about except in one programme (35), but can be expected to serious illness, and to be more optimistic and less be favourable given the improvement in staging. frightened about cancer. An American Cancer Society Mortality data will be forthcoming within the next few survey showed that often there were disturbing public years after complete follow-up so that systematic misconceptions regarding colorectal cancer (47). mortality reviews can be accomplished. It will be Patients have been shown to have a high acceptance of important to see whether the early identification of sigmoidoscopy when they present for a general exam- colonic adenomas and their removal will lead to ination (over 90% in the New York programme). a reduced incidence of colon cancer in these patients. However, patients in general have not demonstrated a willingness to return for repeat rigid sigmoidoscopy. Diagnosis and treatment This attitude may change with greater use of flexible Complete dignostic evaluation ofpatients with a posi- sigmoidoscopes. Although the American Cancer tive screening test is essential for effectiveness of the Society surveys indicate an increasing emphasis on screening programme. Sensitive techniques are now early cancer detection and increased use ofstool-blood available for accurate clinical diagnosis of colonic testing, there is a variable approach by physicians to lesions (40, 41) but there is debate on whether colono- the diagnostic investigation of patients with a positive scopy or barium enema should be the initial test of screening test (48). choice. There are no unbiased controlled studies comparing the independent performance of barium Cost-effectiveness enema with colonoscopy except for the National Polyp Study currently in progress. The double- One cost-benefit analysis suggested a financial savings contrast barium enema is superior to the single column and a projected increase in life expectancy as a result of type in most hands for the diagnosis ofsmall adenomas stool testing (49). Mathematical models have given us and small cancers. The entire colon can be examined some insights into the range of cost-benefit and cost- well including the caecum by experienced endoscopists effectiveness expectations (50). Although these models in more than 90% of patients, usually in 15-20 do not provide definitive answers, they summa- minutes. Colonoscopy has been shown in many studies rize available data and can provide future research to have a higher sensitivity than the barium enema for directions. neoplastic lesions of the colon, especially those under 1 cm in size; in addition, biopsies and cytology can be Treatment of detected cancers performed and polyps can be removed. Colonoscopy, Many reviews of colorectal cancer surgery are avail- however, costs more than the barium enema and has able, with extensive discussion of surgical oncology a greater risk of perforation (42). The decision to use principles and survival statistics (51). Although sur- either or both these diagnostic tests is an individual vival relates clearly to the stage ofcancer at the time of matter based on the above factors as well as available resection, aggressive anatomic surgery has been shown resources. to provide the highest chance ofcure for each stage. In addition, colorectal cancer provides a unique oppor- Attitudes tunity for control of the disease because of an identifi- Patients' acceptance of stool-blood testing has been able premalignant adenomatous stage. In the past, good in controlled trials, but was as low as 15% in removal of adenomas above the reach of the rigid community programmes (43). Sustained interest in sigmoidoscope required and colotomy, rescreening has been difficult for some programmes. In with the attendant morbidity and mortality. These the New York trial, for example, while acceptance was risks have been markedly decreased with the introduc- high for the first screen, the patients were reluctant to tion of colonoscopic polypectomy (51). return personally or send slides in for rescreening despite intensive efforts. In the English trial, special Recommendations measures to encourage compliance were found to be There is a difference between general population very helpful in raising acceptance from 38% to over screening and case-finding in patients who enter 50%. Patients with positive screening tests complied a medical care setting. The perspective may be different with diagnostic studies to a fairly high extent in all of for individuals in the health care system who seek the trials. check-ups to prevent lethal and morbid consequences Factors influencing patients' acceptance of screen- ofadvanced cancer. For physicians who elect to screen ing have been studied (44-46). Acceptors are more asymptomatic people in their practice for occult stool- likely to have had positive attitudes towards prevent- blood, one can provide certain mathematical projec- ive health practices, to have had more recent contacts tions based on available data. Approximately 2% of

WHO Bulletin OMS. Vol. 68. 1990 509 S.J. Winawer et al. patients will have a positive test and at least one out of flammatory bowel disease or a past history of ade- four ofthese people will have an adenoma or cancer on nomas or colorectal cancer; they need individualized further investigation. This neoplastic yield is compar- surveillance according to guidelines for high-risk able to that found in high-risk groups. Unfortunately, people. approximately 30% of the cancers and a majority of 4. Asymptomatic men and women seeking check- adenomas may be missed by one screening with ups who have no risk factors should have a digital standard guaiac slide tests. The anatomic area with the rectal examination annually beginning at age 40, highest rate of misses is the rectosigmoid. a stool occult-blood test annually beginning at age 50, The American Cancer Society, the International and sigmoidoscopy every 3-5 years beginning at age Workgroup on Colorectal Cancer, and the U.S. 50. National Cancer Institute (NCI) have recommended 5. A patient with a positive stool test should have screening guidelines, while other groups such as the a complete evaluation of the colon by double-con- Canadian Cancer Society, the International Union trast barium enema or colonoscopy. Colonoscopy is against Cancer, and the U.S. Preventive Service Task preferred. An upper gastrointestinal evaluation should Force as yet have not (1, 4, 36, 52-55). In developing its be done ifthe results ofcolon studies are not significant. working guidelines, the NCI requested and obtained 6. Polyps found on sigmoidoscopy require histo- assistance from major medical organizations in the logical evaluation; ifthey are adenomatous the patient USA. Efforts were made to develop guidelines that needs complete evaluation of the colon for synchro- were reasonable and practical and which would help nous neoplastic lesions. practising physicians and patients select the most 7. These examinations should be done as part of appropriate approaches for early detection of cancer. comprehensive primary and secondary preventive Furthermore, the NCI indicated that the weight of measures in individuals during their medical check- evidence needed for proof of benefit is different for ups. case-finding and mass screening. 8. This approach should not be encouraged for The NCI has already noted that early detection healthy individuals in the general population who are and treatment were associated with a decreasing not seeking individual health check-ups until improved mortality rate from colorectal cancer, in spite of an mortality data become available. increasing incidence (52). Although the reasons for 9. This approach is reasonable for case-finding of these trends are unclear this may have resulted in part asymptomatic, early stage colon cancer and large from the utilization of techniques for earlier detection adenomatous polyps in the physician's office or surgery, and a greater attention to early symptoms and familial medical clinics and hospitals or as part of established risk factors. Physicians who utilize the best available cancer-related check-ups. It is justified by the interim data, concepts, technology, expert opinion, knowledge results ofongoing controlled screening studies and two ofthe disease, and clinicaljudgement may be having an decades of carefully monitored clinical application of impact on the natural history ofcolorectal cancer with the stool occult-blood test. improved outcome for a greater proportion of their Final results from these studies confirming reduced patients. mortality are needed before this approach can be Studies are currently under way to test the recommended to the health authorities and govern- hypothesis that a significant proportion of colorectal ments as a separate screening procedure for the general cancer is caused by a dominant gene with low pene- population. trance (11, 56, 57). Classification of the genetic basis of colorectal cancer and a better means of identifying high-risk patients would allow more effective applica- Research recommendations tion of screening and would help reduce major prob- lems of patients' acceptance of these preventive 1. Current trials evaluating the effect of stool- measures. blood tests on colorectal cancer mortality should be supported until completion. 2. Additional, new tests for screening of colorec- Recommendations for practice tal cancer and adenomas, including those that test 1. Men and women should be encouraged to specifically for blood and those that test for other seek medical check-ups. markers of colonic neoplasia, should be evaluated in 2. Persons with symptoms suggesting colorectal large controlled trials. neoplasia are not candidates for screening but should 3. New and improved collection devices need to be investigated for a diagnosis. be evaluated for the stool-blood test. 3. Asymptomatic individuals should have their 4. Factors related to patient acceptance of screen- risk evaluated to rule out inherited syndromes, in- ing need to be studied.

510 WHO Bulletin OMS. Vol. 68, 1990 Screening of average-risk Individuals for colorectal cancer

5. Factors related to physician application of lesquels la maladie a une forte probabilite de ceux screening and diagnostic testing need to be studied. chez lesquels cette probabilite est faible. 6. Mathematical modelling needs to be used with La sigmofdoscopie, particulierement quand new data that will be forthcoming to determine the elle est effectuee avec les longs endoscopes flexi- effects of screening by itself and in conjunction with bles, est capable de deceler approximativement evolving methods of primary prevention. 50% des cancers et des adenomes colorectaux. 7. Randomized trials with a mortality end-point L'efficacite de la sigmofdoscopie flexible en tant need to be considered regarding the value of flexible que test de depistage n'a pas ete bien etudiee sigmoidoscopy. dans des essais controles, mais divers rapports 8. Familial risk factors need to be examined indiquent que cet examen est bien accepte par les further to determine their value in helping to predict malades et qu'il permet une detection de la patients with a higher probability of developing ade- maladie a un stade plus favorable. La recherche nomas or cancer. de sang occulte dans les selles en utilisant des 9. The relative cost-effectiveness of flexible sig- lames impregnees de gafac a ete prouvee comme moidoscopy with double-contrast barium enema etant une methode possible dans diverses etudes; versus primary colonoscopy in the evaluation of elle permet de diagnostiquer de gros adenomes, et patients with a positive screening test needs to be donc de proceder ensuite a leur ablation mais elle examined. n'a probablement que peu de valeur en soi pour la 10. Colonoscopy needs to be studied as a screen- detection des petits adenomes, plus frequents. ing test in familial high-risk and average-risk indi- Actuellement, plus de 300000 sujets ont ete viduals. inclus dans des essais cliniques controles. Les donnees montrent un taux de positivite de 1-4% avec des lames non-hydratees, une valeur de prediction positive pour les adenomes et les can- cers d'environ 20-50%, le diagnostic plus precoce Acknowledgement des cancers, et une amelioration de la survie. La We are grateful to Dr A.B. Miller for a thoughfful review of sensibilite et la specificite etaient de 70% et 98%, this paper. respectivement. De nouveaux tests sont en cours d'evaluation, qui peuvent augmenter la sensibilite sans perte de specificite. Les resultats des etudes actuelles capables de prouver l'impact du depis- tage sur la mortalite par cancer colorectal sont R6sum6 attendus pour que cette methode soit consideree D6pistage des Individus A risque moyen de comme valable. L'evaluation diagnostique complete des cancer colorectal malades ayant un test de depistage positif est Le cancer colorectal se prete a des methodes de essentielle pour confirmer 1'efficacite du depistage car c'est une maladie suffisamment programme de depistage. La colonoscopie et repandue pour qu'elle soit d6tectee a un stade le lavement baryte a double contraste sont des precoce avec, ainsi de meilleures perspectives de methodes sensibles pour poser un diagnostic survie des malades. Un second b6n6fice possible precis de lesions du c6lon. La colonoscopie a une du d6pistage est lie a la decouverte et a l'ablation sensibilite plus grande pour le diagnostic de des adenomes pre-malins ayant pour consequence petites lesions et a egalement l'avantage de une diminution de l'incidence future du cancer permettre l'obtention de biopsies et l'ablation de colorectal. Certains malades peuvent etre con- polypes. L'acceptation des malades est d'une sider6s comme etant a haut risque parce qu'ils importance capitale pour la mise en ouvre de ces ont une colite ulc6reuse chronique sous-jacente strategies. Les calculs preliminaires de coOt/ ou des antecedents familiaux ou personnels de efficacite sont favorables. Actuellement, il est cancers ou d'adenomes colorectaux. Ces sujets raisonnable que des sujets asymptomatiques Ages demandent une surveillance speciale, plus etroite. de plus de 50 ans et a risque moyen aient une La majorite des individus sont "a moyen risque" recherche de sang dans les selles chaque annee pour la maladie s'ils sont ages de 50 ans (et plus), et une sigmofdoscopie flexible tous les 3-5 ans au age auquel l'incidence commence a augmenter titre de leurs soins medicaux normaux, et que ceux de fa9on significative. II faudrait disposer d'une dont le test est positif aient une colonoscopie. De m'thode de depistage basee sur des tests rapides, nouvelles donnees peuvent modifier ces recom- simples, capables de bien separer les sujets chez mandations a l'avenir. II est vraisemblable que de

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