CurrentStatusof FecalOccuR BloodTestingin Screening for ColorectalCancer

Transcription

1 CurrentStatusof FecalOccuR BloodTestingin Screening for ColorectalCancer Sidney J. Winawer, M.D. Martin Fleisher, Ph.D. Margaret Baldwin, M.P.A. Paul Sherlock, M.D. Introduction Colorectal cancer is one of the most prev alent cancers in western countries, ac counting for more than 120,000 cases each year in the United States alone.' This sta tistic, along with the high mortality rate of close to 60 percent, has stimulated in terest in new diagnostic approaches uti lizing recently developed concepts and techniques. In addition to average-risk Dr. Winawer is Chief of the Gastroenterology Service of the Department of Medicine of Me morial Sloan-Kettering Cancer Center, and Pro fessor of Clinical Medicine in the Department of Medicine of Cornell University Medical Col lege, in New York, New York. Dr. Fleisher is Attending Biochemist in the Department of Biochemistry of Memorial Sloan Kettering Cancer Center, and Assistant Profes sor of Biochemistry in the Sloan-Kettering In stitute Division of Cornell University Graduate School of Medical Sciences, in New York, New York. Ms. Baldwin is Research Administrator of Pre ventive Medicine Institute-Strang Clinic in New York, New York. Dr. Sherlock is Chairman of the Department of Medicine of Memorial Sloan-Kettering Cancer Center, and Professor and Vice Chairman of the Department of Medicine of Cornell University Medical College, in New York, New York. This work was supported in part by Public Health Service Research Grant CA from the National Cancer Institute through the Na tional Large Bowel Cancer Project. patientsâ men and women aged 40 and olderâ there are subgroups in the popu lation at increased risk for colorectat can cer (Table 1). These include patients with: â prior cured colorectal cancer â prior adenomas â ulcerative colitis, lasting more than seven years, involving the entire colon â history of female genital cancer â family history of one of the polyposis syndromes or one of the nonpolyposis, inherited colon cancer syndromes.2 Although much work needs to be done to further clarify these high-risk subgroups, especially those with familial factors, a much clearer picture exists today of those who are at increased risk for colorectal cancer compared with the average-risk population. Technological advances have also occurred recently: new methods for fecal occult blood testing, flexible sig moidoscopy, colonoscopy, and refinement of the double-contrast barium enema. A desirable goal based on these im provements is earlier diagnosis for im proved survival. This concept is in keeping with the current emphasis on preventive measures for cancer in general and for co lorectal cancer specifically. Prevention of colorectal cancer can be defined as primary or secondary. Primary prevention is the identification of factors, either genetic or environmental, respon sible for cotorectal cancer and its eradi cation. 100 CA-A CANCERJOURNALFORCLINICIANS

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4 @ Secondary prevention may be defined as early detection of colorectal cancer prior to its more advanced, devastating, and fa tal consequences, as well as detection and eradication of premalignant disease before its transformation into cancer. The goal in secondary prevention is to reduce the mor tality from colorectat cancer in the entire targeted group. This important concept must be distin guished from survival of patients identified as having a premalignant or malignant le sion. It is important to identify individuals with neoptastic lesions, and our goat, of course, is for these individuals to survive for a long time, free of disease. However, if this approach fails to identify a signifi cantly large number of people in this group, and they go on to develop their disease in the usual manner with the usual mortality, then the approach is a failure. Effective mortality reduction for cotorectal cancer for the population targeted by a sec ondary prevention approach requires meth ods that successfully identify at an early stage the majority of patients developing the disease. This should also be kept in mind when evaluating the results of pro For symptomatic patients, aggressive search of the colon could uncover premalignant adenomas, the removal of which can prevent the development of colorectal cancer. grams. Reports of improved survival in detected cases represent only one part of the overall picture.3 Secondary prevention of colorectal cancer includes three concepts: â Prompt recognition of symptoms that suggest colorectal cancer and application of aggressive diagnostic techniques. While it is preferable to make a diagnosis in the presymptomatic stage, there have been delays in diagnosing symptomatic patients. Prompt use of colonoscopy and barium enemas could probably reduce this delay for many patients. For patients with symp toms of colorectal neoplasia, aggressive search of the colon could uncover pre malignant adenomas; their removal can prevent the development of colorectal can cer. â The surgicalapproach:based on data from several centers, appropriate surgery in symptomatic patients has resulted in longer survival than that reported previ ously â Screening or case-finding techniques for asymptomatic patients. (Screening is used for a large population, and case find ing is for individual patients and small groups within the framework of the health care system.) These screening or case finding approaches should be varied, de pending on whether the patients are at av erage or high risk. Fecal Occult Blood Testing Background The testing of stool forthe presence of occult blood as an indicator of gastrointestinal can cer is an old concept. In the past, patients were given no dietary restrictions and asked to bring stool samples to be tested with guaiac solutions. There was no quality con trot of the stability of the reagents used. Be cause of the high percentage of false posi tives and false negatives, this approach was soon discarded. Benzidine was used in a similar manner, but it too was discarded, be cause of extremely high sensitivity that re sulted in a high percentage of false positives, with unnecessary diagnostic workups of pa tients. Hematest (ortho-totidine) was shown to be nonreproducible for clinical screen ing.6.7 Greegor reintroduced the guaiac test for occult blood in the stool in the late 1960s. While on a high-fiber, meat-free diet, patients were asked to smear two samples of stool per day for three days (for a total of six smears) onto a paper slide impregnated with guaiac. The slides were brought in for testing by a reagent of hy drogen peroxide in denatured alcohol. Co lorectal cancers were detected in several patients at an early pathological stage.8 VOL 32, NO. 2 MARCH/APRIL

5 The nature of the reaction of the guaiac test is not well understood. As currently utilized, the guaiac paper slide test consists of filter paper impregnated with guaiac, which undergoes phenolic oxidation in the presence of hemoglobin in the stool and hydrogen peroxide in the test reagent. The guaiac itself is a group of heterogenous compounds present in varying proportions and with different stages of purity, de pending on the processing of the guaiac before impregnation of the paper. The hemoglobin's positive reaction is a result of its pseudoperoxidase activity; hemoglobin interacts with hydrogen per oxide, resulting in phenotic oxidation of the guaiac, changing it to blue. Anything with peroxidase activityâ for example, fresh fruit and uncooked vegetablesâ can produce a positive reaction. Agents (such as ascorbic acid) that interfere with the oxidation reaction may produce a false negative reaction in the presence of hemo globin. A positive test, therefore, can be positive from nonhemoglobin peroxidases and be a false-positive test; can be positive from nonhuman hemoglobin present in foods such as meat; or can be positive from human hemoglobin lost as physiologic blood loss of no consequence, from benign lesions such as angiodysplasia and diver ticular disease, or from neoptastic lesions such as adenomas and cancers. Sufficient quantities of blood anywhere in the gas trointestinal tract can lead to a positive test.' Community Programs and Uncontrolled Trials Following Greegor's reintroduction of the occult blood test in the form of an im pregnated guaiac slide test, several studies and programs were initiated around the world to use this technique in screening for colorectal cancer. Initial observations were confirmed in studies in Hawaii by Glober and Pescoe, in the United States by Hastings and Miller, and in Germany by Gnauck and FrUhmorgen, confirming the concept that this test had potential use fulness in screening for colorectal cancer.7 Two control trials were initiated, one at Memorial Sloan-Kettering Cancer Center and the Preventive Medicine Institute-Strang Clinic, and another at the University of Minnesota. In addition to these two con trolled trials, several community pro grams, as well as uncontrolled trials, were started around the world (Table 2). In Greegor's original series, five per cent of the@patients had positive tests.8 In 47 cancers of the colon detected in a col laborative study organized by Greegor, 85 percent were considered to be pathologi cally localized to the bowel wall in patients who were truly asymptomatic; only 20 of 139 cases of cancer were within reach of the standard sigmoidoscope. â Â In Hastings' community-wide study of mass screening over a short period of time, five cases of colon cancer were discovered in the di agnostic workup of 41 patients with pos itive tests. In the study of 2,323 people by Miller and Knight, seven patients with polyps and three with cancer were identified in 39 patients who had positive slides and under went diagnostic examinations.7 In the Ha waiian study of Glober and Pescoe, out of 1,539 Japanese Americans, four asymp tomatic cancers and three polyps were de tected in the workup of 32 patients with positive tests. Gnauck's program, started in 1975, involved the participation of 5,016 persons in a newspaper-advertised campaign. In the positive group of 117 people, 13 carcinomas and numerous large polyps were found. Fruhmorgen's program included 5,007 patients. The rate of positive tests varied among his groups from 1.5 percent to 4.8 percent. In 144 of 202 patients, a complete diagnostic examination was per formed, yielding 22 carcinomas and 22 polyps larger than one cm in diameter.7 The frequency of positive slides in these studies ranged from one percent to six percent, and the predictive value for neoplasia (can cer or adenoma) varied from 18 percent to 50 percent. In a county-wide screening program, Bratow and Kopel reported a public re sponse twice as great as anticipated. The compliance rate in this study was 79 per cent; approximately 10 percent of the re 104 CA-A CANCERJOURNALFORCLINICIANS

6 turned slides had at least one positive specimen. Among the patients with positive testswho had diagnosticevaluation,15 percent were found to have polyps and nine percent were found to have cancers, which were early, localized lesions. This study demonstrated the feasibility of a commu nity-wide screening program. There was a problem with follow-up evaluation among patients, however, with only 30 percent of the individuals cooperating.7 The American Cancer Society has had keen interest in this area and has initiated several area-wide screening programs. ACS observed poor patient compliance for fecal occult blood testing (15 percent) unless public education was emphasized. In one such program, screening was allowed for those 21 years of age or older. Of 49,157 tests distributed, 19,707 (40 percent) were returned. Patients who had positive tests on an unrestricted diet had the test repeated on a restricted diet and were worked up only if the second test was positive.7 This approach was similar to Gnauck's and the Sarasota community program by Bralow. A total of 130 patients completed a diagnostic workup resulting in 101 with More data in the future from ongoing controlled trials are needed to determine whether screening results in a reduction in mortality for colorectal cancer. intestinal pathology, including 15 colorec tal cancers and 18 polyps. Compared with the Tumor Registry data in general for the area, the pathology of the cancers was fa vorable. In most community programs, such as this and the Sarasota program, the underlying difficulty appeared to be that physicians were not aware of the impor tance of thorough diagnostic evaluation of patients with positive tests on a single screening examination. Additional studies have been initiated in Japan by Kobayashi and his coworkers, in Israel by Rozen, and in Austria by Samec.7 A large, ambitious study has been started in the Federal Republic of West Ger many toencouragescreeningof asympto matic women and men in doctors' offices on a periodic basis with fecal occult blood testing. The program has already included several million people who have had fecal occult blood testing; some have had positive tests and further diagnostic evaluation. The study is now developing a data base and fol low-up for gathering results. Many varia tions of technique were used in the studies, but alt used the impregnated guaiac slide tests with stabilized reagent. A varying numberof samples were obtained from each patient in the various studies, with varying dietary restrictions. The presence or ab sence of symptoms was not always noted, and the population was often not well char acterized. Controlled Trials Two controlled clinical trials are studying the use of fecal occult blood testing in screening for colorectal cancer. The first, started in 1974 at Memorial Sloan-Ketter ing Cancer Center in collaboration with the Preventive Medicine Institute-Strang Clinic, includes asymptomatic men and women aged 40 and over coming to the Preventive Medicine Institute.â They receive a com prehensive medical examination including a questionnaire and rigid sigmoidoscopy. The study group was sent fecal occult blood tests to prepare at home within four days of their examination and bring in with them. Study patients were asked to prepare six smears over three days on a meat-free, high-fiber diet, with restriction of vitamins and medications. Patients were random ized by calendar period. After the slides were tested at exam ination, diagnostic tests were performed on the patients, including double-contrast barium enema and cotonoscopy if the slides were positive; an upper GI series was performed if no colonic neoplasm was found. Over 22,000 patients have been enrolled in this study, which is in a re screening and follow-up stage. The study's objective is to determine whether, based on an offering of fecal occult blood testing, VOL 32, NO. 2 MARCH/APRIL

7 colorectal cancermortalitycan be reduced in the studygroup as compared withthe control group. Compliance in the different subgroups ranged from 70 to 80 percent for fecal occult blood testing and 95 percent for sigmoidos copy. This high compliance, a result of the motivation of this population of self-re ferred patients, is in sharp contrast with the poor compliance in outreach programs without associated patient education. The overall rate of positive slides was 2.5 percent.butthisvarieddependingon thetypeof slidesused and patientstatus and age. Slide positivity was 1.7 percent at ages 40 to 49 and increased to 6.6 per cent for those over 70. The rate of posi tivity for the single Hemoccultx slides was one percent with a predictive value for neoplasia of 50 percent (12 percent for cancerand 38 percentforadenomas). With the Hemoccult Il slides, the rate of positivity increased to 3.7 percent with a predictive value of 44 percent. The pre dictive value increased with age (27 per cent at ages 40 to 49, to 52 percent at age over 70). Analysis of daily smears indi cated that only 41 percent of neoplastic lesions would have been detected if only one smear per day was examined rather than two smears. The predictive value did not correlate well with the number of pos itive slides. Colorectat cancer detected by slides had a more favorable pathologic staging as compared with those in the control group, and the detection by slides com plemented the detection by proctosig moidoscopy for colorectal cancers. A total of 71 colon cancers had been detected in the program at the time of the last report.â Overall, there were 59 cancers in the study group; 36 (61 percent) were detected by Hemoccult alone, and another seven (12 percent) were detected by both Hemoccult and proctoscopy. The remain ing 16 cases (27 percent) were detected by proctoscopy alone (eight) or symptoms leading to further diagnostic evaluation (eight). Of the total group of cancers, 32 were cases of prevalence and 27 were incidence cases. Overall, 59 percent of the preva lence and 74 percent of the incidence cases were staged in situ, Dukes' A, or Dukes' B. This compares with the 12 cancers in the control group detected by proctoscopy (six) or other means (six), for which both prevalence and incidence staging was only 33 percent in situ, Dukes' A, or Dukes' B. The double-contrast barium enema was highly sensitive for cancers, but had a low sensitivity for adenomas as compared with colonoscopy. A second controlled trial evaluating fecal occult blood testing was initiated at the University of Minnesota.'2 In this study. 48,000 participants were randomized into one of three study groupsâ those who re ceived Hemoccult slides each year, those who received slides every other year, and a control group. The overall rate of slide positivity was 2.4 percent. Persons found to have positive slides were requested to have diagnostic examinations, including x-rays and colon oscopy. The x-rays were single column, rather than double contrast. Of 873 patients with positive tests who underwent diag nostic evaluation, 72 (eight percent) had cancer of the colon or rectum, the majority (78 percent) of which were Dukes' A or B cancers. This study is now in a rescreening and follow-up stage. In this particular study, screening began at age 50, as compared with age 40 for the Memorial Sloan-Ket tering-strang Clinic study. The highest yield of neoplastic lesions was in patients 63 years of age or over, but this may be a factor of the older age of the patients entering this study. The sensitivity of the single-column barium enema was low, and colonoscopy was considered extremely important. Standardization of Reporting It is difficult to compare the results of the various screening programs because of in adequate reporting of patient characteris tics, types of slides used, interval between slide preparation and testing, type of diet used, and the presence or absence of qual ity control of slide testing. 106 CA-A CANCERJOURNALFORCLINICIANS

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9 In addition, the diagnostic workup var ied greatly: Some studies used sigmoidos copy, some single-column barium enemas, some the double-contrast technique, and still others cotonoscopy. There is a need for standardization. Uncontrolled trials and community programs are important in de termining the feasibility of these studies in terms of patient compliance, physician orientation and education, yield of diag nostic workup, staging of the cancers detected, and survival of the patients. Con trolled trials are needed to determine whether screening results in a mortality reduction for colorectal cancer. Another important question has to do with cost-ef fectiveness. Quality Control Many factors appear to influence fecal oc cult blood tests. Until recently, there has been no quality control, unless it was spe cifically set up in the laboratory using the test. A reference laboratory for fecal occult blood testing was established at Memorial Sloan-Kettering Cancer Center to serve as an international reference center for fecal occult blood testing.' Investigations in the reference laboratory have centered on sta bility, sensitivity, and reproducibility of the test. Studies on stability have shown a time dependent conversion of positive to neg ative Hemoccult slide results; this appears to be dependent on hemoglobin concentra tion. Crystalline human hemoglobin was dissolved in water as a primary standard to establish a criterion for sensitivity of the slide. This technique is reliable and can be reproduced in any testing laboratory. Studies indicate that the Hemoccult slide is sensitive to less than one mg/mt of hemoglobin in aqueous solution. Lab oratory studies also suggest that the Hem occult II slide is more sensitive than the single Hemoccult slide previously used. Rehydration alters the apparent sensitivity of the slides to hemoglobin. One of the reasons for this effect involved the disso lution of desiccated hemoglobin before the addition of the alcohol-developing reagent (Table 3). Hemoglobin, however, is not the only component reactivated following rehydra tion. Other interfering compounds, such as peroxidases present in bacteria and cer tain foods, are also rehydrated and hence interact to increase false-positive results. This one modification in test procedure is probably responsible for some of the var iation in positive detection rates reported from different studies. Our studies on the effects of rehydration indicate a significant increase in sensitivity of the Hemoccult slide following rehydration with water and buffer over a ph range of four to seven. Additional studies indicate that a strongly positive slide remains positive for at least 10 days, whether or not the slides are re hydrated with water or buffer. Initial weakly positive results may yield equiv ocal results on nonrehydrated slides after two to four days of storage. Sensitivity and Specificity The studies described thus far are related to the laboratory sensitivity of the slide test. An increase in laboratory sensitivity may result in increased clinical sensitivity with a greater detection of neoplastic le sions; it could also, however, result in more false-positive reactions because of the detection of more peroxidase activity in the stool, which would make the test less specific and therefore less effective as a screening test. We have observed that hydration of the Hemoccult II slide does increase clinical sensitivity but that false positivity is increased enough to be un acceptable for screening; it has, therefore, been eliminated within our program. Rehydration, however, is stilt being used in other programs, and comparisons of the nonrehydrated slide versus the re hydrated slide technique will have to be forthcoming. Studies from Australia'3 con firm the increased sensitivity of the slide seen in the laboratory and clinically as re ported from our program. These studies show that this increased sensitivity results in a greater detection rate of colorectal can cers, but there is also a high rate of false positivity. 108 CA-A CANCERJOURNALFORCLINICIANS

10 Further investigations from that group suggest that this high rate of false positivity resulting from rehydration of slides can be reduced by the use of a low peroxidase diet. If the rehydration technique is used, therefore, it should be accompanied by a strict, low peroxidase, meat-free, high-fi ber diet. The meat-free and high-fiber as pects of the diet have been less well stud ied. Before definite conclusions can be drawn, this will have to be tested further clinically in small group investigations as well as in field trials (Table 4). Tests Available Several products capable of detecting blood in the stool are commercially available to the international medical community. In the United States, Australia, and Europe. the Hemoccult slide test has received the greatest attention from the point of view of clinical and technical evaluation. Other slides currently available include the HemoFecÂ, Quik-CultÂ, Colo-RectÂ, HaemoscreenÂ, and CotoScreen (Table 5). Two fecal occult blood testing slides, one the Performance MonitorÂ, now have a quality control window. In addition to the guaiac and ortho-tolidine chemical tests for peroxidase activity, an immuno chemical test has been proposed that is specific for human hemoglobin; this elim inates the fatse-positivity factors from per oxidase activity caused by nonhuman hemoglobin and nonhemoglobin peroxi dases.'4 This test is more complex than the chemical fecat occult blood test, but if sim plified it may become a clinical consid eration in the near future. Guidelines for Use of Fecal Occult Blood Test Average-Risk Group How should the fecal occult blood test be utilized for screening? Should it be utilized in outreach screening or within the frame work of a comprehensive examination of patients already in the health care system? What techniques should be used for patient preparation of the slides? What slides should be used? How should the slides be tested? How should patients with positive VOL.32,NO.2 MARCH/APRIL

11 tests be worked up? If screening is to be initiated in average-risk individuals, at what age should it be initiated, to which of the high-risk groups would this ap proach be applicable, and how should it be integrated with other examinations such as sigmoidoscopy, colonoscopy, and x-ray studies? Both ACS'5 and the International Workgroup on Colorectal Cancer'6 have developed guidelines that address many of these questions. The International Work group felt that analysis of available data allowed the following recommendations to be made (analysis of new data will con tinue, which will provide a basis for mod ification of these recommendations): 1. If screening of individuals and small groups is to be promoted: â Persons at risk should be encouraged to enter the health care system. â Relative risk should be assessed by fam ily and personal history questionnaires. â Once patients are in the system, screen ing should be added to other aspects of medical evaluation. â Screening should include proctosig moidoscopy once every three to five years, beginning between the ages of 40 and 50. Rigid sigmoidoscopy should be used if this is the only available instru mentation, but flexible sigmoidoscopy, using a 60-cm scope by a trained en doscopist or a 30-cm scope by primary practicing physicians or paraprofession als, is preferred. â Screening should include fecal occult blood testing annually, beginning be tween the ages of 40 and 50. â Diagnostic workup of patients with a positive screening test should include colonoscopy. 2. Screening may be encouraged for individuals and small groups, but general or mass screening cannot be encouraged until firm mortality, risk, and cost data are available from ongoing programs. 3. Screening should be accompanied by programs to educate patients and make physicians more aware of the concepts and technology involved in screening, diag nosis, treatment, and follow-up. 4. Proper record-keeping and data collection should be part of any screening program. 5. Patients with a diagnosis of cob rectal neoplasia should be entered into a long-range follow-up surveillance program with periodic direct reexamination of the colon every three to five years. 6. The reference laboratory at Me morial Sloan-Kettering Cancer Center should be used for quality control of fecal occult blood tests. Current and new slides should be submitted for evaluation. 7. The program questionnaire, as re vised by the Workgroup, should be used to standardize methods of reporting clini cal data, to characterize different screening programs, and to provide information to other centers. Questionnaires should be kept in a repository in the reference lab oratory at Memorial Sloan-Kettering Can cer Center. 8. Based on their evaluation in the reference laboratory and in clinical pro grams, specific fecal occult blood tests should be used in screening. ACS recommends that patients over the age of 40 have a digital rectal exami nation annually. The stool guaiac test should be added at age 50 on an annual basis, with a sigmoidoscopy every three to five years after two initial negative sig moidoscopies one year apart. The rationale for these is that, although no single study proves the value of any particular test, there is strong suggestive evidence from several sources that detect ing colon cancer prior to the onset of signs and symptoms will prolong survival. The earlier Dukes' staging detected in asymp tomatic patients being screened with fecal occult blood testing appears to be similar to that seen in screening programs utilizing proctosigmoidoscopy. It is felt that the long-term survival following detection by slides will be sim ilar to that seen after screening with proc tosigmoidoscopy. This remains to be seen, of course. The screening programs with the stool guaiac slide tests have not gone on long enough to provide conclusive evi dence, and until such evidence is present, 110 CA-A CANCERJOURNALFORCLINICIANS

12 as welt as evidence of a mortality benefit and cost-effectiveness, neither ACS, the International Workgroup, nor the National Cancer Institute are prepared to recom mend mass screening with the guaiac slide test. Both ACS and the International Workgroup recommend that this test be added only when a patient is already in the health care system.'7 High-Risk Groups These recommendations relate to average risk patients. Patients who have already undergone surgery and have been cured of colorectal cancer, as well as those with prior colonoscopic polypectomy, should have their colons cleared of additional syn chronous lesions (these occur in 40 percent to 50 percent of patients) directly, radio logically and endoscopically, initially and at periodic intervals following treatment. It is possible that fecal occult blood testing may have a rote as an interval ex amination in such high-risk groups. This is currently being studied within the frame work of the National Polyp Study'8 with patients randomized after cobonoscopic polypectomy into more aggressive and less aggressive arms. Within each group, the barium enema, colonoscopy, and fecal oc cult blood tests are being evaluated for sen sitivity and specificity. In that study, predictive factors are being examined related to the natural history of subsequent ade nomas of various histological types in the patients entered. Fecal occult blood testing may have some role in the nonpolyposis, inherited colon cancer syndromes. Patients with au tosomal dominant modes of inheritance in striking family histories should be directly examined by x-ray or cobonoscopy at pe riodic intervals. Fecal occult blood testing could serve as an interval exam. Patients with a suggestive family history, but not one of an autosomal dominant form, could have fecal occult blood testing and perhaps proctosigmoidoscopy performed begin ning in their 20s when their risk begins. Fecal occult blood testing has no role in patients with familial polyposis or ulcer ative colitis, since they have lesions that may produce positivity without the pres ence of cancer (Table 6). Patient Compliance and Physician Education Patient compliance during screening pro grams has been excellent when the patients have been welt motivated. Those tacking the appropriate orientation and education, however, have had extremely poor com pliance. It has also been observed that primary care physicians, who would be heavily in volved in case finding, screening, diag nosis, and follow-up of such patients, are not thoroughly acquainted with these techniques nor with the natural history of adenomas and cotorectat cancer. For case finding and screening programs to be suc cessful, educational programs must be de veloped and presented to both the medical community and the lay public. Conclusion As yet, there are no controlled studies that demonstrate the value of the stool guaiac slide test. Several studies do show that the test can detect cancers in an early stage. Coupled with the results of other studies that indicate a reduction in mortality as sociated with earlier detection, the rec ommended approach appears reasonable. It should be kept in mind, however, that the available data are as yet inconclusive, that these recommendations should be con sidered only as guidelines to be tailored to the needs of individual people and pro grams, and that the evidence of benefits as welt as potential risks and costs needs to be further ascertained before the tests are widely used.'5 VOL. 32, NO. 2 MARCH/APRIL

13 References I. Cancer Facts and Figures, New York, American Cancer Society Inc Winawer SJ, Sherlock P, Schottenfetd D, et at: Screening for colon cancer. Gastroenter otogy 70:783â 789, Winawer SJ: Screening for colorectat can cer: an overview. Cancer 45:1093â 1098, EnkerWE, LafferUT, BlockGE: Enhanced survival of patients with colon and rectal cancer is based upon wide anatomic resection. Ann Surg 190:350â 360, SteamsMW Jr:Adenocarcinoma, instearns MW Jr (ed): Neoplasms of the Colon, Rectum, and Anus. New York, John Wiley & Sons mc, 1980, pp 79â Ostrow JD, Mulvaney CA, Hansel JR. et al: Sensitivity and reproducibility of chemical tests for fecal occult blood with an emphasis on false positive reactions. Am J Dig Dis 18:930â 940, Winawer Si, Andrews M, Miller CH, et at: Review of screening for colorectal cancer using fecat occult blood testing, in Winawer Si, Schottenfeld D, Sherlock P (eds): Progress in Cancer Research and Therapy, vol 13. Cob rectal Cancer: Prevention, Epidemiology, and Screening. New York, Raven Press, 1980, pp 249â Greegor DH: Diagnosis of large bowel can cer in the asymptomatic patient. JAMA 201:943â 945, Fleisher M, Schwartz MK, Winawer Si: Laboratory studies on the Hemoccult slide for fecat occult blood testing, in Winawer Si, Schottenfeld D, Sherlock P (eds): Progress in Cancer Research and Therapy, vol 13. Cob rectal Cancer: Prevention, Epidemiology, and Screening. New York, Raven Press, 1980, pp 181â Greegor DH: Detection of coborectal cancer using guaiac slides. CA 22:360â 363,1972. It. Winawer Si, Andrews M, Flehinger B, et al: Progress report on controlled trial of fecal occult blood testing for the detection of cob rectal neoplasia. Cancer 45:2959â 2964, Gilbertsen VA, McHugh R, Schuman U, et al: The earlier detection of coborectal cancers: a preliminary report of the results of the occult blood study. Cancer 45:2899â 2901, Macrae FA, St. John DJB: Colorectal can cer (CRC) screening: relationship between pat terns of bleeding and Hemoccult II (HO) sensitivity, abstracted. Gastroenterotogy 80(pt 2):1220, Songster CU, Barrows OH, iarrett DD: Im munochemicat detection of human fecat occult blood, in Winawer Si, Schottenfeld D, Sher lock P (eds): Progress in Cancer Research and Therapy, vol 13. Coborectal Cancer: Preven tion, Epidemiology, and Screening. New York, Raven Press, 1980, pp 193â Eddy DM: Guidelines for the cancer-re lated checkup: recommendations and rationale. CA (special issue), vol 30, July/August Report of the International Workgroup on Colorectal Cancer, Geneva, January Winawer Si: Coborectal cancer screening and early diagnosis, in Brodie DR (ed): Screen ing and Early Detection of Coborectal Cancer. Consensus Development Conference Proceed ings. NIH Publication No , 1979, pp 193â Winawer Si, Stewart E, Gottlieb U, et at: Nationat Polyp Study: organization and state ment of purpose, abstracted. Gastroenterology 80(pt 2):l3l6, CA-A CANCERJOURNALFORCLINICIANS