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Colon cancer screening

Colon cancer screening 10 Multidisciplinary Symposium — screening for cancer spiral computed tomography scanner. Br J Cancer 2001; 84: [18] Reeves AP, Kostis WJ. Computer-aided diagnosis of small 25. pulmonary nodules. Sem Ultrasound, CT & MRI 2000; 2: [16] ImPACT CT Scanner Comparison Report Issue 12 MDA/00/ The digital object identifier for this article is: 10.1102/ [17] Living with Radiation. NRPB 1998; ISBN 0-85951-419-6; 73: 1470-7330.2001.006 Jay P Heiken Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA Colorectal cancer is a major health problem worldwide. Table 1 Recommended options for colorectal cancer Last year in the United States alone, more than 130 000 screening in asymptomatic, average-risk individuals* people were diagnosed with colorectal cancer and more [1] Starting at age 50 than 56 000 died of their disease . Fortunately, this Annual FOBT† neoplasm is highly suited to screening because of its long Flexible sigmoidoscopy every 5 years preclinical phase, during which it is detectable and Annual FOBT and sigmoidoscopy every 5 years [2] curable . Nevertheless, screening programs for colorec- Colonoscopy every 10 years tal cancer have been only partly successful, owing Double-contrast barium enema every 5–10 years largely to poor patient compliance with screening rec- [3,4] ommendations . A number of organizations including *Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; the World Health Organization (WHO), the American 112: 594–642. Cancer Society (ACS), the Agency for Health Care †The American Cancer Society does not recommend fecal occult Policy and Research (AHCPR), the US Preventive blood testing (FOBT) by itself. Service Task Force (USPSTF), and the American Gastroenterology Association (AGA) have issued or endorsed guidelines for colorectal cancer screening. This review summarizes the clinical evidence supporting Fecal occult blood testing colorectal cancer screening in the average-risk popula- Fecal occult blood testing (FOBT) is the safest and tion and in high-risk groups, discusses the advantages least expensive of the currently available screening and disadvantages of the available screening tests, and tests. Three prospective, randomized, controlled trials outlines the currently recommended guidelines for have demonstrated the effectiveness of FOBT in screening based on risk category. [7–9] reducing colorectal cancer mortality by 15% to 33% . However, its benefit in reducing colorectal mortality is attributed not only to early cancer detection but also to the incidental discovery and removal of adenomatous Average-risk population polyps at subsequent colonoscopy. Such chance discov- Average-risk patients are asymptomatic individuals aged ery of adenomatous polyps and non-bleeding cancers by 50 years of age or older who have no personal or family colonoscopy has been estimated to account for 16–25% history of colorectal cancer or adenomatous polyps and of the colorectal cancer deaths prevented by the use of [10] no history of inflammatory bowel disease. The two most FOBT . Limitations of FOBT include its relatively recently published screening recommendations, those of low sensitivity for detecting cancers and its inability to [5] [6] [11] the ACS and AHCPR , present guidelines for screen- detect the vast majority of adenomas . Because colo- ing average-risk patients in the form of lists of options rectal cancers bleed intermittently, 50% or more of (Table 1). The options include annual fecal occult blood patients with colorectal cancer may have a negative [11,12] test (not included as a stand alone test in the ACS test result . Thus, to be effective, FOBT must be guidelines), flexible sigmoidoscopy every 5 years, annual administered annually or biennially, which makes fecal occult blood test plus flexible sigmoidoscopy every patient compliance a problem. Furthermore, the positive 5 years, double-contrast barium enema every 5 to 10 predictive value of FOBT is only approximately [11,12] years, and colonoscopy every 10 years. 10% . Multidisciplinary Symposium — screening for cancer 11 Flexible sigmoidoscopy Barium enema examination Because of its higher sensitivity than single contrast Data from two case–control studies support the effec- barium enema, double-contrast barium enema is consid- tiveness of flexible sigmoidoscopy in reducing colorectal [13,14] ered the current radiologic alternative to colonoscopy cancer mortality . Individuals in these studies who for colorectal cancer detection. Similar to colonoscopy, had undergone at least one screening sigmoidoscopy barium enema examination is a test that allows evalu- during the previous 10 years had only a 21% to 30% risk ation of the entire colon in approximately 90–95% of of developing fatal colorectal cancer as control subjects. [29–31] patients . No data are available on the sensitivity of Compared with colonoscopy, flexible sigmoidoscopy double-contrast barium enema in a screening popula- is less expensive and has a lower complication rate tion. In patients undergoing diagnostic examinations, (approximately one to two perforations per 10 000 ex- [6,15] the reported sensitivity of this test for the detection of aminations) . In addition, it requires a less rigorous [32–34] cancer is 85–90% , and the sensitivity for adenomas bowel preparation and does not require sedation. The [35,36] larger than 1 cm is 75–90% . However, recently major disadvantage of flexible sigmoidoscopy, however, published data from the National Polyp Study in the is that it examines only a portion of the colon, thereby United States demonstrated a sensitivity for double- enabling detection of only approximately 50% of colonic [16,17] contrast barium enema of only approximately 50% for lesions . If a polyp is detected by sigmoidoscopy, polyps 1 cm or larger in patients undergoing surveillance colonoscopy is still needed to evaluate the entire colon. [37] after removal of adenomatous polyps . Advantages of double-contrast barium enema compared with colon- oscopy are that it is safer (approximately one perfora- Fecal occult blood testing combined with [38] tion in 25 000 procedures) , less expensive, and does flexible sigmoidoscopy not require sedation. Its major disadvantages are its The rationale for combining FOBT with flexible sig- lower sensitivity and the inability to remove polyps, thus moidoscopy is two-fold: (1) approximately half of the requiring colonoscopy or sigmoidoscopy after positive cancers missed by FOBT would be detected at sig- examinations. moidoscopy, and (2) FOBT is insensitive for detecting adenomas, many of which would be detected at sig- moidoscopy. Nevertheless, there is little direct evidence Computed tomography (CT) colonography to support such a combined approach. Furthermore, a CT colonography (also known as ‘virtual colonoscopy’) large number of colonic adenomas and carcinomas are is a relatively new radiologic procedure that holds not within reach of the sigmoidoscope. Although some promise as a colorectal cancer-screening test, but of these lesions would be detected when a positive requires further evaluation. In this study a helically sigmoidoscopy leads to a follow-up colonoscopy or acquired volumetric data set of the abdomen and pelvis barium enema, many of them would be missed, as up to is obtained after insufflation of the colon with air or 50% of proximal colonic cancers are not associated with [18–22] carbon dioxide. The colon can then be viewed with a distal adenoma . either 2-dimensional or 3-dimensional techniques. The 3-dimensional visualization technique provides a per- spective that simulates colonoscopic navigation of the Colonoscopy colonic lumen. Prospective studies performed in selected Colonoscopy is the only colorectal cancer screening test groups of high-risk patients have reported sensitivities that allows evaluation of the entire colon and provides with CT colonography of 50% to 91% for polyps 1 cm or the opportunity to remove polyps and small polypoid [39–43] larger . It is important to note, however, that the cancers at the same time. Although there are no con- results of such studies cannot be generalized to a screen- trolled trials demonstrating that screening colonoscopy ing population of average-risk individuals. One potential reduces colorectal cancer incidence or mortality in advantage of CT colonography is the possibility of those at average risk for the disease, indirect evidence avoiding rigorous bowel preparation through the use of for the effectiveness of colonoscopy comes from one barium stool tagging and electronic subtraction of stool [15] case–control study and uncontrolled observational from the colon prior to diagnostic evaluation of the [23–25] studies . The case–control study showed a 40% to [44] images . Whether CT colonography will become a 50% reduction in colorectal cancer incidence in individ- viable alternative to colonoscopy for colorectal cancer uals who had undergone colonoscopy or polypec- screening remains to be seen. [15] tomy . A limitation of colonoscopy is that it is [18,19,26] incomplete in 5–15% of patients . In addition, colonoscopy is associated with the highest risk of com- Cost-effectiveness plications of all screening tests. Perforation occurs in approximately 1 in 1000 colonoscopies, major bleeding Most studies of the cost-effectiveness of FOBT (every 1 occurs in approximately 3 per 1000, and one to three to 2 years), flexible sigmoidoscopy (every 5 years), patients undergoing colonoscopy die of complications colonoscopy (every 10 years) and double-contrast [6,19,26–28] from the procedure . barium enema examination (every 5 to 10 years) have 12 Multidisciplinary Symposium — screening for cancer Table 2 Recommendations for colorectal cancer screening in individuals at increased risk* First-degree relative with colorectal cancer or adenomatous polyp(s): same as for average risk individual, but begin at age 40 Family history of FAP Genetic counseling (consider genetic testing) Annual flexible sigmoidoscopy beginning at puberty if gene carrier or indeterminate Family history of HNPCC Genetic counseling (consider genetic testing) Colonoscopy every 1–2 years beginning at age 20–30, annually beginning at age 40 History of inflammatory bowel disease Consider colonoscopy surveillance for dysplasia every 1–2 years beginning after 8 years of disease for pancolitis and after 15 years of disease for left-sided colitis *Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; 112: 594–642. FAP, familial adenomatous polyposis; HNPCC, hereditary nonpolyposis colorectal cancer. shown costs per life-year saved ranging from approxi- colitis are also at increased risk for colorectal cancer, but mately $2000 to $15 000 for FOBT up to $22 000 for the risk is lower than that associated with ulcerative [45–48] [55] colonoscopy . These figures compare favorably with colitis . Familial adenomatous polyposis coli (FAP) is estimates of cost per life-year saved for breast cancer, a disease that results from inherited or acquired defects cervical cancer and hypertension screening programs, in the APC gene located on the fifth chromosome. [49–50] which range from approximately $9000 to $50 000 . Patients with this disease develop numerous polyps throughout the colon, which results in a 100% risk of colorectal cancer if the colon is not removed. Hereditary nonpolyposis colorectal cancer (HNPCC) is an auto- Screening recommendations (Table 1) somal dominant disorder that results in a familial pre- Recommended options for colorectal cancer screening disposition to multiple cancers. The colon cancers of asymptomatic individuals of average risk include the typically occur at a young age, are often located in the following (beginning at age 50): annual FOBT (if right colon, and may be associated with extracolonic [56] positive, examine entire colon with colonoscopy or neoplasms . double-contrast barium enema examination), flexible sigmoidoscopy every 5 years (followed by colonoscopy if adenomatous polyp or cancer found), annual FOBT and Screening recommendations (Table 2) sigmoidoscopy every 5 years, colonoscopy every 10 For individuals with first-degree relatives with colo- years, or double-contrast barium enema examination rectal cancer or an adenomatous polyp, the screening every 5–10 years. It should be noted that the American recommendations are the same as for the average risk Cancer Society does not endorse the option of FOBT by population, except that screening should begin at age 40. itself because of the relatively low mortality reductions [5] (Patients with a personal history of colorectal cancer or that have been associated with its use . adenomatous polyp are not included in this discussion, as they fall under the category of surveillance rather than screening.) The recommendation for patients with High-risk population FAP is to receive genetic counseling (and possibly Individuals at increased risk for colorectal cancer are genetic testing to determine if the patient is a gene those with: (1) a personal or family (first degree relative) carrier) and to undergo flexible sigmoidoscopy annually history of colorectal cancer or adenoma; (2) longstand- beginning at puberty. The recommendation for patients ing ulcerative or Crohn’s colitis; or (3) a genetic predis- with HNPCC is to receive genetic counseling (and position to a hereditary polyposis or nonpolyposis possibly genetic testing) and to undergo colonoscopy syndrome. Individuals with a single first-degree relative every 1–2 years beginning at age 20–30, with annual with colorectal cancer have a risk of developing colo- colonoscopies beginning at age 40. The recommendation rectal cancer approximately 1.7 times that of the general for patients with longstanding ulcerative colitis is to [51] population . In addition, cancers tend to occur at an undergo colonoscopy with biopsies looking for dysplasia earlier age in this population. First-degree relatives of every 1–2 years beginning 8 years after diagnosis for patients with adenomas have a similar increased risk pancolitis and beginning 15 years after diagnosis for [52,53] of colorectal cancer . Patients with long-standing left-sided disease. However, there is no direct evidence ulcerative colitis are at increased risk for colorectal that this practice reduces colorectal cancer mortality in cancer, particularly those with pancolitis and early age these patients and none that it is more effective than [54] [6] of onset of their disease . Colorectal cancer in this colectomy based on extent and duration of disease . group of patients is thought to develop in areas of Surveillance for colorectal cancer is not currently [57] mucosal dysplasia. Patients with longstanding Crohn’s recommended for patients with Crohn’s colitis . Multidisciplinary Symposium — screening for cancer 13 [24] Jøgensen OD, Kronborg O, Fenger C. The Funen adenoma References follow-up study: Incidence and death from colorectal [1] Greenlee RT, Murray P, Bolden S, Wingo PA. Cancer carcinoma in an adenoma surveillance program. Scand J statistics: 2000. CA Cancer J Clin 2000; 50: 7–33. Gastroenterol 1993; 28: 869–74. [2] Bond JH. 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Cancer Society Detection and Treatment Advisory Group on [29] Bloomfield JA. Reliability of barium enema in detecting Colorectal Cancer. CA Cancer J Clin 1997; 47: 154–60. colonic neoplasia. Med J Austr 1981; 1: 631–3. [6] Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer [30] Jaramillo E, Slezak P. Comparison between double-contrast screening: clinical guidelines and rationale. Gastroenterology barium enema and colonoscopy to investigate lower gastroin- 1997; 112: 594–642. testinal bleeding. Gastrointest Radiol 1992; 17: 81–3. [7] Mandel JS, Bond JH, Church TR et al. Reducing mortality [31] Brewster NT, Grieve DC, Saunders JH. Double-contrast from colorectal cancer by screening for fecal occult blood. barium enema and flexible sigmoidoscopy for routine colonic Minnesota Colon Cancer Control Study. N Engl J Med 1993; investigation. Br J Surg 1994; 8: 445–7. 328: 1365–71. [32] Rex DK, Rahmani EY, Haseman JH et al. Relative sensitivity [8] Kronborg O, Fenger C, Olsen J et al. 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[38] Blakeborough A, Sheridan MB, Chapman AH. Complica- [14] Newcomb PA, Norfleet RG, Storer BE et al. Screening tions of barium enema examinations: a survey of UK consult- sigmoidoscopy and colorectal cancer mortality. J Natl Cancer ant radiologists 1992–1994. Clin Radiol 1992; 52: 142–8. Inst 1992; 84: 1572–5. [39] Hara AJ, Johnson CD, Reed JE et al. Detection of colorectal [15] Muller AD, Sonnenberg A. Prevention of colorectal cancer by polyps with CT colography: initial assessment of sensitivity flexible endoscopy and polypectomy: a case-control study of and specificity. Radiology 1997; 205: 59–65. 32 702 veterans. Ann Intern Med 1995; 123: 904–10. [40] Fenlon HM, Nunes DP, Schroy PC et al. A comparison of [16] Selby JV, Friedman GD. US preventative task force. virtual and conventional colonoscopy for the detection of Sigmoidoscopy in the periodic health examination of colorectal polyps. N Engl J Med 1999; 341: 1496–503. asymptomatic adults. JAMA 1989; 261: 594–601. [41] Kay CL, Kulling D, Hawes HR, Young JWR, Cotton PB. [17] Selby JV, Friedman GD, Collen MF. Sigmoidoscopy and Virtual endoscopy — comparison with colonoscopy in the mortality from colorectal cancer: the Kaiser Permanente detection of space-occupying lesions of the colon. Endoscopy Multiplastic Evaluation study. J Clin Epidemiol 1988; 41: 2000; 32: 226–32. 427–34. [42] Rex DK, Vining D, Kopecky KK. An initial experience with [18] Lieberman DA, Smith FW. Screening for colon malignancy screening for colon polyps using spiral CT with and without with colonoscopy. Am J Gastroenterol 1991; 86: 1775–80. CT colography (virtual colonoscopy). Gastrointest Endosc [19] Rex DK, Lehman GA, Hawes RH et al. Screening colonos- 1999; 50: 309–13. copy in symptomatic average-risk persons with negative fecal [43] Yee J, Akerkar GA, Hung RK et al. Colorectal neoplasia: occult blood tests. Gastroenterology 1991; 100: 64–7. performance characteristics of CT colonography for detection [20] Kadakia SC, Wrobleski CS, Kadakia AS et al. Prevalence or in 300 patients. Radiology 2001; 219: 685–92. proximal colonic polyps in average-risk asymptomatic [44] Callstrom MR, Johnson CD, Fletcher JG et al.CT patients with negative fecal occult blood test and flexible colonography without cathartic preparation: feasibility study. sigmoidoscopy. Gastrointest Endosc 1996; 44: 112–7. Radiology 2001; 219: 693–8. [45] Eddy DM. Screening for colorectal cancer. Ann Intern Med [21] Lemmel TG, Haseman JH, Rex DK et al. Neoplasia distal to 1990; 113: 373–84. the splenic flexure in patients with proximal colon cancer. Gastrointest Endosc 1996; 44: 109–11. [46] Glick S, Wagner JL, Johnson CD. Cost-effectiveness of [22] Imperiale TF, Wagner DR, Ching YL, Larkin GN, Rogge JD, double-contrast barium enema in screening for colorectal Ransohoff DF. Risk of advanced proximal neoplasms in cancer. Am J Radiol 1998; 170: 629–36. asymptomatic adults according to the distal colorectal [47] Gyrd-Hansen D. Fecal occult blood tests: a cost-effectiveness findings. N Engl J Med 2000; 343: 169–74. analysis. Int J Technol Asses Health Care 1998; 14: 290–301. [23] Winawer SJ, Zauber AG, Ho MN et al. Prevention of [48] Whynes DK, Nielson AR, Walker AR et al. Fecal occult colorectal cancer by colonoscopic polypectomy. N Engl J Med blood screening for colorectal cancer: is it cost-effective? 1977; 329: 1977–81. Health Econ 1998; 7: 21–9. 14 Multidisciplinary Symposium — screening for cancer [49] Garber AM, Phelps CE. Economic foundation of cost- [54] Ekbom A, Helmick C, Zack M et al. Ulcerative colitis and effectiveness analysis. J Health Econ 1997; 16: 1–31. colorectal cancer. A population-based study. N Engl J Med [50] Brown ML, Fintor L. Cost-effectiveness of breast cancer 1990; 323: 1228–33. screening: preliminary results of a systematic review of the [55] Ekbom A, Helmick C, Zack M et al. Increased risk of literature. Breast Cancer Res Treat 1993; 25: 113–8. large-bowel cancer in Crohn’s disease with colonic [51] Fuchs CS, Giovannucci EL, Colditz G. A prospective study of involvement. Lancet 1990; 336: 357–9. family history and the risk of colorectal cancer. N Engl J Med [56] Vasen HF, Wijnen JT, Menko FH et al. Cancer risk in 1994: 331: 1669–74. families with hereditary non-polyposis colorectal cancer diag- [52] Ahsan H, Neugut AI, Garbowski CG et al. Family history nosed by mutation analysis. Gastroenterology 1996; 110: of colorectal adenomatous polyps and increased risk for 1020–7. colorectal cancer. Ann Intern Med 1998; 128: 900–5. [57] Helm JF, Sandler RS. Colorectal cancer screening. Med Clin [53] Winawer SJ, Zauber AG, Gerdes H et al. Risk of colorectal N Am 1999; 83: 1403–22. cancer in the families of patients with adenomatous polyps. The digital object identifier for this article is: 10.1102/ National Polyp Study Workgroup. N Engl J Med 1996; 334: 82–7. 1470-7330.2001.008 Ovarian cancer screening B Rufford, U Menon and I Jacobs Gynaecology Cancer Research Unit, St Bartholomew’s and the Royal London Medical and Dental School, London, UK Introduction What to screen for A screening programme should ideally be based on the Ovarian cancer is the most common gynaecological detection of a pre-malignant condition in order to lower malignancy in the developed world. It also carries the disease incidence and maximize mortality reduction, as worst prognosis with an overall 5-year survival of 30%. is the case with the cervical screening programme. This is likely to be due to the disease frequently present- Although it is suggested that inclusion cysts and benign ing late, the ovary position within the peritoneal cavity and borderline ovarian tumours may be pre-malignant, resulting in minimal local irritation, or interference with this remains speculative. Crayford et al. recently ana- vital structures until ovarian enlargement is consider- lysed follow-up data from an ovarian cancer screening able, or metastasis occurs. Seventy per cent of women trial to assess whether removal of persistent ovarian are diagnosed with stage III or IV disease, with 5-year cysts was associated with a reduction in mortality from [1] survivals of 15–20% and less than 5%, respectively . [3] ovarian cancer . No such reduction was found relative Despite an increase in understanding of the molecular to other cancers, although it is difficult to interpret the events underlying malignancy, and advances in both findings in the absence of a control group, and incidence surgery and chemotherapy, the overall prognosis of may have been a more appropriate end-point than ovarian cancer has changed little over the last 30 years. mortality. In the absence of confirmed pre-malignant However, women who are diagnosed at an early stage do change, screening for ovarian cancer is directed at have a significantly improved prognosis, with survival of present to the detection of pre-clinical disease. above 80% in stage I disease, and above 90% in those [2] diagnosed at stage Ia . The best way of improving outcome may be, therefore, to detect the condition at an What is required from a screening test early stage, when the prognosis remains relatively good, via a screening programme. This is an exciting prospect A suitable screening test requires both high sensitivity and screening trials have shown some encouraging and specificity. Women who have a positive screen results. However, as yet screening has not been shown require further investigation, often in the form of ex- conclusively to reduce mortality from ovarian cancer. In ploratory surgery. It is therefore imperative to maximize addition, our lack of knowledge about disease progres- specificity in order to obtain a high positive predictive sion and of primary peritoneal cancer, as well as the value, and decrease the number of false-positive screens. possible surgical and psychological morbidity that may In the general population, a specificity of 99.6% is result from screening, should be considered. There are required to achieve a positive predictive value of [4] also, of course, cost implications. 10% , i.e. to limit the number of unnecessary surgical http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Cancer Imaging Springer Journals

Colon cancer screening

Heiken, Jay
Cancer Imaging , Volume 2 (1) – May 5, 2015
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Springer Journals
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Copyright © 2001 by International Cancer Imaging Society
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Medicine & Public Health; Imaging / Radiology; Cancer Research; Oncology
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Abstract

10 Multidisciplinary Symposium — screening for cancer spiral computed tomography scanner. Br J Cancer 2001; 84: [18] Reeves AP, Kostis WJ. Computer-aided diagnosis of small 25. pulmonary nodules. Sem Ultrasound, CT & MRI 2000; 2: [16] ImPACT CT Scanner Comparison Report Issue 12 MDA/00/ The digital object identifier for this article is: 10.1102/ [17] Living with Radiation. NRPB 1998; ISBN 0-85951-419-6; 73: 1470-7330.2001.006 Jay P Heiken Mallinckrodt Institute of Radiology, Washington University School of Medicine, St Louis, Missouri, USA Colorectal cancer is a major health problem worldwide. Table 1 Recommended options for colorectal cancer Last year in the United States alone, more than 130 000 screening in asymptomatic, average-risk individuals* people were diagnosed with colorectal cancer and more [1] Starting at age 50 than 56 000 died of their disease . Fortunately, this Annual FOBT† neoplasm is highly suited to screening because of its long Flexible sigmoidoscopy every 5 years preclinical phase, during which it is detectable and Annual FOBT and sigmoidoscopy every 5 years [2] curable . Nevertheless, screening programs for colorec- Colonoscopy every 10 years tal cancer have been only partly successful, owing Double-contrast barium enema every 5–10 years largely to poor patient compliance with screening rec- [3,4] ommendations . A number of organizations including *Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; the World Health Organization (WHO), the American 112: 594–642. Cancer Society (ACS), the Agency for Health Care †The American Cancer Society does not recommend fecal occult Policy and Research (AHCPR), the US Preventive blood testing (FOBT) by itself. Service Task Force (USPSTF), and the American Gastroenterology Association (AGA) have issued or endorsed guidelines for colorectal cancer screening. This review summarizes the clinical evidence supporting Fecal occult blood testing colorectal cancer screening in the average-risk popula- Fecal occult blood testing (FOBT) is the safest and tion and in high-risk groups, discusses the advantages least expensive of the currently available screening and disadvantages of the available screening tests, and tests. Three prospective, randomized, controlled trials outlines the currently recommended guidelines for have demonstrated the effectiveness of FOBT in screening based on risk category. [7–9] reducing colorectal cancer mortality by 15% to 33% . However, its benefit in reducing colorectal mortality is attributed not only to early cancer detection but also to the incidental discovery and removal of adenomatous Average-risk population polyps at subsequent colonoscopy. Such chance discov- Average-risk patients are asymptomatic individuals aged ery of adenomatous polyps and non-bleeding cancers by 50 years of age or older who have no personal or family colonoscopy has been estimated to account for 16–25% history of colorectal cancer or adenomatous polyps and of the colorectal cancer deaths prevented by the use of [10] no history of inflammatory bowel disease. The two most FOBT . Limitations of FOBT include its relatively recently published screening recommendations, those of low sensitivity for detecting cancers and its inability to [5] [6] [11] the ACS and AHCPR , present guidelines for screen- detect the vast majority of adenomas . Because colo- ing average-risk patients in the form of lists of options rectal cancers bleed intermittently, 50% or more of (Table 1). The options include annual fecal occult blood patients with colorectal cancer may have a negative [11,12] test (not included as a stand alone test in the ACS test result . Thus, to be effective, FOBT must be guidelines), flexible sigmoidoscopy every 5 years, annual administered annually or biennially, which makes fecal occult blood test plus flexible sigmoidoscopy every patient compliance a problem. Furthermore, the positive 5 years, double-contrast barium enema every 5 to 10 predictive value of FOBT is only approximately [11,12] years, and colonoscopy every 10 years. 10% . Multidisciplinary Symposium — screening for cancer 11 Flexible sigmoidoscopy Barium enema examination Because of its higher sensitivity than single contrast Data from two case–control studies support the effec- barium enema, double-contrast barium enema is consid- tiveness of flexible sigmoidoscopy in reducing colorectal [13,14] ered the current radiologic alternative to colonoscopy cancer mortality . Individuals in these studies who for colorectal cancer detection. Similar to colonoscopy, had undergone at least one screening sigmoidoscopy barium enema examination is a test that allows evalu- during the previous 10 years had only a 21% to 30% risk ation of the entire colon in approximately 90–95% of of developing fatal colorectal cancer as control subjects. [29–31] patients . No data are available on the sensitivity of Compared with colonoscopy, flexible sigmoidoscopy double-contrast barium enema in a screening popula- is less expensive and has a lower complication rate tion. In patients undergoing diagnostic examinations, (approximately one to two perforations per 10 000 ex- [6,15] the reported sensitivity of this test for the detection of aminations) . In addition, it requires a less rigorous [32–34] cancer is 85–90% , and the sensitivity for adenomas bowel preparation and does not require sedation. The [35,36] larger than 1 cm is 75–90% . However, recently major disadvantage of flexible sigmoidoscopy, however, published data from the National Polyp Study in the is that it examines only a portion of the colon, thereby United States demonstrated a sensitivity for double- enabling detection of only approximately 50% of colonic [16,17] contrast barium enema of only approximately 50% for lesions . If a polyp is detected by sigmoidoscopy, polyps 1 cm or larger in patients undergoing surveillance colonoscopy is still needed to evaluate the entire colon. [37] after removal of adenomatous polyps . Advantages of double-contrast barium enema compared with colon- oscopy are that it is safer (approximately one perfora- Fecal occult blood testing combined with [38] tion in 25 000 procedures) , less expensive, and does flexible sigmoidoscopy not require sedation. Its major disadvantages are its The rationale for combining FOBT with flexible sig- lower sensitivity and the inability to remove polyps, thus moidoscopy is two-fold: (1) approximately half of the requiring colonoscopy or sigmoidoscopy after positive cancers missed by FOBT would be detected at sig- examinations. moidoscopy, and (2) FOBT is insensitive for detecting adenomas, many of which would be detected at sig- moidoscopy. Nevertheless, there is little direct evidence Computed tomography (CT) colonography to support such a combined approach. Furthermore, a CT colonography (also known as ‘virtual colonoscopy’) large number of colonic adenomas and carcinomas are is a relatively new radiologic procedure that holds not within reach of the sigmoidoscope. Although some promise as a colorectal cancer-screening test, but of these lesions would be detected when a positive requires further evaluation. In this study a helically sigmoidoscopy leads to a follow-up colonoscopy or acquired volumetric data set of the abdomen and pelvis barium enema, many of them would be missed, as up to is obtained after insufflation of the colon with air or 50% of proximal colonic cancers are not associated with [18–22] carbon dioxide. The colon can then be viewed with a distal adenoma . either 2-dimensional or 3-dimensional techniques. The 3-dimensional visualization technique provides a per- spective that simulates colonoscopic navigation of the Colonoscopy colonic lumen. Prospective studies performed in selected Colonoscopy is the only colorectal cancer screening test groups of high-risk patients have reported sensitivities that allows evaluation of the entire colon and provides with CT colonography of 50% to 91% for polyps 1 cm or the opportunity to remove polyps and small polypoid [39–43] larger . It is important to note, however, that the cancers at the same time. Although there are no con- results of such studies cannot be generalized to a screen- trolled trials demonstrating that screening colonoscopy ing population of average-risk individuals. One potential reduces colorectal cancer incidence or mortality in advantage of CT colonography is the possibility of those at average risk for the disease, indirect evidence avoiding rigorous bowel preparation through the use of for the effectiveness of colonoscopy comes from one barium stool tagging and electronic subtraction of stool [15] case–control study and uncontrolled observational from the colon prior to diagnostic evaluation of the [23–25] studies . The case–control study showed a 40% to [44] images . Whether CT colonography will become a 50% reduction in colorectal cancer incidence in individ- viable alternative to colonoscopy for colorectal cancer uals who had undergone colonoscopy or polypec- screening remains to be seen. [15] tomy . A limitation of colonoscopy is that it is [18,19,26] incomplete in 5–15% of patients . In addition, colonoscopy is associated with the highest risk of com- Cost-effectiveness plications of all screening tests. Perforation occurs in approximately 1 in 1000 colonoscopies, major bleeding Most studies of the cost-effectiveness of FOBT (every 1 occurs in approximately 3 per 1000, and one to three to 2 years), flexible sigmoidoscopy (every 5 years), patients undergoing colonoscopy die of complications colonoscopy (every 10 years) and double-contrast [6,19,26–28] from the procedure . barium enema examination (every 5 to 10 years) have 12 Multidisciplinary Symposium — screening for cancer Table 2 Recommendations for colorectal cancer screening in individuals at increased risk* First-degree relative with colorectal cancer or adenomatous polyp(s): same as for average risk individual, but begin at age 40 Family history of FAP Genetic counseling (consider genetic testing) Annual flexible sigmoidoscopy beginning at puberty if gene carrier or indeterminate Family history of HNPCC Genetic counseling (consider genetic testing) Colonoscopy every 1–2 years beginning at age 20–30, annually beginning at age 40 History of inflammatory bowel disease Consider colonoscopy surveillance for dysplasia every 1–2 years beginning after 8 years of disease for pancolitis and after 15 years of disease for left-sided colitis *Winawer SJ, Fletcher RH, Miller L et al. Colorectal cancer screening: clinical guidelines and rationale. Gastroenterology 1997; 112: 594–642. FAP, familial adenomatous polyposis; HNPCC, hereditary nonpolyposis colorectal cancer. shown costs per life-year saved ranging from approxi- colitis are also at increased risk for colorectal cancer, but mately $2000 to $15 000 for FOBT up to $22 000 for the risk is lower than that associated with ulcerative [45–48] [55] colonoscopy . These figures compare favorably with colitis . Familial adenomatous polyposis coli (FAP) is estimates of cost per life-year saved for breast cancer, a disease that results from inherited or acquired defects cervical cancer and hypertension screening programs, in the APC gene located on the fifth chromosome. [49–50] which range from approximately $9000 to $50 000 . Patients with this disease develop numerous polyps throughout the colon, which results in a 100% risk of colorectal cancer if the colon is not removed. Hereditary nonpolyposis colorectal cancer (HNPCC) is an auto- Screening recommendations (Table 1) somal dominant disorder that results in a familial pre- Recommended options for colorectal cancer screening disposition to multiple cancers. The colon cancers of asymptomatic individuals of average risk include the typically occur at a young age, are often located in the following (beginning at age 50): annual FOBT (if right colon, and may be associated with extracolonic [56] positive, examine entire colon with colonoscopy or neoplasms . double-contrast barium enema examination), flexible sigmoidoscopy every 5 years (followed by colonoscopy if adenomatous polyp or cancer found), annual FOBT and Screening recommendations (Table 2) sigmoidoscopy every 5 years, colonoscopy every 10 For individuals with first-degree relatives with colo- years, or double-contrast barium enema examination rectal cancer or an adenomatous polyp, the screening every 5–10 years. It should be noted that the American recommendations are the same as for the average risk Cancer Society does not endorse the option of FOBT by population, except that screening should begin at age 40. itself because of the relatively low mortality reductions [5] (Patients with a personal history of colorectal cancer or that have been associated with its use . adenomatous polyp are not included in this discussion, as they fall under the category of surveillance rather than screening.) The recommendation for patients with High-risk population FAP is to receive genetic counseling (and possibly Individuals at increased risk for colorectal cancer are genetic testing to determine if the patient is a gene those with: (1) a personal or family (first degree relative) carrier) and to undergo flexible sigmoidoscopy annually history of colorectal cancer or adenoma; (2) longstand- beginning at puberty. The recommendation for patients ing ulcerative or Crohn’s colitis; or (3) a genetic predis- with HNPCC is to receive genetic counseling (and position to a hereditary polyposis or nonpolyposis possibly genetic testing) and to undergo colonoscopy syndrome. Individuals with a single first-degree relative every 1–2 years beginning at age 20–30, with annual with colorectal cancer have a risk of developing colo- colonoscopies beginning at age 40. The recommendation rectal cancer approximately 1.7 times that of the general for patients with longstanding ulcerative colitis is to [51] population . In addition, cancers tend to occur at an undergo colonoscopy with biopsies looking for dysplasia earlier age in this population. First-degree relatives of every 1–2 years beginning 8 years after diagnosis for patients with adenomas have a similar increased risk pancolitis and beginning 15 years after diagnosis for [52,53] of colorectal cancer . Patients with long-standing left-sided disease. 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Risk of colorectal N Am 1999; 83: 1403–22. cancer in the families of patients with adenomatous polyps. The digital object identifier for this article is: 10.1102/ National Polyp Study Workgroup. N Engl J Med 1996; 334: 82–7. 1470-7330.2001.008 Ovarian cancer screening B Rufford, U Menon and I Jacobs Gynaecology Cancer Research Unit, St Bartholomew’s and the Royal London Medical and Dental School, London, UK Introduction What to screen for A screening programme should ideally be based on the Ovarian cancer is the most common gynaecological detection of a pre-malignant condition in order to lower malignancy in the developed world. It also carries the disease incidence and maximize mortality reduction, as worst prognosis with an overall 5-year survival of 30%. is the case with the cervical screening programme. This is likely to be due to the disease frequently present- Although it is suggested that inclusion cysts and benign ing late, the ovary position within the peritoneal cavity and borderline ovarian tumours may be pre-malignant, resulting in minimal local irritation, or interference with this remains speculative. Crayford et al. recently ana- vital structures until ovarian enlargement is consider- lysed follow-up data from an ovarian cancer screening able, or metastasis occurs. Seventy per cent of women trial to assess whether removal of persistent ovarian are diagnosed with stage III or IV disease, with 5-year cysts was associated with a reduction in mortality from [1] survivals of 15–20% and less than 5%, respectively . [3] ovarian cancer . No such reduction was found relative Despite an increase in understanding of the molecular to other cancers, although it is difficult to interpret the events underlying malignancy, and advances in both findings in the absence of a control group, and incidence surgery and chemotherapy, the overall prognosis of may have been a more appropriate end-point than ovarian cancer has changed little over the last 30 years. mortality. In the absence of confirmed pre-malignant However, women who are diagnosed at an early stage do change, screening for ovarian cancer is directed at have a significantly improved prognosis, with survival of present to the detection of pre-clinical disease. above 80% in stage I disease, and above 90% in those [2] diagnosed at stage Ia . The best way of improving outcome may be, therefore, to detect the condition at an What is required from a screening test early stage, when the prognosis remains relatively good, via a screening programme. This is an exciting prospect A suitable screening test requires both high sensitivity and screening trials have shown some encouraging and specificity. Women who have a positive screen results. However, as yet screening has not been shown require further investigation, often in the form of ex- conclusively to reduce mortality from ovarian cancer. In ploratory surgery. It is therefore imperative to maximize addition, our lack of knowledge about disease progres- specificity in order to obtain a high positive predictive sion and of primary peritoneal cancer, as well as the value, and decrease the number of false-positive screens. possible surgical and psychological morbidity that may In the general population, a specificity of 99.6% is result from screening, should be considered. There are required to achieve a positive predictive value of [4] also, of course, cost implications. 10% , i.e. to limit the number of unnecessary surgical

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