Dig Dis Sci (2015) 60:634–638 DOI 10.1007/s10620-015-3610-3
REVIEW
Flexible Sigmoidoscopy: More Than a Unilateral Breast Exam? Robert S. Bresalier
Published online: 5 March 2015 Ó Springer Science+Business Media New York 2015
Upon reviewing the many wonderful articles and perspective pieces in this Special Issue of Digestive Diseases and Sciences prior to publication, it occurred to me that an important method of screening had not been covered. While in 2010 in the USA \6 % of respondents aged 50–75 reported having screening flexible sigmoidoscopy performed within 5 years (an additional 1.3 % had sigmoidoscopy plus fecal occult blood testing) [1, 2], flexible sigmoidoscopy remains part of the menu of screening options recommended by several professional society guidelines [3–6]. Four recent randomized trials also provide (arguably) the largest body of prospective evidence demonstrating the role of colorectal cancer (CRC) screening in reducing CRC-related mortality of any screening method [7–10]. I therefore decided that it was important to at least provide a brief perspective on flexible sigmoidoscopy as a CRC screening tool, including why it is not used more today in the USA. Four large prospective randomized trials of flexible sigmoidoscopy for CRC screening were published in highimpact journals between 2004 and 2014, having been initiated in the 1990s when flexible sigmoidoscopy was a more common screening tool than in the USA today (Table 1) [7–10]. The trials from the UK (the UK Flexible Sigmoidoscopy Trial), Italy (the Italian Randomized Controlled Trial-SCORE), the USA (the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial-PLCO), and Norway (the Norwegian Colorectal Cancer Prevention Trial-NORCAPP) differ in several ways including how
R. S. Bresalier (&) Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1466, Houston, TX 77030, USA e-mail: [email protected]
123
participants were recruited, the number of screening examinations performed, degree of screening outside the trial (‘‘contamination’’), and what findings at sigmoidoscopy generated a subsequent colonoscopy. All, however, demonstrated similar relative and absolute reductions in CRC incidence and cancer-related incidence and mortality. The UK Flexible Sigmoidoscopy Screening Trial is a randomized trial which tested the hypothesis that a single flexible sigmoidoscopy screening examination offered at approximately 60 years of age can lower the incidence and mortality of CRC [7]. CRC incidence and mortality were reduced by 23 and 31 %, respectively, in the intention-totreat analysis (33 and 43 %, respectively, based on perprotocol analysis); incidence of cancer of the rectum and sigmoid was reduced by 36 % in the intention-to-treat analysis and 50 % in the per-protocol analysis. These data have resulted in once in a lifetime flexible sigmoidoscopy being included as an option in the UK National Health Service Bowel Cancer Screening Programme (FOBT is the other option). The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) enrolled 154,900 subjects of age 55–74 years in a prospective randomized trial that compared flexible sigmoidoscopy with repeat screening at 3 or 5 years to a usual-care control group [8]. Flexible sigmoidoscopy reduced CRC incidence by 21 % with a benefit observed in both the proximal and distal colon and reduced overall mortality by 26 % (intention-to-treat analyses). Mortality from distal CRC (distal to the splenic flexure) was reduced by 50 %, whereas mortality from proximal CRC was unaffected. The Italian Randomized Controlled Trial (SCORE) demonstrated that once-only sigmoidoscopy significantly reduced CRC incidence by 18 % and insignificantly reduced mortality by 22 % in intention-to-treat analyses; in
Once-only FS with removal of polyps B10 mm; colonoscopy in subjects with high-risk findings 11.2 years 57,237 113,195 40,621 23 % reduction (95 % CI 0.70–0.84) 31 % reduction (95 % CI 0.59–0.82)
Screening strategy
Follow-up duration (median years)
No. screening arm
No. control arm
No. actually screened
Effect on CRC incidence (ITT)
Effect on mortality (ITT) overall
28 % reduction (95 % CI 0.48–1.09)
22 % reduction (95 % CI 0.56–1.08)
18 % reduction (95 % CI 0.69–0.96)
9,911
17,144
17,148
11.4 years for mortality
10.5 years for incidence
Once-only FS with removal of polyps B5 mm; colonoscopy in subjects with high-risk findings
SCORE (Italy) (9)
ITT intention to treat, N number of subjects, FS flexible sigmoidoscopy, FOBT fecal occult blood testing
Effect on mortality (ITT) distal CRC
UK flexible sigmoidoscopy trial (7)
Study
Table 1 Randomized controlled trials of flexible sigmoidoscopy
50 % reduction (95 % CI 0.38–0.64)
26 % reduction (95 % CI 0.63–0.87)
21 % reduction (95 % CI 0.72–0.85)
41,820 (3 or 5 years)
64,667 (baseline)
77,445
77,445
11.9 years
FS at baseline and at 3 or 5 years; subjects with positive findings referred to primary physician for follow-up
PLCO (USA) (8)
21 % reduction (95 % CI 0.55–1.11)
27 % reduction (95 % CI 0.56–0.94)
20 % reduction (95 % CI 0.70–0.92)
12,960
78,220
20,572
10.9 years
Once-only FS or once-only FS ?FOBT; colonoscopy in subjects with any adenoma, or polyp C10 mm
NORCAPP (Norway) (10)
Dig Dis Sci (2015) 60:634–638 635
123
636
per-protocol analyses, incidence and mortality were reduced 31 and 38 %, respectively, both significant [9]. The Norwegian Colorectal Cancer Prevention Trial (NORCAPP) is a population-based trial which randomized 100,210 individuals aged 50–64 years to receive once-only flexible sigmoidoscopy or the combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening tests were offered colonoscopy. The control group received no intervention. Colorectal cancer incidence and mortality were reduced 20 and 27 %, respectively, in the sigmoidoscopy group compared to the no-screening control group during a median follow-up of 11 years. There was no difference between the flexible sigmoidoscopy only versus the flexible sigmoidoscopy and FOBT screening groups. Given these remarkable results from US and European prospective trials, why is flexible sigmoidoscopy an uncommonly used CRC screening test in the USA? The decline in flexible sigmoidoscopy as a method of CRC screening in the USA has its roots in at least three historic events and observations. The first occurred in 2000 when a former president of the American Gastroenterological Association famously likened performing flexible sigmoidoscopy for CRC screening to ‘‘performing mammography of one breast to screen women for breast cancer’’ [11]. These sentiments were put forth in a New England of Journal of Medicine editorial based on two landmark papers indicating that approximately 50 % of patients with advanced proximal colorectal lesions (cancers and advanced adenomas proximal to the splenic flexure) had no distal adenomas on colonoscopy [12, 13]. The presumption was that had these individuals only had screening with flexible sigmoidoscopy, these important proximal lesions would have been missed. The prevalence of advanced proximal neoplasia among patients with no distal polyps (beyond the splenic flexure) was 1.5 and 2.7 % in the two studies. In each of these studies, findings distal to the splenic flexure at colonoscopy served as a surrogate for what might have been found at flexible sigmoidoscopy. One of the studies performed in a Veterans Affairs medical center with a predominantly male population also included a disproportionately large number of patients who were at increased risk of CRC because of a positive family history [13]. The second event likely to have had a major impact on the decline in the use of flexible sigmoidoscopy for CRC screening in the USA came on July 1, 2001 when Medicare and subsequently many private insurers began paying for screening colonoscopy. The American College of Gastroenterology, while continuing to advocate a ‘‘menu’’ of options for CRC screening, subsequently recommended colonoscopy as the ‘‘preferred’’ screening option [5]. Modifications of health care payments allowing enhanced
123
Dig Dis Sci (2015) 60:634–638
access under the Affordable Care Act will likely increase the disproportionate use of colonoscopy in the USA [14]. Recently reported data indicate that over a 20-year period (SEER data; 1991–2011), the US colorectal cancer incidence (all races, males, females) has fallen from 59.5 cases to 39.3 cases per 100,000 (a 35 % reduction) with a corresponding mortality reduction over the same time period from 24.0 to 15.1 deaths per 100,000 (37 % reduction) [15]. While a variety of screening options were available during this period, many have pointed to the increased use of colonoscopy as a responsible component of this decline in CRC-related mortality. The third event which hastened the demise of screening flexible sigmoidoscopy in the USA was increased recognition of existence of the ‘‘flat’’ polyp and sessile serrated polyps. While ‘‘flat’’ polyps (endoscopically defined as those with a height of less than half of the lesion diameter) have been recognized for many years, especially in the Japanese literature [16], a report from a Veterans Affairs Hospital group that non-polypoid colorectal neoplasms are relatively common lesions that have a greater association with carcinoma compared with polypoid neoplasms regardless of size, led to increased use of colonoscopy and techniques such as chromoendoscopy, since many of these lesions are subtle and occur in the proximal colon [17]. Public demand for enhanced endoscopic techniques so that flat lesions would not be missed (and a brief panic over the results) was stimulated, in part, by a report of these findings in the New York Times [18]. Sessile serrated adenomas (SSAs) are distinct from conventional adenomas with respect to histology and molecular biology [19]. They are characterized by distorted crypt bases and crypt dilation and by migration of the proliferative zone to the upper zones of the crypt. SSAs are associated with BRAF mutations and CIMP, which can lead to epigenetic silencing of mismatch repair genes such as MLH1, resulting in microsatellite instability. SSAs are typically right-sided, often flat, and may be covered by a so-called mucous cap. The suggestion that these lesions may have an accelerated natural history toward carcinoma, accounting for at least some interval cancers, and their frequent occurrence in the proximal colon, has also led to a preference for colonoscopy as the preferred screening tool in the USA. Colonoscopy may well be the most effective tool for CRC screening, but data from prospective randomized trials are at present lacking to support this conclusion; a large prospective Veterans Administration screening trial is underway in the USA, and several other trials ongoing in Europe are designed to test this hypothesis. The National Polyp Study, reporting on the impact of polypectomy and surveillance on CRC-related outcomes, strongly suggested a reduction in CRC mortality as the result of removing adenomatous polyps at colonoscopy compared with
Dig Dis Sci (2015) 60:634–638
historic reference populations. A recent update of this trial with median follow-up of 15.8 years indicated that colonoscopic polypectomy is associated with a 53 % reduction in mortality from CRC compared with the expected incidence-based mortality from CRC in the general population [20]. A Canadian population-based study compared the risk of developing CRC after a negative colonoscopy in all Ontario residents who had a history of a complete negative colonoscopy with controls that consisted of the Ontario population without a history of colonoscopy [21]. In the negative colonoscopy cohort, the relative risk of distal CRC was significantly lower than that of the control group in each of the 14 years of follow-up, and the relative risk of proximal CRC was significantly lower mainly during the last 7 years of follow-up. A second Canadian case–control study demonstrated that complete colonoscopy also was associated with fewer deaths from left-sided CRC but not from right-sided cancer [22]. Several other population-based analyses and analyses of individual screening programs in the USA, Canada, and Europe also suggest that increased use of colonoscopy is associated with mortality reduction from CRC, but that this reduction varies by site of the cancer [23–27]. A large case–control study using SEER-Medcare data demonstrated that colonoscopy was associated with a 60 % decreased risk of CRC-related death, but the association was stronger for distal (OR 0.24; 95 % CI 0.21–0.27) than proximal (OR 0.58; 95 % CI 0.53–0.64) CRC, consistent with European and Canadian studies [26]. These findings are of interest in light of arguments for the superiority of colonoscopy to flexible sigmoidoscopy for CRC screening. While it would be dangerous to compare results from these observational colonoscopy studies (many of which were performed prior to the current emphasis on quality measures such as improved pre-colonoscopy preparation of the proximal colon) to results from prospective randomized flexible sigmoidoscopy trials (initiated in the 1990s), the impact on mortality of the two modalities has not yet been proven to be different. I think it is fair to say, however, that at the moment the comparison of flexible sigmoidoscopy to a unilateral breast exam deserves reconsideration. Conflict of interest
None.
References 1. Joseph DA, King JB, Miller JW, Richardson LC, Centers for Disease Control and Prevention. Prevalence of colorectal cancer screening among adults—behavioral factor surveillance system, United States, 2010. Morb Mortal Wkly Rep. 2012;61:51–56.
637 2. Steele CB, Rim SH, Joseph DA, et al. Colorectal cancer incidence and screening—United States, 2008 and 2010. Morb Mortal Wkly Rep. 2013;62:53–60. 3. Levin B, Lieberman DA, McFarland B, et al. American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Gastroenterology. 2008;5:1570–1595. 4. U.S. Preventative Services Task Force Screening for Colorectal Cancer. U.S. Preventative Services Task Force recommendation statement. Ann Int Med. 2008;149:627–637. 5. Rex, DK, Johnson, DA., Anderson, JC, Schoenfeld, PS, Burke CA., Inadomi JM. American College of Gastroenterology guidelines for colorectal cancer screening 2008. Am J Gastroenterol. 2009;104:739–750. 6. Sung JJY, Chan FKL, Chiu HM, et al. An updated Asia Pacific consensus recommendations on colorectal cancer screening. Gut. 2015;64:121–132. 7. Atkin WS, Edwards R, Kraj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer. Lancet. 2010;37:1624–1633. 8. Schoen RE, Pinsky PF, Weissfeld JL, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366:2345–2357. 9. Segnan N, Amaroli P, Bonelli L, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial-SCORE. J Natl Cancer Inst. 2011;103:1310–1322. 10. Holme O, Loberg M, Kalager M, et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality. A randomized clinical trial. JAMA. 2014;312:606–615. 11. Podolsky DK. Going the distance—the case for true colorectalcancer screening. N Engl J Med. 2000;343:207–208. 12. Imperiale TF, Wagner DJ, Lin CY, et al. Risk of advanced proximal neoplasms in asymptomatic adults according to distal colorectal findings. N Engl J Med. 2000;343:169–174. 13. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. N Engl J Med. 2000;343:162–168. 14. Pollitz K, Lucia K, Keith K, et al. Coverage of Colonoscopies Under the Affordable Care Act’s Prevention Benefit. Available at www.kkk.org, www.cancer.org, and www.nnnrt.org. 15. Surveillance E. End Results Program. SEER Stat Fact Sheets: Colon and Rectum Cancer: Centers for Disease Control; 2014 [cited 2014]. Available from: http://seer.cancer.gov/statfacts/ html/colorect.html. 16. Kudo S. Early Colorectal Cancer. Tokyo: Igaku-Shoin; 1996. 17. Soetikno RM, Kaltenbach T, Rouse RV, et al. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasm in asymptomatic and symptomatic adults. JAMA. 2008;299:1027–1035. 18. Grady D. Easily Overlooked Lesions Tied to Colon Cancer. New York Times; 2008. 19. Crockett SD, Snover DC, Ahnen DJ, Baron JA. Sessile serrated adenomas: an evidence-based guide to management. Clin Gastroenterol Hepatol. 2015;13:11–26. 20. Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012;366:687–696. 21. Lakoff J, Paszat LF, Saskin R, Rabeneck L. Risk of developing proximal versus distal colorectal cancer after a negative colonoscopy: a population based study. Clin Gastroenterol Hepatol. 2008;6:1117–1121. 22. Baxter NN, Goldwasser MA, Paszat LF, et al. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150:1–8.
123
638 23. Rabeneck L, Paszat LF, Saskin R, Stukel TA. Association between colonoscopy rates and colorectal cancer mortality. Am J Gastroenterol. 2010;105:1627–1632. 24. Brenner H, Hoffmeister M, Volker A, et al. Protection from rightand left-sided colorectal neoplasms after colonoscopy: population-based study. JNCI. 2010;102:89–95. 25. Stock C, Knudsen AB, Lansdorp-Vogelaar L, et al. Colorectal cancer mortality prevented by use and attributable to colonoscopy. Gastrointest Endosc. 2011;73:435–443.
123
Dig Dis Sci (2015) 60:634–638 26. Singh H, Nugent Z, Demers AA, et al. The reduction in colorectal cancer mortality after colonoscopy varies by site of cancer. Gastroenterology. 2010;139:1128–1137. 27. Kahi CJ, Imperiale TF, Juliar BE, Rex DK. Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol. 2009;7:770–775.
REVIEW
Flexible Sigmoidoscopy: More Than a Unilateral Breast Exam? Robert S. Bresalier
Published online: 5 March 2015 Ó Springer Science+Business Media New York 2015
Upon reviewing the many wonderful articles and perspective pieces in this Special Issue of Digestive Diseases and Sciences prior to publication, it occurred to me that an important method of screening had not been covered. While in 2010 in the USA \6 % of respondents aged 50–75 reported having screening flexible sigmoidoscopy performed within 5 years (an additional 1.3 % had sigmoidoscopy plus fecal occult blood testing) [1, 2], flexible sigmoidoscopy remains part of the menu of screening options recommended by several professional society guidelines [3–6]. Four recent randomized trials also provide (arguably) the largest body of prospective evidence demonstrating the role of colorectal cancer (CRC) screening in reducing CRC-related mortality of any screening method [7–10]. I therefore decided that it was important to at least provide a brief perspective on flexible sigmoidoscopy as a CRC screening tool, including why it is not used more today in the USA. Four large prospective randomized trials of flexible sigmoidoscopy for CRC screening were published in highimpact journals between 2004 and 2014, having been initiated in the 1990s when flexible sigmoidoscopy was a more common screening tool than in the USA today (Table 1) [7–10]. The trials from the UK (the UK Flexible Sigmoidoscopy Trial), Italy (the Italian Randomized Controlled Trial-SCORE), the USA (the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial-PLCO), and Norway (the Norwegian Colorectal Cancer Prevention Trial-NORCAPP) differ in several ways including how
R. S. Bresalier (&) Department of Gastroenterology, Hepatology and Nutrition, The University of Texas MD Anderson Cancer Center, 1515 Holcombe Boulevard, Unit 1466, Houston, TX 77030, USA e-mail: [email protected]
123
participants were recruited, the number of screening examinations performed, degree of screening outside the trial (‘‘contamination’’), and what findings at sigmoidoscopy generated a subsequent colonoscopy. All, however, demonstrated similar relative and absolute reductions in CRC incidence and cancer-related incidence and mortality. The UK Flexible Sigmoidoscopy Screening Trial is a randomized trial which tested the hypothesis that a single flexible sigmoidoscopy screening examination offered at approximately 60 years of age can lower the incidence and mortality of CRC [7]. CRC incidence and mortality were reduced by 23 and 31 %, respectively, in the intention-totreat analysis (33 and 43 %, respectively, based on perprotocol analysis); incidence of cancer of the rectum and sigmoid was reduced by 36 % in the intention-to-treat analysis and 50 % in the per-protocol analysis. These data have resulted in once in a lifetime flexible sigmoidoscopy being included as an option in the UK National Health Service Bowel Cancer Screening Programme (FOBT is the other option). The Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO) enrolled 154,900 subjects of age 55–74 years in a prospective randomized trial that compared flexible sigmoidoscopy with repeat screening at 3 or 5 years to a usual-care control group [8]. Flexible sigmoidoscopy reduced CRC incidence by 21 % with a benefit observed in both the proximal and distal colon and reduced overall mortality by 26 % (intention-to-treat analyses). Mortality from distal CRC (distal to the splenic flexure) was reduced by 50 %, whereas mortality from proximal CRC was unaffected. The Italian Randomized Controlled Trial (SCORE) demonstrated that once-only sigmoidoscopy significantly reduced CRC incidence by 18 % and insignificantly reduced mortality by 22 % in intention-to-treat analyses; in
Once-only FS with removal of polyps B10 mm; colonoscopy in subjects with high-risk findings 11.2 years 57,237 113,195 40,621 23 % reduction (95 % CI 0.70–0.84) 31 % reduction (95 % CI 0.59–0.82)
Screening strategy
Follow-up duration (median years)
No. screening arm
No. control arm
No. actually screened
Effect on CRC incidence (ITT)
Effect on mortality (ITT) overall
28 % reduction (95 % CI 0.48–1.09)
22 % reduction (95 % CI 0.56–1.08)
18 % reduction (95 % CI 0.69–0.96)
9,911
17,144
17,148
11.4 years for mortality
10.5 years for incidence
Once-only FS with removal of polyps B5 mm; colonoscopy in subjects with high-risk findings
SCORE (Italy) (9)
ITT intention to treat, N number of subjects, FS flexible sigmoidoscopy, FOBT fecal occult blood testing
Effect on mortality (ITT) distal CRC
UK flexible sigmoidoscopy trial (7)
Study
Table 1 Randomized controlled trials of flexible sigmoidoscopy
50 % reduction (95 % CI 0.38–0.64)
26 % reduction (95 % CI 0.63–0.87)
21 % reduction (95 % CI 0.72–0.85)
41,820 (3 or 5 years)
64,667 (baseline)
77,445
77,445
11.9 years
FS at baseline and at 3 or 5 years; subjects with positive findings referred to primary physician for follow-up
PLCO (USA) (8)
21 % reduction (95 % CI 0.55–1.11)
27 % reduction (95 % CI 0.56–0.94)
20 % reduction (95 % CI 0.70–0.92)
12,960
78,220
20,572
10.9 years
Once-only FS or once-only FS ?FOBT; colonoscopy in subjects with any adenoma, or polyp C10 mm
NORCAPP (Norway) (10)
Dig Dis Sci (2015) 60:634–638 635
123
636
per-protocol analyses, incidence and mortality were reduced 31 and 38 %, respectively, both significant [9]. The Norwegian Colorectal Cancer Prevention Trial (NORCAPP) is a population-based trial which randomized 100,210 individuals aged 50–64 years to receive once-only flexible sigmoidoscopy or the combination of once-only flexible sigmoidoscopy and fecal occult blood testing (FOBT). Participants with positive screening tests were offered colonoscopy. The control group received no intervention. Colorectal cancer incidence and mortality were reduced 20 and 27 %, respectively, in the sigmoidoscopy group compared to the no-screening control group during a median follow-up of 11 years. There was no difference between the flexible sigmoidoscopy only versus the flexible sigmoidoscopy and FOBT screening groups. Given these remarkable results from US and European prospective trials, why is flexible sigmoidoscopy an uncommonly used CRC screening test in the USA? The decline in flexible sigmoidoscopy as a method of CRC screening in the USA has its roots in at least three historic events and observations. The first occurred in 2000 when a former president of the American Gastroenterological Association famously likened performing flexible sigmoidoscopy for CRC screening to ‘‘performing mammography of one breast to screen women for breast cancer’’ [11]. These sentiments were put forth in a New England of Journal of Medicine editorial based on two landmark papers indicating that approximately 50 % of patients with advanced proximal colorectal lesions (cancers and advanced adenomas proximal to the splenic flexure) had no distal adenomas on colonoscopy [12, 13]. The presumption was that had these individuals only had screening with flexible sigmoidoscopy, these important proximal lesions would have been missed. The prevalence of advanced proximal neoplasia among patients with no distal polyps (beyond the splenic flexure) was 1.5 and 2.7 % in the two studies. In each of these studies, findings distal to the splenic flexure at colonoscopy served as a surrogate for what might have been found at flexible sigmoidoscopy. One of the studies performed in a Veterans Affairs medical center with a predominantly male population also included a disproportionately large number of patients who were at increased risk of CRC because of a positive family history [13]. The second event likely to have had a major impact on the decline in the use of flexible sigmoidoscopy for CRC screening in the USA came on July 1, 2001 when Medicare and subsequently many private insurers began paying for screening colonoscopy. The American College of Gastroenterology, while continuing to advocate a ‘‘menu’’ of options for CRC screening, subsequently recommended colonoscopy as the ‘‘preferred’’ screening option [5]. Modifications of health care payments allowing enhanced
123
Dig Dis Sci (2015) 60:634–638
access under the Affordable Care Act will likely increase the disproportionate use of colonoscopy in the USA [14]. Recently reported data indicate that over a 20-year period (SEER data; 1991–2011), the US colorectal cancer incidence (all races, males, females) has fallen from 59.5 cases to 39.3 cases per 100,000 (a 35 % reduction) with a corresponding mortality reduction over the same time period from 24.0 to 15.1 deaths per 100,000 (37 % reduction) [15]. While a variety of screening options were available during this period, many have pointed to the increased use of colonoscopy as a responsible component of this decline in CRC-related mortality. The third event which hastened the demise of screening flexible sigmoidoscopy in the USA was increased recognition of existence of the ‘‘flat’’ polyp and sessile serrated polyps. While ‘‘flat’’ polyps (endoscopically defined as those with a height of less than half of the lesion diameter) have been recognized for many years, especially in the Japanese literature [16], a report from a Veterans Affairs Hospital group that non-polypoid colorectal neoplasms are relatively common lesions that have a greater association with carcinoma compared with polypoid neoplasms regardless of size, led to increased use of colonoscopy and techniques such as chromoendoscopy, since many of these lesions are subtle and occur in the proximal colon [17]. Public demand for enhanced endoscopic techniques so that flat lesions would not be missed (and a brief panic over the results) was stimulated, in part, by a report of these findings in the New York Times [18]. Sessile serrated adenomas (SSAs) are distinct from conventional adenomas with respect to histology and molecular biology [19]. They are characterized by distorted crypt bases and crypt dilation and by migration of the proliferative zone to the upper zones of the crypt. SSAs are associated with BRAF mutations and CIMP, which can lead to epigenetic silencing of mismatch repair genes such as MLH1, resulting in microsatellite instability. SSAs are typically right-sided, often flat, and may be covered by a so-called mucous cap. The suggestion that these lesions may have an accelerated natural history toward carcinoma, accounting for at least some interval cancers, and their frequent occurrence in the proximal colon, has also led to a preference for colonoscopy as the preferred screening tool in the USA. Colonoscopy may well be the most effective tool for CRC screening, but data from prospective randomized trials are at present lacking to support this conclusion; a large prospective Veterans Administration screening trial is underway in the USA, and several other trials ongoing in Europe are designed to test this hypothesis. The National Polyp Study, reporting on the impact of polypectomy and surveillance on CRC-related outcomes, strongly suggested a reduction in CRC mortality as the result of removing adenomatous polyps at colonoscopy compared with
Dig Dis Sci (2015) 60:634–638
historic reference populations. A recent update of this trial with median follow-up of 15.8 years indicated that colonoscopic polypectomy is associated with a 53 % reduction in mortality from CRC compared with the expected incidence-based mortality from CRC in the general population [20]. A Canadian population-based study compared the risk of developing CRC after a negative colonoscopy in all Ontario residents who had a history of a complete negative colonoscopy with controls that consisted of the Ontario population without a history of colonoscopy [21]. In the negative colonoscopy cohort, the relative risk of distal CRC was significantly lower than that of the control group in each of the 14 years of follow-up, and the relative risk of proximal CRC was significantly lower mainly during the last 7 years of follow-up. A second Canadian case–control study demonstrated that complete colonoscopy also was associated with fewer deaths from left-sided CRC but not from right-sided cancer [22]. Several other population-based analyses and analyses of individual screening programs in the USA, Canada, and Europe also suggest that increased use of colonoscopy is associated with mortality reduction from CRC, but that this reduction varies by site of the cancer [23–27]. A large case–control study using SEER-Medcare data demonstrated that colonoscopy was associated with a 60 % decreased risk of CRC-related death, but the association was stronger for distal (OR 0.24; 95 % CI 0.21–0.27) than proximal (OR 0.58; 95 % CI 0.53–0.64) CRC, consistent with European and Canadian studies [26]. These findings are of interest in light of arguments for the superiority of colonoscopy to flexible sigmoidoscopy for CRC screening. While it would be dangerous to compare results from these observational colonoscopy studies (many of which were performed prior to the current emphasis on quality measures such as improved pre-colonoscopy preparation of the proximal colon) to results from prospective randomized flexible sigmoidoscopy trials (initiated in the 1990s), the impact on mortality of the two modalities has not yet been proven to be different. I think it is fair to say, however, that at the moment the comparison of flexible sigmoidoscopy to a unilateral breast exam deserves reconsideration. Conflict of interest
None.
References 1. Joseph DA, King JB, Miller JW, Richardson LC, Centers for Disease Control and Prevention. Prevalence of colorectal cancer screening among adults—behavioral factor surveillance system, United States, 2010. Morb Mortal Wkly Rep. 2012;61:51–56.
637 2. Steele CB, Rim SH, Joseph DA, et al. Colorectal cancer incidence and screening—United States, 2008 and 2010. Morb Mortal Wkly Rep. 2013;62:53–60. 3. Levin B, Lieberman DA, McFarland B, et al. American Cancer Society Colorectal Cancer Advisory Group; US Multi-Society Task Force; American College of Radiology Colon Cancer Committee. Gastroenterology. 2008;5:1570–1595. 4. U.S. Preventative Services Task Force Screening for Colorectal Cancer. U.S. Preventative Services Task Force recommendation statement. Ann Int Med. 2008;149:627–637. 5. Rex, DK, Johnson, DA., Anderson, JC, Schoenfeld, PS, Burke CA., Inadomi JM. American College of Gastroenterology guidelines for colorectal cancer screening 2008. Am J Gastroenterol. 2009;104:739–750. 6. Sung JJY, Chan FKL, Chiu HM, et al. An updated Asia Pacific consensus recommendations on colorectal cancer screening. Gut. 2015;64:121–132. 7. Atkin WS, Edwards R, Kraj-Hans I, et al. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer. Lancet. 2010;37:1624–1633. 8. Schoen RE, Pinsky PF, Weissfeld JL, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med. 2012;366:2345–2357. 9. Segnan N, Amaroli P, Bonelli L, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial-SCORE. J Natl Cancer Inst. 2011;103:1310–1322. 10. Holme O, Loberg M, Kalager M, et al. Effect of flexible sigmoidoscopy screening on colorectal cancer incidence and mortality. A randomized clinical trial. JAMA. 2014;312:606–615. 11. Podolsky DK. Going the distance—the case for true colorectalcancer screening. N Engl J Med. 2000;343:207–208. 12. Imperiale TF, Wagner DJ, Lin CY, et al. Risk of advanced proximal neoplasms in asymptomatic adults according to distal colorectal findings. N Engl J Med. 2000;343:169–174. 13. Lieberman DA, Weiss DG, Bond JH, et al. Use of colonoscopy to screen asymptomatic adults for colorectal cancer. N Engl J Med. 2000;343:162–168. 14. Pollitz K, Lucia K, Keith K, et al. Coverage of Colonoscopies Under the Affordable Care Act’s Prevention Benefit. Available at www.kkk.org, www.cancer.org, and www.nnnrt.org. 15. Surveillance E. End Results Program. SEER Stat Fact Sheets: Colon and Rectum Cancer: Centers for Disease Control; 2014 [cited 2014]. Available from: http://seer.cancer.gov/statfacts/ html/colorect.html. 16. Kudo S. Early Colorectal Cancer. Tokyo: Igaku-Shoin; 1996. 17. Soetikno RM, Kaltenbach T, Rouse RV, et al. Prevalence of nonpolypoid (flat and depressed) colorectal neoplasm in asymptomatic and symptomatic adults. JAMA. 2008;299:1027–1035. 18. Grady D. Easily Overlooked Lesions Tied to Colon Cancer. New York Times; 2008. 19. Crockett SD, Snover DC, Ahnen DJ, Baron JA. Sessile serrated adenomas: an evidence-based guide to management. Clin Gastroenterol Hepatol. 2015;13:11–26. 20. Zauber AG, Winawer SJ, O’Brien MJ, et al. Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med. 2012;366:687–696. 21. Lakoff J, Paszat LF, Saskin R, Rabeneck L. Risk of developing proximal versus distal colorectal cancer after a negative colonoscopy: a population based study. Clin Gastroenterol Hepatol. 2008;6:1117–1121. 22. Baxter NN, Goldwasser MA, Paszat LF, et al. Association of colonoscopy and death from colorectal cancer. Ann Intern Med. 2009;150:1–8.
123
638 23. Rabeneck L, Paszat LF, Saskin R, Stukel TA. Association between colonoscopy rates and colorectal cancer mortality. Am J Gastroenterol. 2010;105:1627–1632. 24. Brenner H, Hoffmeister M, Volker A, et al. Protection from rightand left-sided colorectal neoplasms after colonoscopy: population-based study. JNCI. 2010;102:89–95. 25. Stock C, Knudsen AB, Lansdorp-Vogelaar L, et al. Colorectal cancer mortality prevented by use and attributable to colonoscopy. Gastrointest Endosc. 2011;73:435–443.
123
Dig Dis Sci (2015) 60:634–638 26. Singh H, Nugent Z, Demers AA, et al. The reduction in colorectal cancer mortality after colonoscopy varies by site of cancer. Gastroenterology. 2010;139:1128–1137. 27. Kahi CJ, Imperiale TF, Juliar BE, Rex DK. Effect of screening colonoscopy on colorectal cancer incidence and mortality. Clin Gastroenterol. 2009;7:770–775.
