The National Polyp Study at 40: challenges then and now
2020; Elsevier BV; Volume: 93; Issue: 3 Linguagem: Inglês
10.1016/j.gie.2020.09.044
ISSN1097-6779
AutoresSidney J. Winawer, Ann G. Zauber, Michael J. O’Brien, Joseph E. Geenen, Jerome D. Waye,
Tópico(s)Genetic factors in colorectal cancer
ResumoThis is a 40-year perspective of the National Polyp Study (NPS), a randomized clinical trial (RCT) sponsored by the American Society for Gastrointestinal Endoscopy, American Gastroenterology Association, and American College of Gastroenterology and funded by the National Cancer Institute with conceptualization and planning starting in 1977 and accrual beginning in 1980. We review how we approached challenges presented by the introduction of colonoscopy and polypectomy, how these findings influenced clinical practice and public health, and how the NPS model was used to address new challenges. Details of the NPS concepts, design, results, and discussion may be obtained from our previously published studies as cited in the references.1Winawer S.J. Zauber A.G. O'Brien M.J. et al.Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.N Engl J Med. 1993; 328: 901-906Crossref PubMed Scopus (837) Google Scholar, 2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar, 3Winawer S.J. Zauber A.G. Gerdes H. et al.Risk of colorectal cancer in the families of patients with adenomatous polyps. National Polyp Study Workgroup.N Engl J Med. 1996; 334: 82-87Crossref PubMed Scopus (282) Google Scholar, 4Winawer S.J. Stewart E.T. Zauber A.G. et al.A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. National Polyp Study Work Group.N Engl J Med. 2000; 342: 1766-1772Crossref PubMed Scopus (501) Google Scholar, 5Zauber A.G. Winawer S.J. O'Brien M.J. et al.Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.N Engl J Med. 2012; 366: 687-696Crossref PubMed Scopus (1720) Google Scholar, 6O'Brien M.J. Winawer S.J. Zauber A.G. et al.The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas.Gastroenterology. 1990; 98: 371-379Crossref PubMed Scopus (690) Google Scholar, 7Winawer S.J. Zauber A.G. O'Brien M.J. et al.The National Polyp Study. Design, methods, and characteristics of patients with newly diagnosed polyps. The National Polyp Study Workgroup.Cancer. 1992; 70: 1236-1245Crossref PubMed Scopus (131) Google Scholar, 8Winawer S.J. Zauber A.G. The advanced adenoma as the primary target of screening.Gastrointest Endosc Clin North Am. 2002; 12 (v): 1-9Abstract Full Text Full Text PDF PubMed Scopus (245) Google Scholar, 9O’Brien M.J. Winawer S.J. Zauber A.G. et al.Flat adenomas in the National Polyp Study: Is there increased risk for high-grade dysplasia initially or during surveillance?.Clin Gastroenterol Hepatol. 2004; 2: 905-911Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar The NPS was an RCT of the timing of surveillance intervals after colonoscopic polypectomy. It also addressed colorectal cancer (CRC) incidence and mortality reduction, familial risk for CRC, use of advanced adenomas as a CRC surrogate, and implications of flat and serrated lesions. Colonoscopy had been introduced in the early 1970s, and colonoscopic polypectomy was shown to be feasible in the mid-1970s. Common practice was yearly colonoscopy after the removal of adenomas. However, observations from Lockhart-Mummery and Dukes10Lockhart-Mummery H. Dukes C. The pre-cancerous changes in the rectum and colon.Surg Gynecol Obstet. 1928; 46: 591-596Google Scholar and Muto et al11Muto T. Bussey H.J. Morson B.C. The evolution of cancer of the colon and rectum.Cancer. 1975; 36: 2251-2270Crossref PubMed Scopus (1802) Google Scholar of the progressive pathology of adenomas and follow-up of a small number of patients suggested that small benign adenomas took a long time to progress into more-advanced pathology and cancer. An RCT was designed in which patients with newly diagnosed, resected, and pathology-proven adenomas were assigned to have their first surveillance colonoscopy deferred to 3 years versus having a colonoscopy at 1 and 3 years.1Winawer S.J. Zauber A.G. O'Brien M.J. et al.Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.N Engl J Med. 1993; 328: 901-906Crossref PubMed Scopus (837) Google Scholar,7Winawer S.J. Zauber A.G. O'Brien M.J. et al.The National Polyp Study. Design, methods, and characteristics of patients with newly diagnosed polyps. The National Polyp Study Workgroup.Cancer. 1992; 70: 1236-1245Crossref PubMed Scopus (131) Google Scholar It was difficult to enlist endoscopists in a trial in which the first postpolypectomy colonoscopy was deferred to 3 years, to convince the National Cancer Institute to fund it, and to enroll patients. The 3-year interval was chosen because a 2-year interval was not substantially longer than 1 year and more than 3 years was not acceptable to the participating endoscopy investigators. Their concern regarding missed significant pathology, especially cancer, was so high that they insisted on a fecal occult blood test each year. There had been no prior reports of a 3-year postpolypectomy surveillance interval. Before this, the NPS model of a postpolypectomy randomized trial had never before been conceptualized. Our analysis showed no difference in the accumulated percentage of patients with advanced adenomas in the 2 arms of the study (relative risk, 1.0; 95% confidence interval, –.5 to 2.2) (Fig. 1). Based on the evidence in this well-designed clinical trial, it was possible to convince clinicians to accept new guidelines recommending the deferral of the first surveillance colonoscopy to 3 years.1Winawer S.J. Zauber A.G. O'Brien M.J. et al.Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.N Engl J Med. 1993; 328: 901-906Crossref PubMed Scopus (837) Google Scholar,2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar,12Winawer S.J. Fletcher R.H. Miller L. et al.Colorectal cancer screening: clinical guidelines and rationale.Gastroenterology. 1997; 112: 594-642Abstract Full Text Full Text PDF PubMed Scopus (1727) Google Scholar The NPS observation of benefit and risk in deferring the first surveillance colonoscopy encouraged the concept of further lengthening this interval.1Winawer S.J. Zauber A.G. O'Brien M.J. et al.Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.N Engl J Med. 1993; 328: 901-906Crossref PubMed Scopus (837) Google Scholar,13Zauber A. Winawer S. Bond J. et al.Can surveillance intervals be lengthened following colonoscopic polypectomy?.Gastroenterology. 1997; 112: A50Google Scholar The European Polyp Surveillance Study (EPoS) is investigating this concept in a current RCT. The EPoS randomized patients with low-risk (ie, nonadvanced) adenomas and high-risk (ie, advanced) adenomas to shorter and longer intervals, respectively, for colonoscopy surveillance.14Jover R. Bretthauer M. Dekker E. et al.Rationale and design of the European Polyp Surveillance (EPoS) trials.Endoscopy. 2016; 48: 571-578Crossref PubMed Scopus (64) Google Scholar The scientific environment is now more favorable to supporting larger trials with a CRC outcome measure. It has taken many years for clinicians to become comfortable with the safety of initially deferring the first surveillance colonoscopy to 3 years and subsequently deferring low-risk patients to 5 years15Winawer S. Fletcher R. Rex D. et al.Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence.Gastroenterology. 2003; 124: 544-560Abstract Full Text PDF PubMed Scopus (1920) Google Scholar and then more recently to 5 to 10 years.16Winawer S.J. Zauber A.G. Fletcher R.H. et al.Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.Gastroenterology. 2006; 130: 1872-1885Abstract Full Text Full Text PDF PubMed Scopus (598) Google Scholar, 17Levin B. Lieberman D.A. McFarland B. et al.Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.CA Cancer J Clin. 2008; 58: 130-160Crossref PubMed Scopus (1313) Google Scholar, 18Lieberman D.A. Rex D.K. Winawer S.J. et al.Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2012; 143: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1289) Google Scholar, 19Rex D.K. Boland C.R. Dominitz J.A. et al.Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 153: 307-323Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar Further lengthening of intervals for surveillance colonoscopies will be accepted based on well-designed clinical studies. Recent guidelines20Gupta S. Lieberman D. Anderson J.C. et al.Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Am J Gastroenterol. 2020; 115: 415-434Crossref PubMed Scopus (18) Google Scholar have reviewed additional cohort and case-control studies, which have provided evidence for lengthening such surveillance. Lockhart-Mummery and Dukes10Lockhart-Mummery H. Dukes C. The pre-cancerous changes in the rectum and colon.Surg Gynecol Obstet. 1928; 46: 591-596Google Scholar and Muto et al11Muto T. Bussey H.J. Morson B.C. The evolution of cancer of the colon and rectum.Cancer. 1975; 36: 2251-2270Crossref PubMed Scopus (1802) Google Scholar observed that risk of CRC in adenomas correlated with their pathology. Atkin et al21Atkin W.S. Morson B.C. Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas.N Engl J Med. 1992; 326: 658-662Crossref PubMed Scopus (897) Google Scholar reported that subsequent colon cancer risk was a function of the initial rectosigmoid adenoma pathology. Based on their findings in this retrospective cohort study from a pathology registry, Atkin et al suggested that colonoscopy surveillance may not be warranted in patients with only a single small rectosigmoid tubular adenoma. Atkin et al further concluded that follow-up colonoscopic examinations may be more appropriate for patients with tubulovillous, villous, or large adenomas in the rectosigmoid, especially if multiple adenomas are present.21Atkin W.S. Morson B.C. Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas.N Engl J Med. 1992; 326: 658-662Crossref PubMed Scopus (897) Google Scholar The NPS prospectively demonstrated that patients with more-advanced adenoma pathology at baseline had a greater CRC incidence reduction after polypectomy than those with nonadvanced pathology.2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar The NPS also demonstrated that patients could be stratified to low and high risk for future advanced adenomas according to their baseline adenoma characteristics.1Winawer S.J. Zauber A.G. O'Brien M.J. et al.Randomized comparison of surveillance intervals after colonoscopic removal of newly diagnosed adenomatous polyps. The National Polyp Study Workgroup.N Engl J Med. 1993; 328: 901-906Crossref PubMed Scopus (837) Google Scholar,2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar These findings led to subsequent 2003 guideline15Winawer S. Fletcher R. Rex D. et al.Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence.Gastroenterology. 2003; 124: 544-560Abstract Full Text PDF PubMed Scopus (1920) Google Scholar recommendations of risk stratification, with low-risk patients having their first surveillance colonoscopy examination at 5 years and those with high-risk adenomas having surveillance colonoscopy at 3 years. The 5-year surveillance for low-risk patients was based on low rates of advanced adenoma for over subsequent surveillance colonoscopies at 1, 3, and 6 years in the NPS. Although our NPS results were based on 6 years of surveillance, the guidelines elected 5-year surveillance for low-risk patients and 3 years for high risk. Five years were used as a more conservative wait time between surveillance colonoscopies and an interval more readily adoptable by clinicians. This surveillance time was also built on an analysis showing the cumulative risk of advanced adenomas over multiple surveillances. The proportion with advanced adenomas was low in those with baseline lower risk adenomas.13Zauber A. Winawer S. Bond J. et al.Can surveillance intervals be lengthened following colonoscopic polypectomy?.Gastroenterology. 1997; 112: A50Google Scholar Repeated studies have validated the risk stratification and have further expanded low-risk surveillance intervals to 5 to 10 years.16Winawer S.J. Zauber A.G. Fletcher R.H. et al.Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.Gastroenterology. 2006; 130: 1872-1885Abstract Full Text Full Text PDF PubMed Scopus (598) Google Scholar, 17Levin B. Lieberman D.A. McFarland B. et al.Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.CA Cancer J Clin. 2008; 58: 130-160Crossref PubMed Scopus (1313) Google Scholar, 18Lieberman D.A. Rex D.K. Winawer S.J. et al.Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2012; 143: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1289) Google Scholar, 19Rex D.K. Boland C.R. Dominitz J.A. et al.Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 153: 307-323Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar In addition, there is now an emphasis on relating continued surveillance to the findings of the first surveillance interval.20Gupta S. Lieberman D. Anderson J.C. et al.Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Am J Gastroenterol. 2020; 115: 415-434Crossref PubMed Scopus (18) Google Scholar Implementation of these concepts would reduce the burden of surveillance colonoscopy and provide more efficient use of resources for screening and diagnosis.16Winawer S.J. Zauber A.G. Fletcher R.H. et al.Guidelines for colonoscopy surveillance after polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer and the American Cancer Society.Gastroenterology. 2006; 130: 1872-1885Abstract Full Text Full Text PDF PubMed Scopus (598) Google Scholar, 17Levin B. Lieberman D.A. McFarland B. et al.Screening and surveillance for the early detection of colorectal cancer and adenomatous polyps, 2008: a joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology.CA Cancer J Clin. 2008; 58: 130-160Crossref PubMed Scopus (1313) Google Scholar, 18Lieberman D.A. Rex D.K. Winawer S.J. et al.Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2012; 143: 844-857Abstract Full Text Full Text PDF PubMed Scopus (1289) Google Scholar, 19Rex D.K. Boland C.R. Dominitz J.A. et al.Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 153: 307-323Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar, 20Gupta S. Lieberman D. Anderson J.C. et al.Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Am J Gastroenterol. 2020; 115: 415-434Crossref PubMed Scopus (18) Google Scholar The relationship of CRC to pre-existing adenomas was first reported in 1928 from St Mark’s Hospital in London.10Lockhart-Mummery H. Dukes C. The pre-cancerous changes in the rectum and colon.Surg Gynecol Obstet. 1928; 46: 591-596Google Scholar Proof of the longstanding belief that CRC developed mainly from pre-existing adenomas would provide a strong basis for the clinical practice of identifying and removing adenomatous polyps. There was no feasible and ethical approach to test the adenoma–carcinoma hypothesis in an RCT in which patients with adenomas would be randomized into a group for observation only. The NPS combined patients from both arms of the surveillance study into a single postpolypectomy cohort and compared the incidence of CRC in this cohort from which all polyps had been removed with an age- and sex-matched cohort from the general population (Surveillance and End Results) and to 2 reference groups21Atkin W.S. Morson B.C. Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas.N Engl J Med. 1992; 326: 658-662Crossref PubMed Scopus (897) Google Scholar,22Stryker S.J. Wolff B.G. Culp C.E. et al.Natural history of untreated colonic polyps.Gastroenterology. 1987; 93: 1009-1013Crossref PubMed Scopus (744) Google Scholar from the precolonoscopy era with polyps that had not been removed. Compared with the reference groups, there was a reduction in CRC incidence of 76% to 90% after an average follow-up of 5.9 years (Fig. 2). This supported the longstanding belief in the concept of the adenoma as the precursor to CRC and the practice of finding and removing adenomas to prevent CRC.2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar Our original article2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar included a sensitivity analysis on incidence reduction by starting the time at risk beginning 2 years after enrollment in the study. This reduced the number of person-years at risk and subsequently provided a smaller reduction for the effect of the polypectomy. No CRCs were detected before 3 years. These sensitivity CRC reductions were 66% (P < .01) to 86% (P < .001) rather than 76% to 90%. The 95% confidence intervals pertaining to these sensitivity analyses were still statistically significant. However, the importance of the NPS observation is not the precise number but rather that removing adenomas prevents cancer, proof of a longstanding concept that was first suggested in the 1928 St Mark’s report.10Lockhart-Mummery H. Dukes C. The pre-cancerous changes in the rectum and colon.Surg Gynecol Obstet. 1928; 46: 591-596Google Scholar This proof provided the rationale for colonoscopic polypectomy, with colonoscopy possibly as a screening examination, and the change of screening goals to include prevention as well as early-stage CRC detection. We excluded patients from the RCT who had large (>3 cm) sessile polyps because the endoscopists were reluctant to possibly have those patients’ surveillance deferred for 3 years. Endoscopists were concerned about randomizing patients with these lesions to possibly a 3-year deferred follow-up. Even today, such patients with large sessile polyps are excluded from the 3- versus 5-year surveillance intervals and have a shorter follow-up. After the NPS observations that removing adenomas reduced the expected rate of CRC, several cohort studies suggested that screening colonoscopy was effective.19Rex D.K. Boland C.R. Dominitz J.A. et al.Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 153: 307-323Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar,23Winawer S.J. The history of colorectal cancer screening: a personal perspective.Dig Dis Sci. 2015; 60: 596-608Crossref PubMed Scopus (38) Google Scholar There are now 2 randomized trials of screening colonoscopy compared with control subjects in progress to test this effect.24Bretthauer M. Kaminski M.F. Løberg M. et al.Population-based colonoscopy screening for colorectal cancer: a randomized clinical trial.JAMA Intern Med. 2016; 176: 894-902Crossref PubMed Scopus (148) Google Scholar,25Aronsson M. Carlsson P. Levin L. et al.Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer.Br J Surg. 2017; 104: 1078-1086Crossref PubMed Scopus (22) Google Scholar The benefit of removing adenomas to prevent CRC can be challenged as overdiagnosis and overtreatment. Perhaps the cancers emerging from adenomas would never have surfaced clinically in the patients’ lifetimes or if they had surfaced would not have been lethal. To address this issue, the long-term effect on CRC mortality in the NPS postpolypectomy cohort was initiated. All polyps identified on initial and surveillance colonoscopy were removed regardless of size. In a follow-up of the NPS cohort with matching to the National Death Index, mortality from CRC in patients with adenomas removed was compared with the incidence-based mortality in the general population (Surveillance and End Results) and with patients who had nonadenomatous polyps removed. A 53% reduction in CRC mortality was seen over a median of 15.8 years in patients who had adenomas removed compared with that expected in the general population (Fig. 3).5Zauber A.G. Winawer S.J. O'Brien M.J. et al.Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.N Engl J Med. 2012; 366: 687-696Crossref PubMed Scopus (1720) Google Scholar However, how much surveillance is required for the effectiveness of colonoscopy overall and in low- and high-risk patients still needs to be determined. NPS surveillance was tracked for up to only 6 years after polypectomy. We have shown in a microsimulation modeling analysis that there is a greater impact on postpolypectomy incidence reduction from the initial polypectomy than from surveillance.26Zauber A. Winawer S. Loeve F. et al.Effect of initial polypectomy versus surveillance polypectomy on colorectal cancer incidence reduction: microsimulation modeling of National Polyp Study Data.Gastroenterology. 2000; A187: 1200Google Scholar,27Meester R.G.S. Lansdorp-Vogelaar I. Winawer S.J. et al.High-intensity versus low-intensity surveillance for patients with colorectal adenomas: a cost-effectiveness analysis.Ann Intern Med. 2019; 171: 612-622Crossref PubMed Scopus (6) Google Scholar The NPS CRC mortality analysis supported the hypothesis that colonoscopic removal of adenomatous polyp prevents CRC that is potentially fatal and is therefore of clinical importance.5Zauber A.G. Winawer S.J. O'Brien M.J. et al.Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths.N Engl J Med. 2012; 366: 687-696Crossref PubMed Scopus (1720) Google Scholar This report helped increase public awareness of the benefit of screening and surveillance colonoscopy with removal of adenomas.28Grady D. Report affirms lifesaving role of colonoscopy. New York Times, 2012https://www.nytimes.com/2012/02/23/health/colonoscopy-prevents-cancer-deaths-study-finds.htmlDate accessed: September 11, 2020Google Scholar,29A test in time. New York Times, 2012https://www.nytimes.com/2012/02/25/opinion/a-test-in-time.htmlDate accessed: September 11, 2020Google Scholar Demonstration by the NPS of a mortality reduction after colonoscopic polypectomy invited the question of whether screening colonoscopy with removal of adenomas would similarly reduce CRC mortality. RCTs of screening colonoscopy compared with control subjects or fecal immunochemical test results will address this.24Bretthauer M. Kaminski M.F. Løberg M. et al.Population-based colonoscopy screening for colorectal cancer: a randomized clinical trial.JAMA Intern Med. 2016; 176: 894-902Crossref PubMed Scopus (148) Google Scholar,25Aronsson M. Carlsson P. Levin L. et al.Cost-effectiveness of high-sensitivity faecal immunochemical test and colonoscopy screening for colorectal cancer.Br J Surg. 2017; 104: 1078-1086Crossref PubMed Scopus (22) Google Scholar,30Quintero E. Castells A. Bujanda L. et al.Colonoscopy versus fecal immunochemical testing in colorectal-cancer screening.N Engl J Med. 2012; 366: 697-706Crossref PubMed Scopus (571) Google Scholar,31Dominitz J.A. Robertson D.J. Ahnen D.J. et al.Colonoscopy vs. Fecal Immunochemical Test in Reducing Mortality From Colorectal Cancer (CONFIRM): rationale for study design.Am J Gastroenterol. 2017; 112: 1736-1746Crossref PubMed Scopus (40) Google Scholar A family history of CRC in first-degree relatives is associated with an increased risk of CRC, especially in younger people in prospective studies32Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (633) Google Scholar and case-control studies.33St John D.J. McDermott F.T. Hopper J.L. et al.Cancer risk in relatives of patients with common colorectal cancer.Ann Intern Med. 1993; 118: 785-790Crossref PubMed Scopus (323) Google Scholar Given that the adenoma is considered to be the precursor lesion for CRC, whether family members of adenoma patients would be associated with an increased risk of CRC warranted further exploration. We asked in the NPS whether first-degree relatives of patients with adenomas would have an increased risk for CRC compared with spouse control subjects. We therefore conducted a retrospective cohort study in the NPS and assessed the cumulative risk of CRC in cohorts of siblings and parents to that of a cohort of spouses. The CRC status for family members and spouses was obtained from the adenoma patients. This ensured that knowledge of the CRC status was equivalent among both family members and spouses alike. Adenoma patients who were referred for colonoscopy because of family history of CRC were excluded from these analyses. The cumulative CRC risk was increased for siblings and parents of the adenoma probands compared with the spouse control subjects, especially when the adenoma proband was diagnosed before the age of 60 (Fig. 4). The results from family members of the adenoma patients replicated that of Fuchs et al32Fuchs C.S. Giovannucci E.L. Colditz G.A. et al.A prospective study of family history and the risk of colorectal cancer.N Engl J Med. 1994; 331: 1669-1674Crossref PubMed Scopus (633) Google Scholar and St John et al33St John D.J. McDermott F.T. Hopper J.L. et al.Cancer risk in relatives of patients with common colorectal cancer.Ann Intern Med. 1993; 118: 785-790Crossref PubMed Scopus (323) Google Scholar in family members of CRC cases. The NPS data provided the initial rationale that a premalignant polyp identified in a proband at a young age increased the CRC risk of first-degree relatives who should begin screening at a younger age and by colonoscopy. Recent evidence20Gupta S. Lieberman D. Anderson J.C. et al.Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Am J Gastroenterol. 2020; 115: 415-434Crossref PubMed Scopus (18) Google Scholar indicated that the advanced adenoma is the significant familial risk determinant rather than a nonadvanced adenoma.34Ng S.C. Lau J.Y. Chan F.K. et al.Risk of advanced adenomas in siblings of individuals with advanced adenomas: a cross-sectional study.Gastroenterology. 2016; 150 (quiz e16-7): 608-616Abstract Full Text Full Text PDF PubMed Scopus (18) Google Scholar,35Ng S.C. Kyaw M.H. Suen B.Y. et al.Prospective colonoscopic study to investigate risk of colorectal neoplasms in first-degree relatives of patients with non-advanced adenomas.Gut. 2020; 69: 304-310Crossref PubMed Scopus (5) Google Scholar The 2017 Multi-Society Task Force on CRC screening recommended that an individual with a first-degree relative with an advanced adenoma or CRC should begin screening at age 40 years.19Rex D.K. Boland C.R. Dominitz J.A. et al.Colorectal cancer screening: recommendations for physicians and patients from the U.S. Multi-Society Task Force on Colorectal Cancer.Gastroenterology. 2017; 153: 307-323Abstract Full Text Full Text PDF PubMed Scopus (257) Google Scholar This is important, but a family history of a pathology-documented advanced adenoma is often difficult to ascertain. Guidelines should also emphasize that increased risk screening should be recommended in first-degree relatives of patients who had an advanced adenoma resected. Because of its greater safety and lower costs, the double-contrast barium enema (DCBE) was considered appropriate for postpolypectomy surveillance and was used clinically in the 1970s. No blinded comparison of the 2 modalities (DCBE and colonoscopy) had been reported. A prospective comparison of DCBE and colonoscopy was incorporated into the NPS in which the endoscopist withdrew the endoscope by colonic segments and reported observations to a coordinator who knew the DCBE findings but the endoscopist was “blinded” to the DCBE report. If the DCBE was positive and the colonoscopy negative, an “unblinded reexamination” of the segment was done.4Winawer S.J. Stewart E.T. Zauber A.G. et al.A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. National Polyp Study Work Group.N Engl J Med. 2000; 342: 1766-1772Crossref PubMed Scopus (501) Google Scholar DCBE detected only one-third of the adenomas and missed half of the adenomas larger than 1 cm found on colonoscopy. The results reduced the value of DCBE in postpolypectomy surveillance, in screening, and in the diagnostic workup of patients with a positive stool occult blood test or flexible sigmoidoscopy.36Fletcher R.H. The end of barium enemas?.N Engl J Med. 2000; 342: 1823-1824Crossref PubMed Scopus (38) Google Scholar Colonoscopy as the preferred surveillance and diagnostic test was incorporated into guidelines after this study.15Winawer S. Fletcher R. Rex D. et al.Colorectal cancer screening and surveillance: clinical guidelines and rationale-Update based on new evidence.Gastroenterology. 2003; 124: 544-560Abstract Full Text PDF PubMed Scopus (1920) Google Scholar The blinded, unblinded colonoscopy in the NPS also enhanced the quality of the examination because the endoscopist was aware that a DCBE had been done approximately 2 weeks before the colonoscopy and that the results would be unblinded by the coordinator. Additional colonoscopy quality measures included cecal landmark identification and segmental and total colon clearance by the endoscopist based on optimal visualization and adequacy of preparation. Repeat colonoscopy to clear all polyps and reach the cecum was done in 13% of randomized patients. The high quality of colonoscopy was critical to CRC prevention.2Winawer S.J. Zauber A.G. Ho M.N. et al.Prevention of colorectal cancer by colonoscopic polypectomy. The National Polyp Study Workgroup.N Engl J Med. 1993; 329: 1977-1981Crossref PubMed Scopus (3642) Google Scholar,4Winawer S.J. Stewart E.T. Zauber A.G. et al.A comparison of colonoscopy and double-contrast barium enema for surveillance after polypectomy. National Polyp Study Work Group.N Engl J Med. 2000; 342: 1766-1772Crossref PubMed Scopus (501) Google Scholar Newly introduced examinations could be evaluated using the NPS blinded/unblinded design. One such test, CT colonography, was compared with colonoscopy for the detection of polyps by using the NPS segmental blinded/unblinded model.37Johnson C.D. Chen M.H. Toledano A.Y. et al.Accuracy of CT colonography for detection of large adenomas and cancers.N Engl J Med. 2008; 359: 1207-1217Crossref PubMed Scopus (822) Google Scholar,38Pickhardt P.J. Choi J.R. Hwang I. et al.Computed tomographic virtual colonoscopy to screen for colorectal neoplasia in asymptomatic adults.N Engl J Med. 2003; 349: 2191-2200Crossref PubMed Scopus (1646) Google Scholar The model can also be used to evaluate the accuracy of newer methods for colon examination. The NPS postpolypectomy model was also used in several primary prevention studies that would otherwise require large cohorts followed for a long time to evaluate CRC incidence and mortality. The NPS design, randomizing a smaller cohort into intervention and control groups with advanced adenomas as the endpoint, was adopted as a more feasible alternative by many studies. Assessed interventions included fiber, calcium, celecoxib, and aspirin.39Bertagnolli M.M. Eagle C.J. Zauber A.G. et al.Celecoxib for the prevention of sporadic colorectal adenomas.N Engl J Med. 2006; 355: 873-884Crossref PubMed Scopus (875) Google Scholar The cohort size permitted by the available funding for the NPS did not permit a large enough study in which CRC could be an outcome measure. Therefore, we needed to identify an intermediate CRC surrogate outcome measure. The studies by Muto et al11Muto T. Bussey H.J. Morson B.C. The evolution of cancer of the colon and rectum.Cancer. 1975; 36: 2251-2270Crossref PubMed Scopus (1802) Google Scholar suggesting that adenoma size and villous pathology correlated with concomitant CRC was the basis of our decision to incorporate an advanced adenoma as a CRC surrogate measure. In 1990 the NPS reported a statistical analysis of the pathologic characteristics of adenomas accrued to the study database that demonstrated a stepwise progression of risk for prevalent high-grade dysplasia, the precursor to invasive adenocarcinoma, that correlated independently with increasing size and acquisition of a villous component. This provided a further underpinning for the concept of the advanced adenoma having villous features or large size or high-grade dysplasia as a surrogate outcome measure.6O'Brien M.J. Winawer S.J. Zauber A.G. et al.The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas.Gastroenterology. 1990; 98: 371-379Crossref PubMed Scopus (690) Google Scholar We incorporated the advanced adenoma as an outcome measure in the NPS design in 1977 based only on the cross-sectional relationship of adenoma pathology with CRC.11Muto T. Bussey H.J. Morson B.C. The evolution of cancer of the colon and rectum.Cancer. 1975; 36: 2251-2270Crossref PubMed Scopus (1802) Google Scholar Atkin et al’s report in 1992,21Atkin W.S. Morson B.C. Cuzick J. Long-term risk of colorectal cancer after excision of rectosigmoid adenomas.N Engl J Med. 1992; 326: 658-662Crossref PubMed Scopus (897) Google Scholar which reported follow-up data on the relationship of rectosigmoid adenoma pathology to subsequent CRC, further validated the advanced adenoma as a surrogate cancer indicator. With the benefit and CRC risk provided by the NPS, the research environment changed. Larger studies were funded. However, what is needed are long-term studies of varying surveillance intensity to better elucidate the surveillance required for low- and high-risk patients. The EPoS is one such study14Jover R. Bretthauer M. Dekker E. et al.Rationale and design of the European Polyp Surveillance (EPoS) trials.Endoscopy. 2016; 48: 571-578Crossref PubMed Scopus (64) Google Scholar that when completed can inform the relationship of the advanced adenoma to CRC as an outcome measure and as a continued valid screening goal. In this RCT, the EPoS included both nonadvanced and advanced adenomas and the cancer outcome observations for shorter and longer surveillance intervals.14Jover R. Bretthauer M. Dekker E. et al.Rationale and design of the European Polyp Surveillance (EPoS) trials.Endoscopy. 2016; 48: 571-578Crossref PubMed Scopus (64) Google Scholar When the NPS was underway, flat adenomas and serrated polyps were not in the endoscopist’s or pathologist’s lexicon of polyps. However, a retrospective review of the archived pathology allowed us to document the prevalence and associated findings of these new entities among the cohort. Neither the sessile serrated polyp nor the flat adenoma was associated with a higher rate of high-grade dysplasia in synchronous or metachronous adenomas.6O'Brien M.J. Winawer S.J. Zauber A.G. et al.The National Polyp Study. Patient and polyp characteristics associated with high-grade dysplasia in colorectal adenomas.Gastroenterology. 1990; 98: 371-379Crossref PubMed Scopus (690) Google Scholar,9O’Brien M.J. Winawer S.J. Zauber A.G. et al.Flat adenomas in the National Polyp Study: Is there increased risk for high-grade dysplasia initially or during surveillance?.Clin Gastroenterol Hepatol. 2004; 2: 905-911Abstract Full Text Full Text PDF PubMed Scopus (120) Google Scholar This is being further evaluated.14Jover R. Bretthauer M. Dekker E. et al.Rationale and design of the European Polyp Surveillance (EPoS) trials.Endoscopy. 2016; 48: 571-578Crossref PubMed Scopus (64) Google Scholar,20Gupta S. Lieberman D. Anderson J.C. et al.Recommendations for follow-up after colonoscopy and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer.Am J Gastroenterol. 2020; 115: 415-434Crossref PubMed Scopus (18) Google Scholar The NPS introduced the postpolypectomy surveillance model and proved that removing adenomas prevented lethal CRC. This provided the rationale for guidelines to recommend screening colonoscopy, for RCTs to be initiated to study its effectiveness, and for the goal of CRC screening to focus on both CRC prevention and detection of early-stage CRC. The NPS model demonstrated that the lengthening of postpolypectomy surveillance intervals was safe and effective, which provided the rationale for guidelines to recommend less-frequent and risk-based surveillance and for RCTs to be initiated for further study of safety and effectiveness. This has become increasingly critical considering the proliferation of screening worldwide with the use of higher-definition endoscopes with quality benchmarks and with the dual goal of screening (prevention and early detection), which has resulted in a large population of patients that require surveillance. The sequence of strong scientific studies of both screening and surveillance followed by evidence-based clinical guidelines is critical to address continued challenges to CRC control.23Winawer S.J. The history of colorectal cancer screening: a personal perspective.Dig Dis Sci. 2015; 60: 596-608Crossref PubMed Scopus (38) Google Scholar
Referência(s)