Latest Endoscopic Guidelines for FAP, HNPCC, IBD, and the General Population David T. Rubin, M.D. Assistant Professor of Medicine Inflammatory Bowel Disease Center MacLean Center for Clinical Medical Ethics The University of Chicago Medical Center 23 March 2007
Disclosure I have no conflicts of interest to report related to this presentation.
Learning Objectives Review the general principles of secondary prevention of colorectal cancer Understand the guidelines for endoscopic surveillance for colorectal cancer in average risk, familial, HNPCC, FAP and inflammatory bowel disease Define the paradigm for incorporation of future prevention technologies
Events Leading to Colon Cancer Targets for Prevention or Mortality Reduction Normal mucosa Aberrant Crypt Small adenoma Adenoma increasing in size and degree of dysplasia Carcinoma Metas tasis Chemoprevention Polypectomy Surgery/Adjuvant Therapy Chemotherapy
Colorectal Cancer Prevention Primary cancer prevention Chemoprevention Prophylactic colectomy in at risk individuals Secondary cancer prevention Identification of pre-cancerous lesions Removal of pre-cancerous lesions Prevention of progression to invasive cancer Preserve organs/avoid surgery Prolong inter-examination intervals Tertiary cancer prevention (CRC survivors) Reduce neoplasia recurrence
to Prevent CRC Polypectomy Dectection of Dysplaisa in IBD
Prevention of Colorectal Cancer Chemoprevention Lag Time Detectable Precancer Phase Birth Death Molecular Events Sensitivity Specificity Reproducibility Reliability Polyps Endoscopy Invasive Cancer Polypectomy or Surgery
Development of Prevention Guidelines Identification of Risks Development of Prevention Strategies Evidence-based Expert opinion Consensus statements Outcomes Mortality reduction Reduced cancer incidence Implementation
Society Guidelines Reviewed American Cancer Society 2006 American College of Gastroenterology 2004 American Gastroenterological Association 2003 American Society of Gastrointestinal Endoscopy 2006 American Medical Association/American College of Physicians (USHPSTF) Multisociety Task Force on Colorectal Cancer 2003, 2006 Crohn s and Colitis Foundation of America 2005 British Society of Gastroenterology 2002 European Society of Gastrointestinal Endoscopy Advisory Committee on Cancer Prevention (EU) 2000 Société Française d Endoscopie Digestive 2005
Average Risk Screening at age 50 Procedure FOBT Flex Sig Frequency Every 10 years Every year Every 5 years Societies ACG, ACS, AGA, ASGE ACG, ACS, AGA, ASGE Flex Sig Every 5 years ACS, AGA, ASGE FOBT DCBE Every year Every 5 years ACS, AGA, ASGE, ACCP ACS
Screening Programs by Nation Nationwide program Program advocated Reimbursement Documentation of findings Austria () * Germany Italy () * - Luxemburg - - Poland () * Portugal - - - - USA - - Pox C et al Endoscopy. 2007;39:168-173. * Partially in place
Age-Adjusted Cancer Death Rates, 1930-2003 U.S. SEER Data Males Females Jemal, et al CA Cancer J Clin 2007;57:43-66
1 st Degree Relative with CRC 1 st Degree Relatives with CRC Age Procedure Frequency Society 1 by age 60 OR >1 at any age 40, or 10 years prior to earliest CRC in family Every 3-5 years ACG, AGA, ASGE 1 after age 60 40 years Follow average risk guidelines (ASGE prefers colonoscopy) ACG, AGA, ASGE
1st Degree Relative with CRC 1 st Degree Relatives with CRC Age Procedure Frequency Society 1 by age 45 35-40 Once BSG 55 Follow average risk guidelines > age 45 50 Follow average risk guidelines BSG
1 st Degree Relative with Adenoma 1 st Degree Relatives with Adenomas Age Procedure Frequency Society Advanced adenomas OR Adenomas by 60 40, or 10 years before earliest adenoma OR Individualize Dependent on family history etc Every 5 years ASGE AGA Adenomas after 60 Individualize Dependent on family history etc AGA, ASGE
Polyp Surveillance Previous Polyps Follow-up Procedure Society Small rectal hyperplastic polyps 10 years ACS < 2 small adenomas 5-10 years ACS, AGA, ASGE, BSG 3-10 adenomas 3-5 years ACS, AGA, ASGE, BSG >10 adenomas OR adenoma >1cm <3 years ACS, AGA, ASGE >5 adenomas OR adenoma >1cm 1 year, then every 3 years BSG
Familial Adenomatous Polyposis Mutation Status Age Procedure Frequency Society Proband Patient OR Proband 10-15 years Polyposis phenotype Flex Sig Surgery Every 1-2 years ACG, AGA, ASGE, BSG Proband Patient - 13-15 years 40 years Flex sig Every 7-10 years Every 5 years ASGE All FAP patients By age 25 Upper Endoscopy/Side Viewing scope ACS, AGA, ASGE
Hereditary Non-Polyposis Colorectal Cancer Mutation Status Age Procedure Frequency Society Proband Patient OR Proband Meets criteria 20-25 years Polyposis phenotype Surgery Every 1-2 years ACG, AGA, ASGE, BSG Criteria or mut with gastric phenotype 50 or 5 years before youngest gastric ca EGD Every 2 years BSG
Improves Survival of Genetically-Confirmed HNPCC 100 Survival n=133 Surveillance (q 3y) No surveillance 92.2% 80 n=119 73.9% 60 40 0 5 10 Järvinen HJ et al. Gastroenterol. 2000;118:829-34 Follow-up time (years) 15
Inflammatory Bowel Disease Patient Age Procedure Frequency Society Pancolitis, Left-sided colitis 8-10 years after onset with biopsies Every 1-2 years ACG, AGA, CCFA Escalate with disease duration BSG UC PSC Time of PSC diagnosis with biopsies Every year ACG, AGA, CCFA, BSG
Evidence for Surveillance in IBD Study Surveillance Outcomes of CRC No Surveillance Statistics Karlen 1998 2/40 deaths 18/102 deaths RR 0.28 95% CI 0.07-1.17 Choi 1993 15/19 Duke s A-B 5 yr survival 77.2% 9/22 Duke s A-B 5 yr survival 36.3% P=0.039 Lashner 1990 4/91 deaths 2/95 deaths RR 2.09 95% CI 0.39-11.12 Cochrane Systematic Pooled Analysis 8/110 deaths 13/117 deaths RR 0.81 95% CI 0.17-3.83 2004
What will Change Guidelines? Successful prevention will impact use of family history Improved optics Better markers and tools Quality issues in colonoscopy
withdrawal Time Correlates with Polyp Detection Methods: Prospective study of 7882 colonoscopies by 12 endoscopists Large community clinic Conclusions Adenoma detection varies by withdrawal time Effect on widespread screening unknown Time of withdrawal <6 minutes Detection rate Neoplasia 11.8% Advanced neoplasia 2.6% 6 minutes 28.3% 6.4% Barclay RL et al NEJM 2006;355:2533-41. P<0.001 P<0.005
Prevention of Colorectal Cancer Chemoprevention Detectable Precancer Phase Birth Death Molecular Events Novel Detection Neoplasia Endoscopy Invasive Cancer Polypectomy or Surgery
Summary Endoscopy is used for secondary prevention of CRC by identification of polyps or dysplasia in flat mucosa. Guidelines are similar among societies and are based on consensus, available evidence and the understanding of the pathogenesis of the disease as well as resource allocation. An emphasis on measurable quality and newer techniques and technologies will likely improve our prevention strategies. Additional outcomes studies and education of our colleagues is critical.