5/22/19 Colorectal Cancer An Evidence Based Approach to Colorectal - PDF document

5/22/19 Colorectal Cancer An Evidence Based Approach to Colorectal • Lifetime incidence of 6% Cancer Screening • Prevalence of 1% in asymptomatic patients aged 50-75 • Common cause of cancer death, 2nd in men, 3rd in women Jay Ryan, M.D. • Well defined precursor lesion (adenoma) with long lag time until the development of cancer Associate Professor of Medicine • Reasonable target for screening UCSF 5/22/2019 No Disclosures USPSTF CRC Screening Recommendations (2016) Tier 1 CRC Screening Tools • Colonoscopy screening every 10 yr • Adenomas on index colon prompt 3-5 yr surveillance colonoscopy • Polyp revoval prevents cancer • Reduces the lifetime incidence of CRC by 85-90% • Annual FIT screening • Measures human hemoglobin in stool sample • Positive tests prompt colonoscopy • FIT screening not indicated in those with up-to-date colonoscopy, known prior adenomas, or family history of CRC 1

5/22/19 Colonoscopy of Asymptomatic Patients Colonoscopy Aged 50-75 • Nearly 100% sensitive for the detection of cancer, 91% 37.7% have colorectal neoplasia: for polyps 27% TA <10 mm 5% TA >10 mm • National Colon Polyp Study and subsequent studies 3% Villous adenoma have shown that colonoscopy decreases colon cancer 1.7% High grade dysplasia/CIS risk from 6% to <0.5% and can prevent death from 1.0% Invasive cancer colon cancer Lieberman, NEJM, 2000 All screening tests are subjected to Performance characteristics of colonoscopy Bayesian constraints vs FIT in CRC screening? Colonoscopy: Gold Standard for polyp and cancer detection FIT: Newer test whose performance characteristics are being defined 2

5/22/19 Bayesian analysis: Theoretical test, 99.5% Bayesian analysis: Similar test, 90% sensitive sensitive and specific and specific • 1000 pts from high risk (50%) population: • 1000 pts from high risk population: – 500 true pos, 100 false pos – 500 true pos, 5 false pos – Predictive value 500/600 = 83% – Predictive value 500/505 • 1000 low risk patients: • 1000 pts from low risk (0.5%) population: – 5 true pos, 100 false pos – 5 true pos, 5 false pos – Predictive value 5/105 = 4% – Predictive value 5/10 Practical requirements of annual fecal Why a 6-8% fecal test positivity rate? screening tests for CRC • Over 10 yr [1- (0.94) 10 ] = (1 - 0.53) or 47% eventually will be positive and undergo colonoscopy • Highly sensitive for CRC and maybe for large polyps • 2.5% of screening patients every year undergo symptom generated colonoscopy (25% over 10 yrs) • Should reduce the need for colonoscopy • Should be <6-8% positive in asymptomatic screening • Total colonoscopies over 10 yr estimated at (47% + 25%) 72% in FIT screening programs aged individuals • HEDIS benchmark for screening is 71% 3

5/22/19 Sensitivity of FIT, Lee, et al Overall sensitivity of FIT for CRC was 77% in all included studies by Meta analysis Lee, et al, Ann Int Med 2014 4

5/22/19 2-y follow-up (91%) vs colonoscopy (71%) sensitive Exclude studies not examining asymptomatic, screening aged patients and those not using colonoscopic controls Varying the FIT Cutoff Alters Cancer Specificity Exclude studies not examining and the Percent Positivity asymptomatic screening aged patients and those not using colonoscopic controls Study Levi N 1204 Park N 770 DeWijk N 1256 (2007) (2010) (2012) Cutoff % Pos Adv Ad Cancer % Pos Adv Ad Cancer % Pos Adv Ad Cancer 50 17% NR 72% 14.2% 44.1% 12/13 (92.3%) 10% 35.4% 7/8 (88%) Exclude studies with 75 12.5% NR 67% 12.3% 37.3% 12/13 (92.3%) 6.6% 31% 6/8 (75%) FIT+ rates of over 10% 100 11.6% NR 61% 11.3% 33.9% 12/13 (92.3%) 5.6% 29.2% 6/8 (75%) 125 9.8% NR 53% 10% 28.8% 11/13 (84.6%) 150 9.4% NR 53% 7.9% 27.1% 11/13 (84.6%) Lee, Ann Int Med 2014 5

5/22/19 Hi Quality FIT Studies: Positive <10%, screening age, colonoscopically controlled Study N % Positive Sens AA Sens CRC Levi (2007) 1000 9.4% NR 53% Morikawa (2005) 21,805 5.6% 27.1% 65.8% Chiu (2013) 18,296 7.3% 28% 78.6% Brenner (2013) 2235 5.0% 23.4% 60.0% Brenner (2013) 2235 5.0% 20.4% 53.3% Brenner (2013) 2235 5.0% 25.7% 73.3% Lee, Ann Int Med 2014 16.2% Pos 7.0% Pos Incidence of Colonic Neoplasia by Group 6

5/22/19 Is colonoscopic screening feasible? SF-VAMC GI Unit 44,000 screening age patients • 1994: Commitment to colonoscopic screening strategy • 1996: Only 57 screening colonoscopies • 1998: Direct access scheduling by GI nurses • 1999: Telephone scheduling by GI nurses • 1999: Elimination of routine clinic visits for path FU • 1997-2003: Marked increase in exams for even minimal chronic symptoms ( de facto screening) • 2002-2005: Steady state reached at 76-79% with CRC screening from reminder data CRC Screening at the SFVAMC 1994-Present 25 Cancers in those with prior colonoscopy: 12 diagnosed outside surveillance interval Cancers 1998-2011 13 cancers Dx within surveillance interval: -4 recurrence at large polyp site -3 following normal colonoscopy at OSH -6 likely missed lesions at SFVA - 7

5/22/19 USPSTF CRC Screening Recommendations (2016) SFVAMC CRC Screening Results • Fecal testing has never been programmatically utilized at the SFVAMC • Efforts spent chasing down fecal tests have rather been spent improving GI unit efficiencies • Colonoscopic screening is currently in steady state at 83% among screening aged SFVAMC patients and is nearly completely protective from the development of CRC • Colon cancer at the SFVAMC is now vanishingly rare and the paucity of new diagnoses has resulted in multiple investigatory site visits by the US Inspector General Relative Costs: Tier 2 CRC screening options 80% colon acceptance 25% symptom generated colon/10 yr • Flexible sigmoidoscopy every 5 yr: Cost of colonoscopy is denoted by X • 70.3% sensitive for cancer, 70% sensitive for advanced adenomas • 70% sensitive for small adenomas • Prompt colonoscopy in 35% of cases in a 10 yr span • Colonoscopy every 10 yr: 0.8 colon (0.8X) 0.8X • Inexpensive test can be done by general practitioners • FIT every yr: 0.7 colon (0.7X) + FIT admin 0.8X + ca cost • CT Colography: 3D reconstruction of CT images every 5 yr • 84-91% sensitive for cancer, 70% sensitive for advanced adenomas • Cologuard every 3 yr: 0.7 colon (0.7X) + CG admin 0.8X + ca cost • Neither sensitive nor specific for small lesions <8 mm (considered negative!) • Flex Sig every 5 yr: 0.35 colon (0.35X) + 2 Flex (0.5X) 0.85X + ca cost • Prompt colonoscopy in 11-22% of cases in a 10 yr span • Expensive test with some radiation exposure • CT Colon every 5yr: 0.45 colon (0.45X) + 2 CT (1X) 1.45X + ca cost • Cologuard: Fecal DNA plus FIT every 3 yr: • 92% sensitive for cancer, 42% for advanced adenomas • No utility in the detection of small adenomas • False positives prompt colonoscopy in 45% of cases in a 10 yr span 8

5/22/19 Conclusions Special Consult Considerations • Among CRC screening strategies, direct colonoscopy is a practical screening method exhibits superior sensitivity, cancer prevention, and • Request for colonoscopy in patient with FIT+ despite resource utilization compared to other strategies negative screening colon 2 yr ago. No anemia or • Fecal testing does not appreciably reduce colonoscopy utilization but symptoms. delays its implementation, yet misses 30% of cancers. The vast majority of positive fecal tests are false positive. • CT colography is an expensive Tier 2 screening tool whose performance in real world studies has not been fully evaluated. • Flex Sig is falling out of favor but is likely better than Fecal Testing Special Consult Considerations Special Consult Considerations • Request for colonoscopy in patient with FIT+ despite • Request for colonoscopy in patient with negative negative screening colon 2 yr ago. No anemia or screening colon 2 yr ago because his spouse was symptoms. dx � ed with CRC and he is � worried � about cancer. No anemia or symptoms. • If the majority of positive FIT+ are false positive, nearly all positive FIT in those with up-to-date colonoscopy are false positive. • Recommendation: � Please discontinue Fecal testing � 9

5/22/19 Special Consult Considerations Special Consult Considerations • Request for colonoscopy due to new onset constipation or • Request for colonoscopy in patient with negative screening colon 2 yr ago because his spouse was a solitary episode of hematochezia. Patient with screening dx � ed with CRC and he is � worried � about cancer. No colon 2 yr ago showing no neoplasia. No anemia or other symptoms. anemia or symptoms. • Recommendation: Please tell this patient not to worry anymore. A complication from an unindicated colonoscopy is very difficult to defend! Special Consult Considerations • Request for colonoscopy due to new onset constipation or a solitary episode of hematochezia. Patient with screening colon 2 yr ago showing no neoplasia. No anemia or other symptoms. • Most CRC sx manifest in the distal colon. Recommend examine distal colon with Flex Sig 10