An Evidence Based Approach to Colorectal Cancer Screening

1. An Evidence Based Approach to Colorectal Cancer Screening J. C. Ryan, M.D. Associate Professor of Medicine UCSF and SF VAMC 9/22/2014

2. Colorectal Cancer • Lifetime incidence of 6% • Common cause of cancer death, 2nd in men, 3rd in women • Well defined precursor lesion (adenoma) with long lag time until the development of cancer • Reasonable target for screening

3. USPSTF CRC Screening Recommendations • Colonoscopy q10 yr • Flex Sig q5 yr • Fecal Testing q1 yr • Flex Sig q5 yr and FOBT q1 yr • ACBE/CT colography q5 yr

4. Colonoscopy of Asymptomatic Patients 37.7% have colorectal neoplasia: 27% TA <10 mm 5% TA >10 mm 3% Villous adenoma 1.7% High grade dysplasia/CIS 1.0% Invasive cancer

5. Screening Sigmoidoscopy • Will detect 70% of patients with colonic neoplasia • Distal adenomas on sig prompt colonoscopy • 30% of patients (with only right sided neoplasia) will be missed • Will reduce cancer from 6% to 2% in the population

6. Colon Cancer Risk Reduction • Colonoscopy: 6% to <0.5% • Flex Sig: 6% to 2.0% • Fecal Occult blood?

7. HemoccultTesting • Minnesota, 1994 NEJM: 33% improved cancer survival • UK, 1997 NEJM: 15% improved cancer survival • Denmark, 1997 NEJM: 18% improved cancer survival

8. Theoretical test 99.5% sensitive and specific • 1000 pts from high risk (50%) population: • 500 true pos, 5 false pos • Predictive value 500/505 • 1000 pts from low risk (0.5%) population: • 5 true pos, 5 false pos • Predictive value 5/10

9. Similar test, 90% sensitive and specific • 1000 pts from high risk population: • 500 true pos, 100 false pos • Predictive value 500/600 = 83% • 1000 low risk patients: • 5 true pos, 100 false pos • Predictive value 5/105 = 4%

10. Performance characteristics of FOBT? • Noncolonoscopically controlled trial in patients with advanced neoplasia: • Up to 79.4% sensitive with select tests (NEJM. 334:155.1996) • Noncolonoscopically controlled trial in largely symptomatic cancer pts: • 66% sensitivity (Ann Int Med.112:328.1990)

11. FOBT 66-79% Sensitive? • Trials did not focus on asymptomatic patients? (not average risk) • Not colonoscopically controlled (Only FOBT+ patients were colonoscoped) • “Those with great enthusiasm have no controls and those with great controls have no enthusiasm”

12. Colonoscopically Controlled Trials of Hemoccult II • Imperiale, et al, NEJM. 351:2704. 2004 -Lieberman. NEJM. 345:555. 2002

13. Fecal blood testing (Hemoccult II) • Essentially random test that is positive leads to colonoscopy 6% of the time • Over 10 yr, [1- (0.94)10] = (1 - 0.53) = 47% of patients eventually will be FOBT+ and receive colonoscopy • 2.5% of SFVA patients aged 50-75 every year get a symptom generated colonoscopy (25% over 10 yrs) • Total colonoscopies over 10 yr period is approx 71% in FOBT screening programs

14. Screening Resources per 10,000 Patients/10 yr • CF Program (20% refuse screening): • 8,000 (80%) total naïve colonoscopies (screening and symptom generated) • Annual FOBT 6% positive rate: • 76,896 x 3 = 230,688 FOBT tests • 4,620 colonoscopies for +FOBT over 10 yr • 2500 symptom generated colonoscopies (screened nonetheless) over 10 yr • 7120 (71%) total naïve colonoscopies

15. Is Hemoccult II useful in conjunction with Flex sig? • Flex Sig alone: • 70.3% of pts with neoplasia detected • Flex Sig plus one time FOBT: • 75.8% of pts with neoplasia detected • 5.0% more colonoscopies needed to detect the additional 5.5% of patients (Lieberman, NEJM 2002)

18. All Studies

19. Studies with: Colonoscopic controlsAsymptomatic screening age patients

20. Varying the FIT Cutoff Alters Cancer Specificity

21. Only: Colonoscopic controlsAsymptomatic screening age patients FIT positive <10%

22. Hi Quality FIT Studies

23. Colonoscopy • Nearly 100% sensitive for the detection of cancer, 91% for polyps • National Colon Polyp Study predicts that colonoscopy will diminish colon cancer risk from 6% to <0.5% and will prevent death from colon cancer

24. Cost per year of life saved • Flex Sig every 5 yr $23K • Flex Sig plus annual FOBT $80K • FOBT annually $80-220K • Colonoscopy every 10 years $5.6K • Dialysis $55K • Mammography $80-140K? • Pap Smears $70-120K • Air bags $450K

25. SF-VAMC GI Unit44,000 screening age pts • 1994: Commitment to CF strategy • 1996: Only 57 screening colonoscopies • 1998: Direct screening and 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

26. CRC at the SF-VAMC • 1995-2000: 486 (81 cases/year) • 2001: 52 cases • 2002: 26 cases • 2003: 16 cases • 2004: 11 cases • 2005: 13 cases Total 118 cases

27. SF VAMC CRC 2001-2005 • 118 cases, 108 of whom were from our minority (21%) unscreened population • 10 cases occurred in our previously screened (79%) surveillance population • 7 had villous elements in index polyps • 3 had delayed colonoscopic surveillance

28. Conclusions • Endoscopic screening methods (Colon and Flex Sig) are acceptable methods for CRC prevention • Fecal testing is beneficial in that it prompts a screening colonoscopy • Fecal testing does not reduce colonoscopy demands and Hemoccult-II misses >87% of colon cancers in screening patients • Practitioners who use Fecal testing as primary screening have been successfully sued for missed cancers • The majority of positive fecal tests do not have advanced neoplasia (false positive)

29. Special Consult Considerations • Request for colonoscopy in patient with FOBT+ despite negative screening colon 2 yr ago. No anemia or symptom.

30. Special Consult Considerations • Request for colonoscopy in patient with FOBT+ despite negative screening colon 2 yr ago. No anemia or symptom. • If the majority of positive FOBT+ are false positive, nearly all positive FOBT in those with up to date colonoscopy are false positive • Recommendation: “Please discontinue Fecal testing”

31. Special Consult Considerations • Request for colonoscopy in patient with negative screening colon 2 yr ago because his spouse was dx’ed with CRC and he is “worried” about cancer. No anemia or symptoms.

32. Special Consult Considerations • Request for colonoscopy in patient with negative screening colon 2 yr ago because his spouse was dx’ed with CRC and he is “worried” about cancer. No anemia or symptoms. • Recommendation: Please tell this patient not to worry anymore. A complication from an unindicated colonoscopy is very difficult to defend!

33. 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.

34. 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

35. Special Consult Considerations • Request for colonoscopy due to new onset recurrent hematochezia over 2 months. Patient with screening colon 2 yr ago showing no neoplasia. Hct 36 no other symptoms. • Recommendation: Repeat colonoscopy to look for missed lesions

36. Acknowledgements • Ann Hayes, R.N. and Ken McQuaid, M.D. • The nurses of the San Francisco VA GIDC