An Evidence Based Approach to Colorectal Cancer Screening

J. C. Ryan, M.D.

Associate Professor of Medicine UCSF and SF VAMC

9/22/2014

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

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

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

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

Colon Cancer Risk Reduction

• Colonoscopy: 6% to <0.5%

• Flex Sig: 6% to 2.0%

• Fecal Occult blood?

HemoccultTesting

• Minnesota, 1994 NEJM: 33% improved cancer survival

• UK, 1997 NEJM: 15% improved cancer survival

• Denmark, 1997 NEJM: 18% improved cancer survival

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

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%

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)

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”

Colonoscopically Controlled Trials of Hemoccult II

–Imperiale, et al, NEJM. 351:2704. 2004 -Lieberman. NEJM. 345:555. 2002

Imperiale N = 2507 Std HC-II Lieberman N = 2885 Rehyd HC-II

Patient group FOBT+ FOBT- % Positive FOBT+ FOBT- % Positive

Total patients 144 2361 5.8% 239 2646 8.6%

No neoplasia 82 1702 4.6% 98 1559 5.9%

Adenoma <10 mm 15 271 5.2% 68 817 7.7%

Advanced adenoma 43 360 10.7% 61 258 23.4%

Cancer 4 27 12.9% 12 12 50%

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

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

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)

All Studies

Studies with: Colonoscopic controls

Asymptomatic screening age patients

Varying the FIT Cutoff Alters Cancer Specificity

Study Levi (2007)

N 1204 Park (2010)

N 770 DeWijk(2012)

N 1256

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%)

75 12.5% NR 67% 12.3% 37.3% 12/13 (92.3%) 6.6% 31% 6/8 (75%)

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%)

Only: Colonoscopic controls

Asymptomatic screening age patients

FIT positive <10%

Hi Quality FIT Studies

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%

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

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

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

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

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

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)

Special Consult Considerations

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

• 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”

Special Consult Considerations

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.

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!

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.

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

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

Acknowledgements

• Ann Hayes, R.N. and Ken McQuaid, M.D.

• The nurses of the San Francisco VA GIDC