Screening and Surveillance for Colorectal Cancer

1
Screening and Surveillance for Colorectal Cancer

• Douglas K. Rex MD
• Chancellor's Professor and Professor of Medicine
• Indiana University School of Medicine
• Director of Endoscopy, Indiana University
  Hospital
• Indianapolis, Indiana

2
Objectives

• Understand screening options for average risk and
  high risk patients
• Know surveillance colonoscopy guidelines for
  persons with resected adenomas

3
Cost of Colorectal Cancer Screening vs Other
Medical Practices

• Colon cancer screening from age 55 years is
  cost-effective, but depends on compliance2

1Provenzale et al, Am J Gastroenterol 1999 94
268 2Lieberman et al, Gastroenterology 1995 109
1781
4
Adherence Rates Cancer Screening

• U.S. Adherence
  Rates
• Breast Cancer 69
• Cervical Cancer 86
• Prostate Cancer 75
• Colorectal Cancer 45 63
• Seeff Cancer 2002952211-22
• Sirovich JAMA 20032891414-20

5
Projected Annual Hospital Admissions for Colon
Cancer in the US 1990-2050
Number of admissions (thousands)
Year
Seifeldin and Hantsch, Clin Ther 1999 21 1370
6
Risk Stratification in Screening

• Usual Risk Factorsin Clinical Practice
• average risk (age gt 50)high risk (family history)

7
Average Annual Age-Specific US Incidence and
Mortality Rates of CRC
Number / 100,000 population
600 500 400 300 200 100 0
Incidence in menIncidence in women Mortality in
menMortality in women
30-34 35-39 40-44 45-49 50-54 55-59 60-64 65-69 70
-74 75-79 80-84 85
Age group (years)
Natl Cancer Inst, SEER Cancer Statistics Review
8
Factors Associated With CRC
Sandler, Gastroenterol Clin N Am 1996 27 717
9
African-Americans and CRC

• Younger mean age at diagnosis (60-66y)
• Higher incidence rates
• Higher mortality rates
• More proximal distribution of cancers and
  adenomas
• Ghafoor et al, CA Cancer J Clin, 2002 52 326
• Theuer et al, Gastroenterology, 2001 120 848
• Ries et al, http//seer.cancer.gov/csr/1975-2000

10

• What constitutes high risk is a matter of
  perception.

11
Medical-Legal Risk and Colorectal Cancer
Primary Care Physicians

• Traditional Source
• failure to evaluate rectal bleeding
• failure to evaluate positive FOBT
• New Source
• failure to screen

12

• Have a screening program in place in your
  practice
• Systematically offer the program to your patients
  and document

13
CRC Screening Guidelines

• ACS-MSTF-ACR
• Annual FOBT (now HOS or FIT)
• Flex sig every 5 yrs
• Combination of above
• DCBE every 5 years
• Colonoscopy every 10 years
• CT colonograhy every 5 years
• Fecal DNA (interval not stated)

14
US Preventive ServicesTask Force

• Grade A Recommendationfor colorectal cancer
  screening
• Optimal method of screening not clear
• Pignone, Ann Int Med 2002137129

15
ACG Screening Recommendations

• Average risk
• Preferred strategy
• colonoscopy q 10y
• Alternative strategy
• annual FOBT plus flex sig q 5y

Rex DK, Am J Gastroenterol 200095868-77
16
Patient Preferencesfor Screening Tests

• Unwilling to haveinvasive screening
• Encourage FOBT
• Leard, J Fam Pract 199745211

• Willing to haveinvasive screening
• COLONOSCOPY

17
Why Does Colonoscopy Dominate?

• Pros
• Most sensitive
• Long lasting protection
• Single session diagnosis and therapy
• Comfortable
• Rex, Am J Gastroenterol 200095868

• Cons
• Perceived as invasive
• Highest risk
• Requires bowel preparation
• Imperfect sensitivity

18
Four Largest Trials of CTC

• Author N pts Sens
  Sens
• gt9mm
  gt5mm
• Johnson 703 46
  52
• Pickhardt 1233 94
  89
• Cotton 615 55
  39
• Rockey 614 59

19
3D Multicenter Trial CT Colonography

• Multicenter military hospitals
• 1233 asymptomatic patients
• 10mm 8mm 6mm
• CT Sens AD by pt 94 94 89
• CC Sens AD by pt 88 92 92
• CT Specificity 96 92 80
• Pickhardt, NEJM 2003 349 2191

20
ACRIN trial

• US Multicenter study 2600 patients proven
  radiologists (top 75 of performers)
• 90 sensitivity for patients with large polyps (gt
  9 mm in size)
• 86-89 specificity for polyps gt 5mm
• PPV for polyps gt 9 mm 23
• No difference between 2-D and 3-D

21
CTC

• Even when effective multiple issues need to be
  addressed
• Adherence bowel prep issues
• Small polyp management
• Radiation risk from repeated studies
• Costs
• Rational approach to extra-colonic findings

22
Fecal DNA Testing - Rationale

• Cells with abnormal DNA shed continuously from
  surface of cancers and adenomas
• DNA stable in stool
• Abnormal DNA can be separated from normal human
  and bacterial DNA, amplified and identified by
  molecular tests

23
PreGen-Plus Process
Stool DNA AnalysisIs Performed in Lab and
Reported to Physician
PhysicianSendsRequisitionto Lab
Patient CollectsStool at Home
Lab ProvidesCollection and Shipping
Materialsto Patient
Patient ReturnsSpecimen to Lab
PhysicianCommunicatesResults to
Patient Mutation Identifiedperform
interventional colonoscopy No Mutation
Identified continue routine screening program
24
Benefits of PreGen-Plus

• Adherence
• No dietary, medication restrictions
• Single specimen needed
• Simple collection method
• No bowel preparation
• Quality control
• Centralized, automated processing

25
Fecal DNA Testing

• 5 targets K-RAS, P53, APC, BAT-26, long DNA
• Sensitivity for cancer 52
• Sensitivity of FOBT for cancer 13
• Sensitivity for advanced adenomas 18
• Specificity 94
• Imperiale et al, NEJM Dec 2004

26
Stool DNA Testing

• Version 1.0
• APC, K-ras, p53, BAT-26, DIA
• Version 1.1
• Gel based DNA capture
• DNA stabilization (buffer)
• Version 2.0
• Vimentin methylation
• DIA

27
PillCam COLON Capsule

• New PillCam design
• 2-sided video cameras 4 frames per second (fps),
  2 fps per camera
• 810 hours operating time

.
28
PillCam COLON Spectrum of Colon Disease
PillCam COLON is not cleared for marketing or
available for commercial distribution in the
United States 510(k) pending.
29
Tests to watch for

• Serum hypermethylation assays
• Tests for cancer (sensitivity probably in the
  range of 50-70) probably not high sensitivity
  for adenomas
• Specificity may be a problem
• Cost likely in range of 100
• High potential for adherence improvement
• Interval for performance uncertain
• Two under development

30
Family History Moderate Increased Risk

• Single first degree relative diagnosed at age ?
  60 years with cancer or adenoma
• Recommendation
• Begin screening age 40
• Options same as average-risk
• Winawer et al, Gastroenterology 2003124544
• Smith et al, CA A Cancer J Clin 20045441

31
Age and Cumulative Incidence of CRC10 Year
Shift With Positive Family History
Cumulative incidence (cases/10,000)
600 500 400 300 200 100 0
Family history(n 11,734) No family history(n
107,382)
30 35 40 45 50 55 60 65 70
Age (years)
Fuchs et al, N Engl J Med 1994 331 1669
32
Relative Risk of CRC in Families of Patients
With Adenomatous Polyps The Effect of Age of
Diagnosis
Relative risk in siblings of patients
50-59 yrs vs gt60 yrs
lt50 yrs vs gt60 yrs
p 0.005 n 1,199 patients, 4,246 first degree
relatives
Winawer et al, N Engl J Med 1996 334 82
33
High-Risk Family History

• Two or more first degree relatives with cancer
  or adenomas
• First degree relative with cancer or adenoma
  diagnosed at age lt 60 years
• Recommendation
• Begin screening at age 40 or 10 years younger
  than age at diagnosis of youngest affected
  relative
• Colonoscopy every 3-5 years
• Winawer et al, N Engl J Med 199633482
• Ahsan et al, Ann Intern Med 1998128900

34
Other High Risk Patients

• Risk Screening
• GYN cancer 3.5 colonoscopy q 5
• age lt 50y
• breast 1.1 same as average

Weinberg, Ann Int Med 1999131189 Schoen, Am J
Gastroenterol 199489835
35
High Risk Screening

• Consider genetic testing

36
HNPCC Clinical Features

• Modified Amsterdam Criteria
• 3 relatives with HNPCC related cancer (CRC,
  uterine, small bowel, renal pelvis or ureter)
• 2 generations affected
• 1 person diagnosed at age lt 50 y
• 1 person is a first degree relative of the other
  two

Vasen et al, Gastroenterology 1999 116 1453
37
HNPCC

• Amsterdam criteria neither sensitive or specific
• Bethesda criteria more sensitive
• Maintain high index of suspicion
• Screen tumors for MSI or
• Immunostaining for MMR gene products

38
Post-Polypectomy Surveillance

• Postpolypectomy (good prep, exam to cecum)
• Category Interval
• One or two TA lt 1cm 5 - 10 y
• 3-10 adenomas, any 3 yvillous component, HGD
• 10 or more adenomas lt3 y
• Large sessile adenoma 2-6 mo
• Large proximal colon HP clinical judgment

Gastroenterology 20061301872-85
39
Post-polypectomy Surveillance

• If follow up is normal or only small distal
  hyperplastic polyps
• Prior history Next
  follow-up
• only small TA 5-10 years
• Advanced adenoma 5 years

40
Post Colon Cancer Resection Surveillance

• Clear colon of synchronous disease
• First follow up colonoscopy 1 year
• If first follow up negative next exam in 3-5
  years
• If patient under 50 years consider closer
  intervals
• CEA every 2-3 mos first 2 years
• Consider annual liver CT (Renehan, BMJ 324813)

41
Post Rectal Cancer Resection Surveillance

• Best approach may depend on how the cancer was
  treated
• Lower local recurrence rates associated with
  Total Mesorectal Excision and with neoadjuvant
  radiation/chemotherapy
• Kapiteijn, NEJM 2001345638
• If risk of local recurrence high, consider flex
  sig or rectal EUS every 3 to 6 mos for first 2
  years
• Other surveillance same as for colon cancer

42
Future of Colonoscopy

• Increasing emphasis on quality performance cecal
  intubation rates, adenoma detection rates, use of
  recommended surveillance intervals
• Improvements in image quality (e.g. wide angle,
  high definition, cap fitted colonoscopy)
• Methods to determine real time histology of
  polyps narrow band imaging, confocal laser
  microscopy, chromoendoscopy with high
  magnification