David Lieberman

Lecture Abstract

 

Topic: Screening the General Population

Introduction

Colorectal cancer (CRC) remains the second leading cause of cancer death in North America, and the 4th most common cancer cause of death globally.  There is strong evidence that screening can reduce mortality and incidence of CRC.  Screening uptake in the United States has now reached 50% of individuals over age 50 years, and we are beginning to see a decline in annual incidence (1).  Two updated CRC screening guidelines were published in 2008 (2-4), from the American Cancer Society, Multi-Society Task Force on CRC, and the American College of Radiology (ACS-MSTF-ACR) and the United States Preventive Services Task Force (USPSTF).  The recommendations are summarized in Table 1.

 

Table 1: USA Colorectal Cancer Screening Guidelines - 2008

 

Screening Test                 ACS/MSTF/ACR                                              USPSTF   

gFOBT                                  YES, requires >50% Sensitivity                       YES, "sensitive" test only
                                             for CRC

FIT*                                       YES, requires >50% sensitivity                        YES
                                             for CRC

Stool DNA                             YES, requires >50% sensitivity                        NO; insufficient evidence
                                             for CRC

Flexible
Sigmoidoscopy                     YES                                                                   YES

Barium enema                      YES, but only if other tests                               Not recommended
                                             not available

CT Colonography                 YES                                                                    NO; insufficient evidence

Colonoscopy                        YES                                                                    YES

               

The ACS-MSTF-ACR guideline distinguishes between tests designed primarily for early cancer detection (fecal blood and DNA tests) and tests designed to detect both adenomas and early cancers (imaging and endoscopy), and recommends that patients be informed of the primary goals of the test.  The sensitivities of one-time testing for cancer and advanced adenomas (defined as adenoma >10mm, villous histology, high-grade dysplasia) are summarized in Tables 2A and B. 

 

Table 2A: Sensitivity of Stool-Based Tests


                                                          Sensitivity (one-time test)
                                                          Cancer                                Advanced Adenomas

Standard gFOBT (8-10,12,13)           33-50%                                11%

Sensitive gFOBT (11,12)                   50-75%                                20-25%

FIT (14-16)                                         60-85%                                20-50%

Stool DNA-old (13)                             51%                                      18%

Stool DNA- new (12,17)                    80+%                                    40%

  

Table 2B: Sensitivity of Structural Colon Exams

                                                           Sensitivity (one-time test)
                                                           Cancer                                                Advanced Adenomas

CT Colonography                               Uncertain                                           90% if >10mm

                                                          Likely >90%                                       *80-85% if based on histology

Sigmoidoscopy                                  >95% Distal Colon                              70%      

                                                           60-70% Proximal Colon

Colonoscopy                                      >95%                                                   88-98%

 

* CTC detection of all advanced adenomas, including adenomas <10mm with villous histology, high-grade dysplasia or cancer. 


Some advantages and limitations of each of the tests are summarized in Table 3A and 2B.

 

Table 3: Population Screening: Advantages and limitations of CRC screening tests
A. Early Cancer Detection tests

Test                                      Advantages                                                      Limitations and Uncertainties

gFOBT

(sensitive test only)

- Low initial cost

- Can be performed at home

- Requires few specialized resources

1. Not specific for human hemoglobin

2. One-time testing has limited sensitivity for cancer (Table 3) so that repeat testing needed every 1-2 years

3. Adherence to repeat testing unknown

4. Adherence to receiving colonoscopy for (+) test may be poor

5.Potential for cancer prevention limited due to poor sensitivity for advanced adenomas (Table 2)

FIT

- Specific for human hemoglobin

- Low initial cost

- Can be performed at home

1. Uncertain benefit compared to less costly sensitive gFOBT

2. One-time testing has limited sensitivity for cancer (Table 3) so that repeat testing needed every 1-2 years

3. Performance of new versions of test uncertain

4. Ideal number of stool samples uncertain

5. Potential for cancer prevention limited due to poor sensitivity for advanced adenomas (Table 2)

Stool DNA

- Detection of specific mutations may be more accurate than detection of blood

- Can be performed at home

 

1. Costly

2. Performance of new versions of the test uncertain

3. Appropriate intervals for repeat testing unknown

4. Potential for cancer prevention limited due to poor sensitivity for advanced adenomas (Table 2)

 

  

Table 3: Population Screening: Advantages and limitations of CRC screening tests 
               B. Tests which detect both cancer precursors and early cancer

Test                                      Advantages                                                      Limitations and Uncertainties

Imaging: CT

- High sensitivity for detection of lesions >10mm

-Less invasive than endoscopy

1. Requires bowel prep, special resources and expertise

2. Cost and risk depend on rate of referral for colonoscopy and frequency of evaluation for extra-colonic findings

3. Management of patients with polyps <6mm is uncertain

4. Detection of flat polyps uncertain

5. Radiation exposure

6. Appropriate intervals unknown

7. Quality in clinical practice unknown

Sigmoidoscopy

- Office-based; does not require sedation

- 60% reduction in mortality of cancers of the distal colon in case-control studies

1. No protection for proximal CRC

2. May be less effective with increasing age because of higher rates of proximal CRC

3. May be less effective in women

Colonoscopy

- 90% sensitivity for lesions >10mm

- Detection and removal of lesions during one exam

1. Evidence for reduction in CRC incidence and mortality is indirect

2. Requires bowel prep, special resources and expertise

3. High initial cost

4. Invasive with risk of serious complication in 3-5/1000 exams

5. Quality in clinical practice unknown

 

  

  

Key References:

  • 1. Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer Statistics 2008. CA Cancer J Clin 2008; 58: 71-96
  • 2. Levin B, Lieberman DA, McFarland B, Andrews KS, Brooks D, Bond J, Dash C, Giardiello FM, Glick S, Johnson D, Johnson CD, Levin TR, Pickhardt P, Rex DK, Smith RA, Thorson A, Winawer SJ. Screening and surveillance for early detection of colorectal cancer and adenomatous polyps, 2008:A joint guideline from the American Cancer Society, the US Multi-Society Task Force on Colorectal Cancer, and the American College of Radiology. Gastroenterology 2008; 134: 1570-95
  • 3. U.S. Preventive Services Task Force. Screening for colorectal cancer: U.S. Preventive Services Task Force Recommendation Statement. Ann Intern Med 2008; 149: 627-37
  • 4. Whitlock EP, Lin JS, Liles E, Beil TL, Fu R. Screening for colorectal cancer: A targeted, updated systematic review for the U.S. Preventive Services Task Force. Ann Intern Med 2008; 149: 638-58

 

 

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