Virtual Colonoscopy to Screen for Colorectal Cancer

1. Virtual Colonoscopy to Screen for Colorectal Cancer Lawrence Fleming, M.D. June 23, 2004

2. Computed Tomographic Virtual Colonoscopy to Screen for Colorectal Neoplasia in Asymptomatic Adults • Perry J. Pickhardt, M.D. is the lead author; Dr. Pickhardt is now in the Department of Radiology at UW. • N Engl J Med 2003;349:2191-2200. The December 4, 2003 issue.

3. Pickhardt et al, N Engl J Med 349;23 • Background • Evaluated the performance characteristics (sensitivity, specificity, negative predictive value) of computed tomographic virtual colonoscopy (VC) for the detection of colorectal neoplasia in an average-risk screening population.

4. Pickhardt et al, N Engl J Med 349;23 • Methods • 1233 asymptomatic adults underwent same-day virtual, then optical colonoscopy. • For the initial examination of each colon segment, the colonoscopists were blind to the findings on virtual colonoscopy taht were then revealed before subsequent reexamination.

5. Pickhardt et al, N Engl J Med 349;23 • Methods • The sensitivity and specificity of virtual colonoscopy and the sensitivity of optical colonoscopy were calculated using the findings of the final, unblinded optical colonoscopy as the reference standard.

6. Pickhardt et al, N Engl J Med 349;23 • The Study Group • Adults between 50 and 79 years old with an average risk of colorectal cancer and adults 40 to 79 years old with a family history of colorectal cancer. • Between May 2002 and June 2003, 1233 asymptomatic adults at three medical centers underwent same-day virtual colonoscopy followed by optical colonoscopy.

7. Pickhardt et al, N Engl J Med 349;23 • The Study Design • Patients underwent standard 24-hour colonic preparation with oral administration of 90 ml of sodium phosphate (Fleet Prep Kit 1) and 10 mg of bisacodyl. Patients also consumed 500 ml of barium for solid stool tagging and 120 ml of Gastrografin for opacification of luminal fluid. • After the insertion of a small flexible rectal catheter, pneumocolon was achieved through patient-controlled insufflation (auto-insufflation) of room air prior to scanning.

8. Pickhardt et al, N Engl J Med 349;23 • The Study Design • Commercially available CT colonographic software (Viatronix V3D Colon) extracted the CT images of the air-filled colon, generated a center line for luminal navigation, and electronically removed from the opacified residual fluid. • The diagnostic interface allows a virtual “fly-through” tour of the three-dimensional image and the rapid correlation with the two-dimensional images for any suspected abnormality (the three-dimensional images were used for the initial detection of polyps).

9. Pickhardt et al, N Engl J Med 349;23 • The Study Design • Polyps were measured with electronic calipers on the three-dimensional view and recorded according to the segment (cecum, ascending colon, hepatic flexure, transverse colon, splenic flexure, descending colon, sigmoid colon, or rectum). • Extracolonic findings on CT were also recorded and categorized as representing a finding of potentially high, moderate, or low clinical importance.

10. Pickhardt et al, N Engl J Med 349;23 • The Study Design • CT virtual colonoscopy studies were interpreted prospectively by one of six board-certified radiologists immediately before the optical colonoscopy.

11. Pickhardt et al, N Engl J Med 349;23 • The Study Design • Seventeen experienced colonoscopists (14 gastroenterologists and 3 colorectal surgeons) who were initially unaware of the findings of the virtual colonoscopy performed the optical colonoscopies. • A colonoscope was passed to the cecum and sequentially withdrawn segment by segment for the detection of polyps.

12. Pickhardt et al, N Engl J Med 349;23 • The Study Design • After the colonoscopist completed the examination of a segment, the study coordinator revealed the results of the virtual colonoscopy for that segment.

13. Pickhardt et al, N Engl J Med 349;23 • The Study Design • If a polyp of 5 mm or larger in diameter was seen on virtual colonoscopy but not on the initial optical examination of the segment, the colonoscopist closely reexamined the segment and was allowed to review the virtual colonoscopy images for guidance. • This “segmental unblinding” created an enhanced reference standard and allowed the assessment of false negative results on optical colonoscopy that would have otherwise been recorded as false positive on virtual colonoscopy.

14. Pickhardt et al, N Engl J Med 349;23 • The Study Design • Patients were asked to complete and return a one-page questionnaire that assessed the levels of discomfort as well as preference for virtual or optical colonoscopy in the future.

15. Pickhardt et al, N Engl J Med 349;23 • Statistical Analysis • The final results of the optical colonoscopy, which included findings after the reexaminations informed by the results of virtual colonoscopy, served as the reference standard with which the results of virtual colonoscopy and the initial colonoscopy were compared.

16. Pickhardt et al, N Engl J Med 349;23 • Results • Of 1253 consecutively enrolled asymptomatic adults, 1233 underwent complete virtual and optical colonoscopic examinations. • Based on the findings of unblinded optical colonoscpy, the prevalence of adenomatous polyps 10 mm or more in diameter was 4.1%, the prevalence of adenomatous polyps 8 mm or more in diameter was 6.7%, and the prevalence of adenomatous polyps 6 mm or more in diameter was 13.6%.

17. Pickhardt et al, N Engl J Med 349;23 • Results • 2 of the 554 adenomatous polyps (0.4%) were malignant • 1 of the 966 (0.1%) of the diminutive polyps (5 mm or less in diameter) was classified as advanced (a 4 mm tubular adenoma with villous features).

18. Pickhardt et al, N Engl J Med 349;23 • Results • Sensitivity of virtual colonoscopy was 93.8% for polyps at least 10 mm in diameter, 93.9% for polyps at least 8 mm in diameter, and 88.7% for polyps at least 6 mm in diameter. • Sensitivity of optical colonoscopy was 87.5% for polyps at least 10 mm in diameter, 91.5% for polyps at least 8 mm in diameter, and 92.3% for polyps at least 6 mm in diameter.

19. Pickhardt et al, N Engl J Med 349;23 • Results • The specificity of virtual colonoscopy was 96.0% for polyps at least 10 mm in diameter, 92.2% for polyps at least 8 mm in diameter, and 79.6% for polyps at least 6 mm in diameter. • The negative predictive value of virtual colonoscopy was more than 99% for polyps that were 8 mm or more in diameter.

20. Pickhardt et al, N Engl J Med 349;23 • Results • The summation of the true positive and false positive rates with virtual colonoscopy yields a “test positive rate.” This metric is dependent on the size category. If the cutoff had been 10 mm, 1 of every 13.4 patients or 7.5% would have been sent for optical colonoscopy; if the cutoff had been 6 mm, 29.7% would have been sent for optical colonoscopy.

21. Pickhardt et al, N Engl J Med 349;23 • Results • There were extracolonic findings on CT of potentially high importance in 56 patients (4.5%). Unsuspected extracolonic cancer was proven in five patients (0.4%). Two patients subsequently underwent repair of unsuspected abdominal aortic aneurysms.

22. Pickhardt et al, N Engl J Med 349;23 • Results • 1005/1233 patients returned the post-study questionnaire (81.5%). • More patients reported greater discomfort with virtual colonoscopy (546 patients, 54.3%) than with optical colonoscopy (383 patients, 38.1%). 76 patients or 7.6% were undecided or reported equivalent discomfort with the two studies.

23. Pickhardt et al, N Engl J Med 349;23 • Results • 82 patients (8.2%) rated the discomfort associated with virtual colonoscopy as severe. • More patients indicated they would prefer virtual colonoscopy to optical colonoscopy for future screening: 500/1005 patients (49.8%) preferred virtual colonoscopy, 413/1005 patients (41.1%) preferred optical colonoscopy, 92/1005 patients (9.2%) had no preference or were undecided.

24. The Polyp Size Controversy • Current “Standard of Practice” • There appears to be consensus (or at least a majority opinion) that diminutive polyps (less than 5 mm in diameter) should be considered clinically insignificant and therefore ignored on virtual colonoscopy.

25. The Polyp Size Controversy • The number of asymptomatic patients who would undergo virtual colonoscopy for screening but would not require optical colonoscopy for polypectomy is dependent on the size threshold chosen. At a threshold of 6 mm, 70.3% of patients would not have been sent for immediate polypectomy, at a threshold of 8 mm, 86.5% would not have been sent for immediate polypectomy, and at a threshold of 10 mm, 92.5% would not have been sent for immediate polypectomy.

26. Other Information Radiation exposure with VC is roughly equivalent to the amount of natural background radiation received in 1-2 years depending where one lives.

27. Other Information Screening VC candidates should be 50-79 years old and have no personal history of inflammatory bowel disease and no personal or family history of colon cancer. For information and scheduling of VC, call Deb Jones, RN, VC Coordinator at 608.263.9630.

28. Other Information GI has recruited three additional gastroenterologists and aims to provide prompt screening colonoscopy to patients age 50-79 years with a personal history of polyps or a family history of colon cancer. For information and scheduling of optical colonoscopy call 608.263.8094.

29. Other Information What will happen if polyps are found on VC? 5 mm or less- no additional immediate study 6-9 mm- IRB approved protocol to either proceed with optical colonoscopy or periodic surveillance with virtual colonoscopy (patient choice) 10 mm or greater- same-day or next-day optical colonoscopy for removal