1. AIMGP Seminar Series January 2004 Joo-Meng Soh Edited by Gloria Rambaldini CANCER SCREENING PART II

2. OBJECTIVES Understand the concept of cancer screening and the controversies surrounding this topic To learn the Canadian screening guidelines for Breast and Colorectal cancer To be aware of other cancer screening guidelines available

3. Principles of Cancer Screening Screening of asymptomatic individuals to detect early cancers which may be curable Use of diagnostic tests of high sensitivity Diagnostic tests are suitable to the patient Natural history of disease can be changed by intervention Proposed early treatment should be beneficial and not harmful to the patient

4. Case #1 While on Team Medicine, you make the diagnosis of metastatic breast cancer in your 47 year old female patient You think to yourself, “I wonder if she did Breast Self Examinations? Should she have received a mammogram? Would her cancer have been picked up earlier? Could she have been cured?”

5. Guidelines Available

6. Breast Cancer Most frequently diagnosed cancer in women In 2001, estimated: –19,200 cases diagnosed –5,500 deaths –2 nd leading cause of cancer death in women (after lung CA) Canadian Cancer Statistics 2001 http://66.59.133.166/stats/index.html http://66.59.133.166/stats/index.html

7. Breast Cancer Statistics Risk of being Diagnosed with Breast Cancer Risk of Dying from Breast Cancer: 1 in 25

8. Screening Maneuvers Breast Self Examination (BSE) Clinical Breast Examination (CBE) Mammography

9. Potential Benefits Detection of Tumour at earlier stage Improved Cosmetic result if found early Reassurance if negative screening test

10. Potential Harms Radiation-induced Carcinoma from mammography –Est. risk of death from this is 8 per 100,000 women screened annually for 10 years beginning at age 40 Unnecessary biopsies Psychological stress of call-back Possible false reassurance

11. RCTs for BSE No reduction in breast cancer mortality or stage at diagnosis seen in two large scale on-going RCTs Shanghai Trial (n=267 040 women) –Aged 31-64 –Results after first 5 years of follow-up Russian/WHO Trial (n=122 471 women) –Aged 40-64 –Results after first 5 and 9 years of follow-up

12. Breast Self-Examination ON THE OTHER HAND...... RCTs showed a significant increase in: –number of physician visits for the evaluation of benign breast lesions –breast biopsy rates for benign lesions

13. Breast Self Examination (BSE) 1994 Canadian Task force on Preventive Health Care made BSE a Class C recommendation (insufficient evidence to recommend for or against BSE) Due to recent trials, this screening tool now down-graded to class D (fair evidence to recommend that BSE be excluded from the periodic health exam)

14. CBE & Mammography For Women Aged 50 - 69 HIP (Health Insurance Plan) Trial –RRR of 0.55 in breast ca. mortality over 5 yrs Swedish Trials –RRR of 0.29 in breast ca. mortality over 7-12 years follow-up Canadian Trial comparing mammography over CBE –RRR of 0.03 (NS) at 7 years follow-up

15. Breast Cancer Screening with both CBE and mammography should be done for women aged 50-69 annually (Grade A Recommendation) CBE & Mammography For Women Aged 50 - 69

16. CONFLICTING RESULTS!!! Only one RCT designed specifically for women aged 40-49 did not have adequate power to exclude a clinically sig. benefit Other RCT results are from post hoc subgroup analyses CBE & Mammography For Women Aged 40 - 49

17. RRR of 18%-45% in breast cancer mortality at 10 years shown in 2 trials and 1 meta-analysis No benefit was shown in 6 other trials Recommendations: –Evidence does not support the use or exclusion of mammography for the periodic health exam in women aged 40-49 (Grade C) CBE & Mammography For Women Aged 40-49

18. Back to the Case “I wonder if she did BSEs” –Not currently recommended “Should she have received a mammogram” –Unclear at this point in time; Women aged 40- 49 should be informed of the risks and benefits of screening mammography and then assisted in making a decision” “Would her cancer have been picked up earlier? Could she have been cured?” –Possibly....

19. OTHER Guidelines  AAFP - American Academy of Family Physicians  ACOG - American College of Obstetricians and Gynecologists  ACS - American Cancer Society  CTFPHC Canadian Task force on Preventive Health Care  NIH - National Institutes of Health  USPSTF - U.S. Preventive Services Task Force

20. Case #2 During your GI rotation you consult on a 54 year old male with newly diagnosed metastatic colon cancer Your team debates whether screening could have detected the cancer earlier? Although the GI fellow swears by colonoscopies you wonder ‘what about all the hype regarding fecal occult testing vs sigmoidscopes vs barium enemas vs virtual c-scopes vs…”

21. Guidelines Available

22. COLORECTAL CANCER Third most common cancer in Canada In 2001, Estimated –New cases: 17,200 –Deaths: 6,400 Canadian Cancer Statistics 2001 http://66.59.133.166/stats/index.html http://66.59.133.166/stats/index.html

23. Screening Tools Fecal Occult Blood Testing Sigmoidoscopy Barium Enema Colonoscopy

24. Fecal Occult Blood (FOB) Rationale – detect occult blood from cancers or large polyps 3 consecutive stool samples at home Evidence from 4 large-scale RCTs Overall Sensitivity  25 - 50% False positive rate  10% Overall benefits are statistically sig. but small Number needed to screen for 10 years to avert one death from colorectal cancer = 1173

25. Sigmoidoscopy May reduce the risk of death from Colorectal cancer (3 case control studies) 3 RCTs suggest it may be superior in detecting adenomas and possibly cancer than FOBT (but no mortality data) Potential Harms: –Bowel perforation in 1.4 per 10,000 exams

26. Colonoscopy Currently no direct evidence on mortality benefit from colonoscopy as a screening maneuver Potential Harms: –Bowel perforation in 10 per 10,000 exams

27. Comparison of all Three Recent NEJM article: Aug. 23, 2001 “One-Time Screening for Colorectal Cancer with Combined FOBT and Examination of the Distal Colon”, Lieberman D et al n = 2885 patients All patients provided stool for FOBT, then underwent Colonoscopy (“sigmoidoscopy” was defined as examination of the rectum and sigmoid colon during colonoscopy)

28. Comparison of all Three Only 23.9% of patients with advanced neoplasia had a positive FOBT Sigmoidoscopy identified only 70.3% of all subjects with advanced neoplasia Combined FOBT and sigmoidoscopy identified only 75.8% of subjects with advanced neoplasia In other words, combined FOBT and sigmoidoscopy would have missed  25% of the colorectal cancers

29. Canadian Recommendations Good evidence to include annual or biennial FOBT (Grade A Recommendation) Fair evidence to include Flexible Sigmoidoscopy (Grade B Recommendation) Insufficient evidence to make recommendations about whether only one or both tests should be performed (Grade C) Insufficient evidence to include or exclude colonoscopy as initial screening test Grade C) Colorectal Cancer Screening – Recommendations from the Canadian Task force on Preventive Health Care CMAJ 2001; 165(2): 206 - 208

30. Other Guidelines  AAFP- American Academy of Family Physicians  ACOG- American College of Obstetricians and Gynecologists  ACS- American Cancer Society  AMA - American Medical Association  AGA - American Gastroenterological Association  CTFPHC - Canadian Task Force on Preventive Health Care  USPSTF - U.S. Preventive Services Task Force Outdated

31. MANEUVEREFFECTIVENESSLEVEL OF EVIDENCERECOMMENDATION Average Risk Multiphase screening with the Hemoccult test for average risk adults > age 50 Relative risk of CRC* death with screening with Hemoccult testing is 0.84 (95% CI 0.77-0.93) in those who are compliant NNT=1173 over 10 yrs Randomized controlled trials and meta-analyses Good evidence to include screening with annual or biennial Hemoccult test in the periodic health examination (PHE) of patients >50 Sigmoidoscopy for average risk adults > age 50 Patients with rectal cancers were less likely to have had a sigmoidoscopy in the previous 10 yrs Case-control studies, case series Fair evidence to include screening with flexible sigmoidoscopy in the PHE of patients > 50 Hemoccult/sigmoidoscopy in combination for average risk adults > age 50 Some evidence that the addition of flexible sigmoidoscopy increases the detection rate of adenomas and colorectal cancer. Nor mortality data RCTInsufficient evidence to make recommendations about whether only 1 or both of FOBT and sigmoidoscopy should be performed ColonoscopyIndirect evidence from RCT showing decreased colorectal cancer mortality RCTInsufficient evidence to include or exclude colonoscopy from PHE

32. Back to the Case Screening can result in the reduction in CRC related mortality Recommendations thus far include routine FOBT and sigmoidoscopy Routine colonoscopy is not supported by good evidence at present Like all screening tests…patient counseling will guide you and the patient

33. Other References Cancer Screening Guidelines, American Family Physician 2001, 63(6):1101-1112 –Summarizes in table format the guidelines published by multiple organizations Preventive Health Care, 2001 update: screening mammography among women aged 40-49 years at average risk of breast cancer, CMAJ 2001; 164(4): 469-76 Preventive Health Care, 20001 update: Should women be routinely taught BSE to screen for breast cancer, CMAJ 2001; 164(13): 1837-46