Preventive Medicine (Cancer Screening & Immunizations) in Adults

1. Preventive Medicine(Cancer Screening & Immunizations) in Adults Michael Adams, M.D., FACP Program Director Assistant Professor of Medicine Georgetown University Medical Center

2. Cancer screening: Definitions Breast cancer Cervical cancer Colorectal cancer Prostate cancer Skin cancer Chemoprevention Controversies Vaccinations Outline

3. Definitions Screening: • testing for disease in average (or low) risk, asymptomatic population • may be considered a form of primary prevention • goals: • early detection • treating to reduce morbidity or mortality • no diagnostic intent • average prevalence (by definition)

4. Definitions Case-finding: • testing in patients at higher risk • patients seeking medical care because of a complaint • patients with familial risks / exposures / other diagnosis • may be a form of secondary prevention • disease present, reduce mortality / recurrence rate • diagnostic intent • usually higher than average disease prevalence

5. Operating characteristics • high sensitivity • low burden • early detection • ability to modify course of disease • higher prevalence = better positive predictive value

6. GUIDELINES • ACP, USPSTF, CTF, NCI, NIH, AMA, ACC, AHA, AUA, ACOG, IOM • USPSTF • evidence-based • frequent updates • factor in net benefit, quality of the evidence

7. US Preventive Services Task Force (USPSTF) • http://www.ahcpr.gov/clinic/uspstfix.htm

8. USPSTF Ratings • Recommendation: A - routinely provide to eligible patients. The USPSTF found good evidence that [the service] improves important health outcomes and concludes that benefits substantially outweigh harms. • Recommendation: B - routinely provide to eligible patients. The USPSTF found at least fair evidence that [the service] improves important health outcomes and concludes that benefits outweigh harms.

9. USPSTF Ratings • Recommendation: C - no recommendation for or against routine provision of [the service] At least fair evidence that [the service] can improve health outcomes but concludes that the balance of the benefits and harms is too close to justify a general recommendation. • Recommendation: D - recommends against routinely providing [the service] to asymptomatic patients The USPSTF found at least fair evidence that [the service] is ineffective or that harms outweigh benefits.

10. USPSTF Ratings • Recommendation: I - evidence is insufficient to recommend for or against Evidence that [the service] is effective is lacking, of poor quality, or conflicting and the balance of benefits and harms cannot be determined.

11. Breast Cancer • North America: leading cancer in women, 2nd leading cause of cancer death • 2001: 192,000 diagnoses, 40,200 deaths • >50%: no known major predictors • Risk increases with age, atypical hyperplasia • BRCA-1 and -2 BRCA-1 BRCA-2 breast breast ovary ovary colon colon? prostate prostate? male breast? male breast pancreatic?

12. Breast Cancer: mammography • Sensitivity 56-95% • Lower in younger, dense breasts, HRT • Specificity 94-97% • More false positives (less specific) in younger women • Abnormal mammogram & chance of cancer: • 40-49: 2-4% PPV • 50-59: 5-9% • 60+: 7-19%

13. Breast Cancer: Clinical Breast Exam • Sensitivity 40-69% • Specificity 86-99% • 4% of patients with abnormal CBE diagnosed with cancer in a large community trial • These trials compared CBE with mammography, mortality trials use both CBE & mammogram

14. Breast Cancer: age considerations • Most screening trials 50-69 • 40-49: weaker evidence, delay in benefit (lower prevalence in younger women) • Interval for screening is unknown • Over 70: • evidence generalized unless comorbid conditions reduce life expectancy • Higher absolute risk of cancer • Mammography benefits (absolute) increase with age • Mammography risks (RELATIVE) diminish with age

15. Breast Cancer • The (USPSTF) recommends screening mammography, with or without clinical breast examination (CBE), every 1-2 years for women aged 40 and older. B recommendation

16. Breast Cancer: CBE • The USPSTF concludes that the evidence is insufficient to recommend for or against routine CBE alone to screen for breast cancer. “I” recommendation

17. Breast Cancer: Self Breast Exam • Sensitivity 26-41% • Specificity unknown • No known mortality difference • Risks of abnormal self exam (anxiety, testing, biopsy)

18. Breast Cancer: self-exam • The USPSTF concludes that the evidence is insufficient to recommend for or against teaching or performing routine breast self-examination (BSE). “I” recommendation

19. Breast Cancer: other considerations • Patient preferences, clinical judgment • Family history • BRCA • Other organizations have varying recommendations: • Yearly after age 40: AMA, ACOG, ACS, ACR • Yearly after 50: CTF, AAFP, ACPM • Interval varies (q1, q2 between 40-49) • BSE: ACOG, ACS, AMA, AAFP favor teaching

20. Cervical Cancer • 13,000 cases yearly • 4,100 deaths (2002) • Risks: • early intercourse • increased # of sexual partners • smoking • HPV (95-100% of squamous cell CA of cervix)

21. Cervical Cancer • Natural history of HPV – slow transition to cancer • “orderly fashion from less severe to more severe dysplasia” • Not faster in HIV+ women (prevalence higher) • Every 6-12 months • Younger women: HPV may be transient • Older women: higher chance of progression to cancer • PAP smear: 60-80% sensitive • New technologies (“ThinPrep”): no good data yet

22. Cervical Cancer – HPV testing • Sensitivity 82% • Specificity 78% • Benefits untested • 8 ongoing studies

23. Cervical Cancer - timing • Interval: every 3 years after 2-3 normals • Sensitivity 60-80% for high grade lesions for a single PAP test • ACS: wait until age 30 to extend screening interval • Annual screening: cervical neoplasia, HPV, other STDs, high risk sexual behavior • Cessation of screening • Low predictive value for women over 65 (ACS: 70), no abnormal PAP in past 10 years • Hysterectomy for benign disease (only cancer in 1995 study of 10,000 PAP smears was vaginal squamous cell CA)

24. Cervical Cancer • The USPSTF strongly recommends screening for cervical cancer in women who have been sexually active and have a cervix. A recommendation

25. Cervical Cancer • The USPSTF recommends against routinely screening women older than age 65 for cervical cancer if they have had adequate recent screening with normal Pap smears and are not otherwise at high risk for cervical cancer. D recommendation

26. Cervical Cancer • The USPSTF recommends against routine Pap smear screening in women who have had a total hysterectomy for benign disease. D recommendation

27. The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of human papillomavirus (HPV) testing as a primary screening test for cervical cancer. The USPSTF concludes that the evidence is insufficient to recommend for or against the routine use of new technologies to screen for cervical cancer. Cervical Cancer “I” recommendation “I” recommendation

28. ASC-H = atypical squamous cells suspicious for HSIL

30. Colorectal Cancer • 4th most common cancer in US • 2nd leading cause of cancer death • At age 50, 5% risk of being diagnosed with colon cancer • Adenomatous polyps – precursor • Hereditary polyposis syndromes (FAP, HNPCC) – 6% of all colon cancers

31. Colorectal Cancer - DRE • Little evidence • Sensitivity much less than multiple test cards • False negatives – no stool in vault • False positives – rectal trauma • Therefore, not recommended as a tool for colorectal cancer screening

32. Colorectal Cancer - FOBT • sensitivity 26 - 92%, specificity 90-99% • 3 samples, rehydrated cards improve sensitivity (diminishes specificity) • Annual screening has detected 49% of incident cancers • FOBT: 33% reduction in mortality over controls • inexpensive

33. Colorectal Cancer - sigmoidoscopy • Alone: • detects approximately 7 cancers and 60 large polyps/1000 exams • estimated detection of significant colonic lesions of 80% • Sigmoid abnormalities often trigger colonoscopy • Combination with FOBT: • detects 65-75% of polyps and 40-65% of cancers • reduces mortality by 60% • detects an additional 7 cancers over FOBT alone

34. Colorectal Cancer - DCBE • Limited studies: sensitivity 86-90% for cancer / polyps • Only 48% sensitive for polyps > 1cm in National Polyp Study • Specificity 85% • No outcome data

35. Colorectal Cancer - colonoscopy • Sensitivity 90% for large polyps, 75% for small polyps • Specificity difficult to define • Minority of patients who have polypectomy would have developed cancer • PROS: view entire colon, ability to biopsy/treat during procedure • CONS: cost, complications, prep/discomfort

36. Colorectal Cancer - colonoscopy • The effectiveness of colonoscopy to prevent colorectal cancer or mortality has not been tested in a randomized clinical trial.1 • Comparisons with historical controls: estimates 76-90% reduction in cancers. 1USPSTF website: http://www.ahcpr.gov/clinic/3rduspstf/colorectal/colorr.htm

37. Colorectal Cancer – CT colography (“virtual colonoscopy”) • Non-invasive • 10-15 minutes • 85-90% sensitive in research setting • Prep still necessary • No outcome data • New software?

38. Colorectal Cancer - costs • Costs for screening, 2002 • Stool hemoccult $7-10 • Flexible sigmoidoscopy $176-299 • Colonoscopy $670-981 excluding facility fee Among 6 high-quality cost-effectiveness analyses examining only direct costs, the average cost-effectiveness ratio values for screening adults older than 50 with each of the major strategies were under $30,000 per life-year saved (Year 2000 dollars). Studies varied as to which strategy was most cost-effective, however. (USPSTF)

39. Colorectal Cancer • The USPSTF strongly recommends that clinicians screen men and women 50 years of age or older for colorectal cancer. A recommendation

40. Colorectal Cancer • Other considerations: • Family history of colon cancer <60: test earlier • “The choice of screening strategy should be based on patient preferences, medical contraindications, patient adherence, and resources for testing and followup.” (USPSTF) • Timing (American Cancer Society) • FOBT: yearly • Sigmoid: every 5 years • DCBE: every 5 years • Colonoscopy: every 10 years • (One-in-a-lifetime after age 55)

41. Prostate Cancer • 2nd leading cause of cancer death among men in US • 2002: 189,000 new cases • Risk increases with age (6.5% by age 60) • Ethnic differences (mortality): • Asian/Pacific Islanders: 1.0 • Latino/Hispanic 1.08 • White 1.67 • Black 3.33 • Black men have higher incidence rate • Most men will not die of their disease (3% out of 15%)

42. Prostate Cancer • Considerations: • DRE, PSA accuracy • DRE: <60% sensitivity, operator-dependent • PSA: 60-80% sensitive using 4.0 as abnormal • Early detection • Mortality benefit? • Scant evidence, some showing reduced deaths from prostate cancer after prostatectomy but complications not considered • Complications of treatment • Age of patient • Screening is most likely to benefit the following: • 50-70 year old men at average risk • Men over 45 with risk factors (Black men, Family hx)

43. Prostate Cancer - USPSTF • “Despite the absence of firm evidence of effectiveness, some clinicians may opt to perform prostate cancer screening for other reasons.   Given the uncertainties and controversy surrounding prostate cancer screening, clinicians should not order the PSA test without first discussing with the patient the potential but uncertain benefits and the possible harms of prostate cancer screening. Men should be informed of the gaps in the evidence, and they should be assisted in considering their personal preferences and risk profile before deciding whether to be tested.”

44. Prostate Cancer • Prostate cancer guidelines • USPSTF: do not recommend screening • ACS, AUA, AAFP, AMA: consider DRE at age 40, PSA over 50 (40 for Black men) • CTF: recommend against PSA, do not recommend discontinuation of DRE • ACP: do not recommend screening • All groups advise physicians to give information to patients about screening, risk/benefit, treatment & individualize testing

45. Prostate Cancer • The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routine screening for prostate cancer using prostate specific antigen (PSA) testing or digital rectal examination (DRE). “I” recommendation

46. Skin Cancer • The U.S. Preventive Services Task Force concludes that the evidence is insufficient to recommend for or against routine counseling by primary care clinicians to prevent skin cancer. “I” recommendation

47. Skin Cancer • The U.S. Preventive Services Task Force (USPSTF) concludes that the evidence is insufficient to recommend for or against routine screening for skin cancer using a total-body skin examination for the early detection of cutaneous melanoma, basal cell cancer, or squamous cell skin cancer. “I” recommendation

48. Chemoprophylaxis for Neoplastic Diseases • tamoxifen and raloxifene may prevent some breast cancers in women at low or average risk for breast cancer • tamoxifen can significantly reduce the risk for invasive ER-positive breast cancer in women at high risk for breast cancer and that the likelihood of benefit increases as the risk for breast cancer increases • raloxifene – consistent evidence (fewer studies)

49. Chemoprophylaxis – side effects • VTE • Symptomatic side effects (hot flashes) • Endometrial cancer (tamixofen only) • Need to balance harms vs benefits

50. Variable Age 45 Age 55 Age 65 Age 75 5-year risk of breast cancer, %    No Family history 0.7 1.1 1.5 1.6    Family history 1.6 2.3 3.2 3.4 Benefits per 1,000 women of 5 y of tamoxifen Cases of invasive breast cancer avoided, n    No Family history 3-4 5-6 7-8 8    Family history 8 11-12 16 17 Cases of noninvasive breast cancer avoided, n    No Family history 1-2 2 2-3 2-3    Family history 2-3 3-4 4-5 5-6 Hip fractures avoided, n <1 3 5 15 Harms per 1000 women of 5 y of tamoxifen Cases of endometrial cancer caused, n 1-2 12 21 "22" Strokes caused, n 1 3 9 20 Pulmonary emboli caused, n 1-2 4-5 9 18 Cases of DVT caused, n 1-2 1-2 3 4