1. Richard M. Hoffman, MD, MPH DOIM Thursday School October 30, 2014

2.  “But I’m admitting that American medicine has overpromised when it comes to screening. The advantages to screening have been exaggerated.” Otis Brawley, MD Chief Medical Officer American Cancer Society New York Times (10/21/09)

3.  Screening definition  Criteria for implementing screening  Evaluating the efficacy of screening  Critical review of prostate cancer screening  Evidence  Guidelines  USPSTF cancer screening recommendations

4.  Applying a diagnostic test to asymptomatic people to classify their likelihood of having a particular disease

5.  “Likelihood of disease”

6.  Persons with abnormal tests require further diagnostic studies  Gold standard tests usually invasive, riskier, and more expensive

7.  “Asymptomatic”

8.  Patient expectations  Screening helpful only if early detection and treatment is effective ▪ First do no harm (primum non nocere) ▪ Merely advancing the time of diagnosis is harmful (lead time)

9.  “Asymptomatic”  Target high-risk population ▪ Behaviors ▪ Smoking ▪ Risk factors ▪ Family history

10. Sporadic (65%–85%) + Family history (10%–30%) HNPCC (5%) FAP (1%) Rare syndromes (<0.1%) CDC

12.  “Asymptomatic”  Older age (> 50 years) ▪ 70+ million

13.  “Asymptomatic”  Expensive ▪ Screening ▪ Gold-standard diagnosis

14.  “Asymptomatic”  Policy decision ▪ Limited health care resources ▪ Competing demands

16.  Epidemiology  Natural history  Screening tests  Treatments

17.  Important clinical problem  Common  Substantial burden of suffering ▪ Impairs quality of life ▪ Hospitalizations ▪ Death

18.  Time course of disease  Long asymptomatic period to make early diagnosis

19.  Acceptable  Available  Accurate: valid and reproducible  Detects clinically important disease

20.  Acceptable  Available  Efficacious  Reduces disease-specific mortality and morbidity in randomized controlled trial

22.  Outcomes  Decreased disease mortality and morbidity ▪ Decreased incidence of advanced-stage disease ▪ Prevents disease (sometimes)

23.  Screening study designs  Randomized controlled trial: least biased  Observational ▪ Cohort ▪ Case-control

24.  Selection  Lead-time  Overdiagnosis bias  Length-time

25.  Healthy volunteer  Adherent  Worried well

26. ©2006 UpToDate® www.uptodate.com Licensed to University of New Mexico

27.  Failure to adjust for detecting “pseudo- disease”  Subclinical disease that would not have been detected during the person’s lifetime ▪ No chance of dying from the disease ▪ Survival time is misleading Welch HG. JGIM 1997;12:118

28. ©2006 UpToDate® www.uptodate.com Licensed to University of New Mexico

30.  2014 ACS estimates (men)  233,000 cases (1st)  29,480 deaths (2nd)  Lifetime risks  Diagnosis: 1 in 6  Death: 1 in 30 American Cancer Society. Cancer Facts & Figures 2014.

31.  Microscopic cancer (found with PSA testing) to clinical detection  5 to 15 year interval

32.  Prostate-specific antigen (PSA)  PPV: 30%  Digital rectal exam  PPV: 28%

33.  Randomized controlled trials  Surgery vs. watchful waiting: 2 studies ▪ RP effective for clinically detected cancers ▪ Only for men < 65 ▪ RP not effective for screen-detected cancers ▪ Possible benefit for high-risk cancers  Radiation vs. watchful waiting: 1 study ▪ No benefit Dahabrah IJ. Ann Intern Med 2012;156:582

34.  High burden of disease  Long asymptomatic stage  Available screening tests  Available treatments

35.  European Randomized Study of Screening for Prostate Cancer (ERSPC)  Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO)

36.  Randomized controlled trial of 182,160 men ages 50-74  7 European countries  Screening group  PSA every 4 years  Control group  Usual care Schröder FH. N Engl J Med 2009; 360:1320

37.  Biopsy referral  PSA > 3 ng/mL  Treatment  Local standards  Endpoints (9-year follow up)  Cancer incidence and mortality Schröder FH. N Engl J Med 2009; 360:1320

38.  Initial report  162,243 in core age group 55-69  Prostate cancer incidence  Screening: 8.2%  Control: 4.8% ▪ Rate ratio = 1.70 (95% CI, 1.64 – 1.77) Schröder FH. N Engl J Med 2009; 360:1320

39. Relative risk = 0.80 (95% CI 0.65 – 0.98)

40.  Relative risk reduction: 20%  Absolute risk reduction: 0.71 deaths/1000 men  Need to invite 1410 men to be screened twice over 9 years to prevent 1 PCa death  Need to diagnose 48 cancers to prevent 1 PCa death Schröder FH. N Engl J Med 2009; 360:1320

41.  Randomization methods, screening protocols, and biopsy criteria varied across countries and over time  Considered a meta-analysis ▪ Positive results only in Netherlands, Sweden

42.  Unable to exclude treatment effect  Control subjects with localized PCa, particularly with high-risk features, were less likely than screening subjects to receive radical prostatectomy—which is effective.  Control subjects more likely to receive androgen deprivation therapy—which is harmful. Wolters T. Int J Cancer 2010; 126:2387; Barry MJ. NEJM 2009;360:1351 Haines IE. J Natl Cancer Inst 2013;105:1534

43.  Randomized controlled trial of 76,685 men ages 55-74  Screening group  Annual PSA and DRE  Control group  Usual care Andriole GL. N Engl J Med 2009; 360:1310

44.  Biopsy referral  PSA > 4 ng/mL, abnormal DRE  Treatment  Local standards  Endpoints (7-year follow up)  Cancer incidence and mortality Andriole GL. N Engl J Med 2009; 360:1310

45. Rate ratio = 1.22 (95% CI, 1.16 - 1.29) Rate ratio = 1.13 (95% CI, 0.75 - 1.70)

46.  Prevalent screening  44% 1+ PSA tests within past 3 years  Contamination in control group  52% underwent PSA testing  36% of those with elevated baseline PSA not biopsied within 3 years (Pinsky PF. J Urol 2005;173:746)

47.  American Cancer Society (ACS)  American College of Physicians (ACP)  American Urological Association (AUA)  United States Preventive Services Task Force (USPTF)

48.  Shared/informed decision making  Address screening average-risk men at 50/55 ▪ 10- to 15-year life expectancy  DRE optional  Consider 2-year screening interval Wolf AMD. Ca Cancer J Clin 2010;60:70; Qaseem A. Ann Intern Med 2013;158:761; Carter HB. J Urol 2013;190:419

49.  Grade D recommendation  The USPSTF recommends against providing [PSA screening] to men without suspicious symptoms regardless of age, race, or family history  An individual man may choose to be screened. The decision should be an informed decision, preferably made in consultation with a regular care provider. Moyer VM. Ann Intern Med 2012;157:120

50.  Don’t ask, don’t tell (unless they ask)

51.  Complex decisions  Multiple acceptable options involving significant tradeoffs among different possible outcomes  Extensive effect on the patient  Controversial Braddock CH. JAMA 1999; 282:2313

52.  Elements required for complex decisions  Discuss ▪ Patient’s role in decision making ▪ Clinical issue or nature of decision ▪ Alternatives ▪ Potential benefits and harms of the alternatives ▪ Uncertainties associated with the decision Braddock CH. JAMA 1999; 282:2313

53.  Collaborative process that allows patients and their providers to make health care decisions together, taking into account the best scientific evidence available, as well as the patient’s values and preferences http://informedmedicaldecisions.org/

54.  PSA screening is controversial  For most men, chances of harms of screening outweigh chances benefits  Most prostate cancers are indolent  Most men, even if not screened, will not be diagnosed with or die from prostate cancer Qaseem A. Ann Intern Med 2013;158:761

55.  PSA testing increases risk of cancer diagnosis  PSA does not identify high-risk cancers  Small potential benefit  Many potential harms  Not “just a blood test” Qaseem A. Ann Intern Med 2013;158:761

56. Benefits (screening every 1 to 4 y for 10 y)Men, n 10-year PCa death no screening5 in 1000 10-year PCa death with screening4-5 in 1000 Net benefit0-1 in 1000 Harms (screening every 1 to 4 y for 10 y)Men, n False positive test100-120 in 1000 Prostate cancer diagnosis110 in 1000 Death (treatment)< 1 in 1000 Urinary incontinence (treatment)18 in 1000 Erectile dysfunction (treatment)29 in 1000 Moyer VA. Ann Intern Med 2012;157:120

57.  Shared decision making  Given the complexity of the issues involved and the time constraints faced by health care providers, we encourage providers and patients to use prostate cancer screening decision aids to facilitate the process Wolf AMD. Ca Cancer J Clin 2010;60:70

58.  Tools to support decision making when evidence is uncertain and/or very sensitive to patient preferences  Formats: written, video, interactive computer programs, Web-based Rimer BK. Cancer 2004; 101:1214. Barry MJ. Ann Intern Med 2002; 136:127

59.  Provide evidence-based information about a health condition, the options, associated benefits, harms, probabilities, and uncertainties O’Connor AM. Cochrane Database Syst Rev 2009;Jul 8;(3):CD001431

60.  Help patients to recognize the values- sensitive nature of the decision and clarify their preferences O’Connor AM. Cochrane Database Syst Rev 2009;Jul 8;(3):CD001431

61.  Provide structured guidance in the steps of decision making and communicating informed values O’Connor AM. Cochrane Database Syst Rev 2009;Jul 8;(3):CD001431

62.  Systematic review (18 randomized trials)  Increase knowledge  Reduce decisional conflict  Decrease testing interest ▪ Relative risk = 0.88 (95% CI, 0.81 - 0.97) Volk RJ. Am J Prev Med 2007;33:428

66.  USPSTF http://www.uspreventiveservicestaskforce.org http://www.uspreventiveservicestaskforce.org  American College of Physicians Guidance Statements http://www.acponline.org/clinical_information/guid elines/guidance/ http://www.acponline.org/clinical_information/guid elines/guidance/

69.  Independent panel of nonfederal experts in prevention and evidence-based medicine  Volunteer members represent primary care disciplines ▪ No substantial financial, intellectual, or other conflicts that would impair the scientific integrity of the work of the Task Force

70.  Rigorous review of existing peer-reviewed evidence  Ratings reflect the strength of the evidence on the harms and benefits of a preventive service ▪ Task Force does not consider the costs of providing the service or make recommendations for coverage

71. GradeEvidenceRecommendation AHigh certainty of substantial net benefitProvide BHigh certainty of moderate net benefit Moderate certainty of moderate/substantial net benefit Provide CModerate certainty that net benefit is smallSelectively offer/provide DNo benefit or harms outweigh benefitsDo not provide IInsufficient evidence regarding balance of benefits and harms

72.  Patient Protection and Affordable Care Act  Requires private insurers and Medicaid to cover preventive services that have a grade of “A” or “B” from the USPSTF  Secretary of HHS can modify Medicare coverage of prevention services to be consistent with USPSTF

73.  Grade A  Cervical cancer  Colorectal cancer  Grade B  Breast cancer  Lung cancer (LDCT)

74.  Grade I  Bladder cancer  Skin cancer  Oral cancer

75.  Grade D  Ovarian cancer  Pancreatic cancer  Prostate cancer  Testicular cancer

76.  Screening programs have important clinical and public health implications  Screening programs should be based on  Burden of suffering  Natural history  Diagnostic tests  Treatments

77.  Screening efficacy is best demonstrated by randomized controlled trials showing  Decreased mortality  Decreased morbidity  Preventing disease (sometimes)

78.  Absolute benefits of screening are small  Most people face only potential harms from screening  Physicians should support patients in making informed decisions about cancer screening

79.  Screening guidelines change   Use USPSTF, ACP to prepare for Boards