Transcript Hoffman Cancer Screening Thursday school 2014

Richard M. Hoffman, MD, MPH
DOIM Thursday School
October 30, 2014
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“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)
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Screening definition
Criteria for implementing screening
Evaluating the efficacy of screening
Critical review of prostate cancer screening
 Evidence
 Guidelines
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USPSTF cancer screening recommendations
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Applying a diagnostic test to asymptomatic
people to classify their likelihood of having a
particular disease
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“Likelihood of disease”
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“Likelihood of disease”
 Persons with abnormal tests require further
diagnostic studies
 Gold standard tests usually invasive, riskier,
and more expensive
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“Asymptomatic”
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“Asymptomatic”
 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)
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“Asymptomatic”
 Target high-risk population
▪ Behaviors
▪ Smoking
▪ Risk factors
▪ Family history
Sporadic (65%–85%)
+ Family
history
(10%–30%)
Rare
syndromes
(<0.1%)
CDC
FAP (1%)
HNPCC (5%)
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“Asymptomatic”
 Older age (> 50 years)
▪ 70+ million
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“Asymptomatic”
 Expensive
▪ Screening
▪ Gold-standard diagnosis
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“Asymptomatic”
 Policy decision
▪ Limited health care resources
▪ Competing demands
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Epidemiology
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Natural history
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Screening tests
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Treatments
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Important clinical problem
 Common
 Substantial burden of suffering
▪ Impairs quality of life
▪ Hospitalizations
▪ Death
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Time course of disease
 Long asymptomatic period to make early
diagnosis
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Acceptable
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Available
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Accurate: valid and reproducible
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Detects clinically important disease
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Acceptable
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Available
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Efficacious
 Reduces disease-specific mortality and
morbidity in randomized controlled trial
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Outcomes
 Decreased disease mortality and morbidity
▪ Decreased incidence of advanced-stage disease
▪ Prevents disease (sometimes)
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Screening study designs
 Randomized controlled trial: least biased
 Observational
▪ Cohort
▪ Case-control
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Selection
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Lead-time
 Overdiagnosis bias
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Length-time
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Healthy volunteer
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Adherent
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Worried well
©2006 UpToDate® • www.uptodate.com
Licensed to University of New Mexico
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Failure to adjust for detecting “pseudodisease”
 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
©2006 UpToDate® • www.uptodate.com
Licensed to University of New Mexico
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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.
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Microscopic cancer (found with PSA testing)
to clinical detection
 5 to 15 year interval
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Prostate-specific antigen (PSA)
 PPV: 30%
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Digital rectal exam
 PPV: 28%
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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
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High burden of disease
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Long asymptomatic stage
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Available screening tests
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Available treatments
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European Randomized Study of Screening for
Prostate Cancer (ERSPC)
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Prostate, Lung, Colorectal, and Ovarian
Cancer Screening Trial (PLCO)
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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
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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
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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
Relative risk = 0.80 (95% CI 0.65 – 0.98)
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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
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Randomization methods, screening
protocols, and biopsy criteria varied across
countries and over time
 Considered a meta-analysis
▪ Positive results only in Netherlands, Sweden
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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
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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
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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
Rate ratio = 1.22 (95% CI, 1.16 - 1.29)
Rate ratio = 1.13 (95% CI, 0.75 - 1.70)
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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)
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American Cancer Society (ACS)
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American College of Physicians (ACP)
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American Urological Association (AUA)
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United States Preventive Services Task Force
(USPTF)
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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
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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
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Don’t ask, don’t tell (unless they ask)
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Complex decisions
 Multiple acceptable options involving
significant tradeoffs among different
possible outcomes
 Extensive effect on the patient
 Controversial
Braddock CH. JAMA 1999; 282:2313
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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
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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/
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PSA screening is controversial
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For most men, chances of harms of screening
outweigh chances benefits
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Most prostate cancers are indolent
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Most men, even if not screened, will not be
diagnosed with or die from prostate cancer
Qaseem A. Ann Intern Med 2013;158:761
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PSA testing increases risk of cancer diagnosis
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PSA does not identify high-risk cancers
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Small potential benefit
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Many potential harms
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Not “just a blood test”
Qaseem A. Ann Intern Med 2013;158:761
Benefits (screening every 1 to 4 y for 10 y)
Men, n
10-year PCa death no screening
5 in 1000
10-year PCa death with screening
4-5 in 1000
Net benefit
0-1 in 1000
Harms (screening every 1 to 4 y for 10 y)
Men, n
False positive test
100-120 in 1000
Prostate cancer diagnosis
110 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
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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
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Tools to support decision making when
evidence is uncertain and/or very sensitive to
patient preferences
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Formats: written, video, interactive computer
programs, Web-based
Rimer BK. Cancer 2004; 101:1214. Barry MJ. Ann Intern Med 2002; 136:127
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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
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Help patients to recognize the valuessensitive nature of the decision and clarify
their preferences
O’Connor AM. Cochrane Database Syst Rev 2009;Jul 8;(3):CD001431
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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
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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
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USPSTF
http://www.uspreventiveservicestaskforce.org
 American College of Physicians Guidance
Statements
http://www.acponline.org/clinical_information/guid
elines/guidance/
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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
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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
Grade Evidence
Recommendation
A
High certainty of substantial net benefit
Provide
B
High certainty of moderate net benefit
Moderate certainty of moderate/substantial net
benefit
Provide
C
Moderate certainty that net benefit is small
Selectively
offer/provide
D
No benefit or harms outweigh benefits
Do not provide
I
Insufficient evidence regarding balance of benefits and harms
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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
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Grade A
 Cervical cancer
 Colorectal cancer
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Grade B
 Breast cancer
 Lung cancer (LDCT)
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Grade I
 Bladder cancer
 Skin cancer
 Oral cancer
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Grade D
 Ovarian cancer
 Pancreatic cancer
 Prostate cancer
 Testicular cancer
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Screening programs have important clinical
and public health implications
Screening programs should be based on
 Burden of suffering
 Natural history
 Diagnostic tests
 Treatments
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Screening efficacy is best demonstrated by
randomized controlled trials showing
 Decreased mortality
 Decreased morbidity
 Preventing disease (sometimes)
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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
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Screening guidelines change 
 Use USPSTF, ACP to prepare for Boards