Download Prostate Cancer Screening

SCREENING FOR
PROSTATE CANCER
EVIDENCE AND DEBATE
LEARNING TOPICS
• Part A: Show me the numbers!
• What does the available evidence show about the benefits
and harms of prostate cancer screening?
• What additional data may be added to a PSA test to help
guide management of an elevated PSA test?
• Part B: So what do we do? Discuss!
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Should we be screening for prostate cancer?
If so, PSA or DRE or both?
Who should we consider screening? How often?
Should it be a decision that is shared between providers
and patients? How do we do that?
THIS IS ON THE BOARDS TOO!
• A 52-year-old man is evaluated during a periodic health
examination. He has benign prostatic hyperplasia, and his
father died of prostate cancer at the age of 74 years. His
only current medication is tamsulosin. He has no urinary
symptoms. Vital signs are normal, as is the remainder of
the physical examination
• Which of the following is the most appropriate
management?
A. Discuss the risks and benefits of prostate cancer screening
B. Obtain a prostate-specific antigen level
C. Perform a digital rectal examination
D. Perform a digital rectal examination and obtain a prostatespecific antigen level
BACKGROUND
• Prostate cancer is prevalent
• 1 man in 6 diagnosed in his lifetime
• Autopsy studies of men who died of other causes found
prostate cancer in 30% of men under 80, and in 80% of men
over 80
• Most men die with, not from, prostate cancer
• Second leading cause of cancer death in men after lung
• 1 man in 36 will die from prostate cancer
• Prostate cancer deaths have been falling for 20
years
• 40% reduction in prostate ca mortality 1993-2009
• PSA screening was approved by the FDA in 1994
PSA TEST CHARACTERISTICS
PSA >4.0
Sensitivity 21% for all prostate ca
• 51% for high grade prostate ca (gleason >8)
Specificity 91%
• False elevation in:
• BPH, prostatitis
PSA >3.0
Sensitivity 32% (68% high grade)
Specificity 85%
TWO LARGE RCTS: METHODS
PLCO: 10 U.S. centers
 76,685 Men 55-74
 13 years f/u
 Exclusion: Hx of prostate
Ca, current cancer Tx,
>1 PSA screening prior
to entry
 Annual PSA and DRE vs.
usual care
 PSA cutoff 4 ng/mL
ERSPC: multiple countries
162,388 men 55-69
11 years f/u
Exclusion: Hx of prostate
Ca
 Q4 years PSA vs. usual
care.
Sweden: every 2 years. Belgium +
Netherlands, also DRE
 PSA cutoff 3 ng/mL
Finland: 4 ng/mL Belgium: 10ng/mL up
to ‘97
ADHERENCE AND
CONTAMINATION: PLCO ISSUES
PLCO
• Compliance 85% for PSA
screening, 86% DRE
• 52% rate of PSA testing
control group in 6th year
• 41-46% rate of DRE testing
control grp
• 44% of subjects in each
group had 1 or more PSA
at baseline
ERSPC
• Compliance 82%
(screened at least
once)
• 20% rate of PSA testing
control grp
ESRPC BENEFIT?
CRUNCH THE NUMBERS
Death from Prostate Ca 0.4% vs. 0.5% (p=0.003)
• RRR?
• 20%
• ARR?
• 0.1%
• Number needed to invite?
• 1000
• (down from 1410 at 9 years)
No difference in all-cause mortality
GOTEBERG/SWEDISH TRIAL
• 50% of subjects also included in ERSPC
• 20,000 men 50-65
• Intervention PSA q 2 years
• 14 year f/u
• ARR 0.9% to 0.5%: NNI ~300
• 12.7% cases of prostate cancer in
intervention vs. 8.2%
ESRPC HARM?
How many men were overdiagnosed?
->Diagnosed by screening that would not have been
diagnosed before death
ESRPC: Number Needed to Diagnose to prevent one
death: 33
Cases of prostate Ca: 65% higher risk with screening
9.6% vs. 6.0%
Low risk prostate ca
60% vs. 42% of cases
False positives? (risk of biopsy?)
16% of 136,000 PSA tests were positive -> 85% of
these
underwent bx
->21,000 biopsies for 13,000 cases diagnosed
AFTER THE BIOPSY:
ASSIGNING RISK
• TNM staging (T4 =invading adjacent tissue)
• Gleason Score: histology
• Sum of the most common cell pattern and
the highest grade
TREATMENT FOR PROSTATE CANCER:
WHAT ARE THE AES?
• If localized and life expectancy >10 yrs and
intermediate risk (gleason >7, PSA >10)
• Radical prostatectomy and radiation equally effective
• Impotence and Incontinence are common
complications of radical prostatectomy
• Radiation proctitis and cystitis common
• If high-risk
• Androgen deprivation tx (gnRH agonist)
• AES:impotence, hot flashes, fatigue, gynecomastia,
osteoporosis, weight gain
• Chemotherapy may increase survival 3-6 months in metastatic
disease: docetaxel
TREATMENT VS. WATCHFUL WAITING
FOR LOCALIZED PROSTATE CANCER
US PIVOT RCT
• T1-T2, any grade, PSA
<50
• Most PCa detected
through screening
• No significant
difference in mortality
• 50% of participants
died by the end of
the 10 year trial
Scandinavian Study
• T1-T2, any grade, PSA
<50
• Most PCa detected
through sx (> 75%
palpable)
• 6% absolute reduction
in mortality at 15 years
with treatment
• 20.7% vs.14.6%
• No benefit in men older
than 65
OTHER CONSIDERATIONS
• Lead Time estimated to be 6 or 7 years
• Why is this important?
BEFORE THE BIOPSY:
HOW CAN WE MAKE A SCREENING TEST
BETTER? RISK STRATIFICATION
• DRE?
• Doubling time of PSA?
• PSA density (relative to prostate size)
• PCA3 is a new tumor marker, studies
underway
• Higher specificity/sensitivity for high risk ca
• May be most useful in determining watchful waiting
vs. treatment?
MORE INDIVIDUALIZED RISK
• African American Race: ~40% increased risk
based on prostate cancer prevention trial
SWEDISH STUDY CASE CONTROL
• Subgroup of ERSPC
• April 2013: Case Control study of relation
between PSA at age 40-55 and risk of metastasis
• 15-year risk for metastatic prostate ca at highest
deciles of PSA:
• 0.6% PSA >1.3 at 40
• 1.6% >1.6 at 45-49
• 5.2% >2.4 at 51-55
• 25-year risk is 0.2% for a 60 yr old man if PSA <1
• If <1.0 at 45-> 2 repeat screenings in 50s and at
60?
WHAT IS AN INTERNIST TO DO?
• To screen or not to screen? What would you do?
Discuss NEJM case
• IF we screen:
• What value should we consider elevated?
• What ages should we screen?
• Men 50-65 with life expectancy >10-15 years?
• Start at 45 like swedish study authors suggest?
• With DRE?
• How often?
• Every 4 years? Every 2? Less often if initial <1?
• Shared decision?
• What are the barriers to this?
THIS IS ON THE BOARDS TOO!
• A 52-year-old man is evaluated during a periodic health
examination. He has benign prostatic hyperplasia, and his
father died of prostate cancer at the age of 74 years. His
only current medication is tamsulosin. He has no urinary
symptoms. Vital signs are normal, as is the remainder of
the physical examination
• Which of the following is the most appropriate
management?
A. Discuss the risks and benefits of prostate cancer screening
B. Obtain a prostate-specific antigen level
C. Perform a digital rectal examination
D. Perform a digital rectal examination and obtain a prostatespecific antigen level
SHARED DECISION MAKING
• IOM statement 2001: patient-centered care
ensures “that patient values guide all clinical
decisions.”
• An intervention should be considered a standard
when there is “virtual unanimity among patients
about the overall desirability… of the outcomes.”
David Eddy
• In SDM patients and providers discuss the risks,
benefits, and burdens of medical tests and
interventions with the goal of reaching decisions
that are concordant with a patient’s goals and
values
HOW DO WE HAVE SHARED DECISIONS
IN THE OFFICE?
• ASK: invite to participate, Assess for knowledge
• “Tell me what you know about ….”
• TELL:
• Communicating statistics on risks and benefits of screening
• Teach-back
• ASK: what matters to them? What questions to they
have? What decision sounds right for them?
• Doing everything possible to avoid dying from prostate
cancer?
• Keeping sexual and urinary function? Avoiding a biopsy?
“BUT IT’S JUST A BLOOD TEST, DOC!”
HOW DO WE COMMUNICATE
STATISTICS TO PATIENTS?
DECISION AIDS
• Studies show that when patients are more informed
they are more likely to take an active role in
medical decision making
• Meta-analysis of Prostate Cancer screening
decision aids
• Increase patient knowledge
• increase patient participation in decision making
• lower PSA testing
• Most are involved (DVDs, long pamphlets), tested
under ideal circumstances -> implementation is
challenging
TRY THIS
Stats review:
• 1/6 is diagnosed in his lifetime, 1/36 will die
• Screening increases risk of diagnosis of prostate
cancer from 6/100 to 10/100
• NNI: 1000
• NND: 33
• Most of these men will still be treated
• (field is evolving with PCA3, PSA density, doubling time,
treatment vs. watchful waiting, etc.)