E V I D E N C E A N D D E B AT E

SCREENING FOR PROSTATE CANCER

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!• 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 screeningB. Obtain a prostate-specific antigen levelC. Perform a digital rectal examinationD. Perform a digital rectal examination and obtain a prostate-specific 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 countries162,388 men 55-6911 years f/uExclusion: 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 deathESRPC: 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 casesFalse 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 screeningB. Obtain a prostate-specific antigen levelC. Perform a digital rectal examinationD. Perform a digital rectal examination and obtain a prostate-specific 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.)