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Prostate Cancer Screening 2012

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Title: Prostate Cancer Screening 2012


1
Prostate Cancer Screening 2012
Paul L. Crispen, MD Department of
Surgery University of Kentucky
2
Conflicts of Interest
  • I am a Urologist
  • I have a family member who died of prostate cancer

3
Critical Questions
  • Should all men be screened?
  • Who should be offered screening?
  • How should men be screened?

4
Outline
  • Purpose of screening
  • Method of screening
  • Contemporary screening trials
  • Current Guidelines
  • Questions

5
Purpose of Screening
  • Early detection of potentially lethal malignancy
  • Early treatment will confer advantages over
    treatment of clinically detected malignancy

6
Purpose of Screening
  • Earlier detection of potentially lethal
    malignancy

7
Purpose of Screening
  • Early treatment will confer advantages over
    treatment of clinically detected malignancy

Five year survival
8
Method of Screening
  • Digital Rectal Exam
  • Subjective
  • Serum Prostate Specific Antigen (PSA)
  • Not specific

9
What causes a change in PSA?
  • BPH
  • Prostate Cancer
  • Prostate inflammation/infection - prostatitis
  • Medications e.g. 5-alpha reductases, CAM
  • Other causes
  • Trauma/Instrumentation (e.g. cystoscopy, biopsy)
  • Radiation
  • Ejaculation and DRE (variable, inconsistent)
  • PSA assay

10
Prostate Specific Antigen (PSA)
  • PSA lt4 ng/mL considered normal
  • PSA 4-10 ng/mL assoc. with 22-30 positive biopsy
    rate
  • PSA gt10 ng/mL assoc. with 66 positive biopsy rate

Oesterling J, et al. Cancer Principles
Practice of Oncology. 5th ed. 19971322-1386.Braw
er MK. CA Cancer J Clin. 199949264-281.
11
Prostate Cancer in low PSA
PSA level Prevalence of Prostate Cancer High-Grade Disease
3.1 - 4.0 26.9 25.0
2.1 - 3.0 23.9 19.1
1.1 - 2.0 17.0 11.8
0.6 - 1.0 10.1 10.0
lt0.5 6.6 12.5
Thompson et al, JAMA 29466-70, 2005. Thompson et
al, NEJM 3502239-46, 2004.
12
Prostate Cancer Screening Trials
13
NY Times Health Section 2011
U.S. Panel Says No to Prostate Screening for
Healthy Men By GARDINER HARRIS Published October
6, 2011 Healthy men should no longer receive a
P.S.A. blood test to screen for prostate cancer
because the test does not save lives over all and
often leads to more tests and treatments that
needlessly cause pain, impotence and incontinence
in many, a key government health panel has
decided.
14
  • Screening reduced rate of prostate cancer death
    by 20 (with associated overdiagnosis risk)
  • 1410 pts needed to be screened, 48 treated to
    prevent one death

Schroder et al, NEJM 360 1320-8, 2009
15
ERSPC
16
ERSPC
  • 162,243 men randomized
  • Screening q 2-4 years vs. usual care
  • Compliance in screening group 82
  • Screening in the control group ??
  • 11 years of follow up (median)
  • Detection was higher in screening group
  • 6963 cases vs. 5396, or cumulative incidence of
    9.6 vs. 6.0

17
ERSPC
  • Screening ? 21 reduction in prostate-cancer
    death
  • Number needed to screen 1055
  • Number needed to treat 37

Up to 29 reduction if corrected for
noncompliance in the screening arm and
contamination of the control arm.
18
At 11 years, 299 prostate-cancer deaths in
screening group and 462 in the control group.
Rate ratio 0.79, 95 confidence interval
0.68-0.91, p0.003.
19
  • Caveats
  • 1. 52 contamination in control group
  • -Cancers in control group were stage I
    and II
  • 2. Limited follow-up
  • 3. Substantial proportion pre-screened (44)

Andriole et al, NEJM 360 1310-9, 2009
20
(No Transcript)
21
PLCO
  • 76,693 men in the US randomized, 1993-2001
  • Annual screening vs. usual care
  • Compliance in screening group 86
  • Screening in the control group 52
  • 13 years of follow-up (median)
  • Complications of screening
  • PSA and DRE minimal
  • Biopsy 68 per 10,000 infection, bleeding,
    retention

Andriole et al. J Natl Cancer Inst
2012104125132
22
Number of Cases Identified
More cancers identified in the screening group
(4250 vs. 3815). Rate ratio 1.12, 95 confidence
interval 1.07-1.17.
23
Number of Prostate Cancer Deaths
At 13 years, 158 prostate-cancer deaths in
screening group and 145 in the control group.
Rate ratio 1.09, 95 confidence interval
0.87-1.36.
24
Why do PLCO and ERSPC have different results?
  • Contamination in the non-screening arm
  • 50 in PLCO, and negligible in Europe
  • Location of treatment
  • Type of treatment

25
Potential Harm
  • Prostate Biopsy
  • Majority are negative
  • Bleeding
  • Infection
  • Prostate Cancer Treatment
  • Erectile Dysfunction
  • Urinary Symptoms/Incontinence

26
Potential Harm
  • Potential harms For every one life saved
  • Between 300 and 1000 men have to undergo
    screening
  • Between 10 and 40 men have to undergo treatment
  • Indiscriminate treatment of low-risk disease
  • Estimates indicate over one million extra men
    have undergone treatment in the US due to PSA
    screening to save at most 56,000 lives

Albersten JNCI 2009
27
U.S. Guidelines
  • American Urological Association
  • 40 years old
  • gt 10 year life expectancy
  • Informed consent
  • PSA and DRE
  • American Cancer Society
  • 50 years old (45 with increased risk)
  • Informed consent
  • PSA with or without DRE

28
U.S. Guidelines
  • American College of Physicians
  • Patient counseling
  • NCCN
  • Patient counseling beginning at age 40
  • American Academy of Family Practitioners
  • Recommends against screening
  • US Preventive Services Task Force
  • Recommends against screening

29
International Guidelines
  • European Association of Urology
  • Against national screening
  • UK and NZ
  • Case by case basis following patient counseling
  • Japanese Urological Association
  • Baseline PSA at 40 years
  • Annual at 50 years
  • No upper age limit for screening

30
How does prostate cancer screening efficacy
compare with screening for other common cancers?
31
Breast Cancer Screening
  • CISNET and STS
  • Number needed to screen
  • STS 465
  • CISNET
  • 40-49 years 746
  • 50-59 years 351
  • 60-69 years 233
  • 70-79 years 377

Tabar et al, Journal of Medical Screening
2004. Hendrick and Helvie , AJR 2012
32
Colon Cancer Screening
  • PCLO
  • Flexible sigmoidoscopy
  • Relative risk reduction 12 years
  • Incidence 21
  • Cancer specific death 26
  • Number needed to screen 871

Schoen et al. NEJM 2012
33
Screening for Prostate Cancer Comparison with
Other Cancers
  • Possible risk reduction
  • Greater number need to screen
  • Recent study suggest that appropriately targeted
    screening may improve these figures substantially
    for prostate cancer

34
PLCOSub-set Analysis of Healthy Men
  • Sub-set analysis of men with no comorbidities
    (that predict cardiovascular or cancer mortality)
  • Adjusted hazard ratio for screening group vs.
    unscreened group was 0.56 (0.33-0.95), p0.03.
  • Number needed to treat to prevent one PCa death
    at 10 years was 5.

No Comorbidities
One or more Comorbidities
Crawford et al, JCO 2011
35
Summary of Randomized Trial Data on Screening
  • PLCO
  • No benefit of screening
  • Flawed due to contamination of the control arm
  • ERSPC
  • 21 relative risk reduction
  • 1055 needed to screen 37 needed to treat
  • Screening may be beneficial
  • In younger, healthier men
  • As follow up lengthens
  • Targeted screening reduces NNS to 300 and NNT to
    10 or 12.

36
Screening Summary
  • There are potential benefits
  • Potential prostate-cancer specific survival
    benefit in appropriate populations
  • More likely to benefit younger, healthier
    patients
  • There are potential harms
  • False-positive test leading to other tests
  • Detection of indolent prostate cancer leading to
    unnecessary treatment and treatment related side
    effects
  • Screening decisions must
  • Balance potential benefits and potential harms
  • Involve the patient shared decision-making

37
Questions
  • These are my opinions based on available data
  • Opinions will continue to change as more data
    becomes available

38
Should all men be screened for Prostate Cancer?
  • No

39
Who should be offered screening for prostate
cancer?
  • Life expectancy greater than 10 years
  • Patients who request screening
  • Patients who understand risks and benefits

40
How should men be screened for prostate cancer?
  • PSA and DRE
  • Starting at age 40-50
  • Ending at age 70-75
  • Interval of screening
  • Depends on PSA and risk factors

41
Thank Youcrispen.paul_at_uky.edu
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