1. health and fitness
2. disease
3. cancer

The Prostate
Cancer Screening
Controversy
Daniel J. Ricchiuti, M.D.
St. Elizabeth Health Center
Primary Care Update
May 18, 2012
Overview
 Background Prostate Cancer and PSA
 Explore the controversy surrounding
prostate cancer screening
 Present current data from randomized
studies
 Discuss practical uses of PSA and
prostate cancer screening in practice
Question #1
 If you are or were a male >50
years of age, would you check a
PSA on yourself?
 NO
 YES
 UNSURE
Question #2
 Do you believe that prostate cancer
screening effects your patients’ overall
mortality?
 NO
 YES
 UNSURE
Question #3
 Do you believe that most of
your patients desire to be
screened for prostate cancer?
 NO
 YES
 UNSURE
Prostate Cancer
Assumptions
 Most common non-cutaneous cancer in
males in U.S.
 Second leading cause of male cancer
mortality
 >28,000 deaths expected in 2012
 Natural history is heterogeneous and not
clearly or consistently understood
Gleason Scoring System
 Glandular architecture
 First number – most common pattern
 ex. 3
 Second number – second most common
pattern
 ex. 4
 Gleason Sum – total of the two
 3+4=7
 Higher the sum the more aggressive the
cancer
Miscellaneous Information
 PCPT:
 Finasteride – 25% reduction in PCA diagnosis
 Those with PCA had more aggressive form
 5 alpha-reductase inhibitors:
 50% reduction in PSA value after 3 months
 SELECT Trial:
 Vitamin E – 17% more cases of PCA in those taking
regularly
Controversies Surrounding
Prostate Cancer




Does screening work?
Is PSA a good screening test?
Does early detection even matter?
Does prostate cancer even need to be
treated?
Prostate Cancer
Treatment Assumptions
 Surgery:
 Removes entire prostate gland
 Risk of incontinence, impotence, major
complications
 Less invasive with robotic approach
Prostate Cancer
Treatment Options
 Radiation:
 More and more precise
 Destroys most of prostate
 Risk of impotence, burns, collateral damage
to bladder, urethra, rectum
 External beam or brachytherapy
 Cryotherapy
 HIFU
Prostate Cancer Risk
Stratification
 Moderate to High Risk:
 PSA ≥ 10
 Gleason Score ≥ 7
 Low Risk:
 PSA < 10
 Gleason Score ≤ 6
Prostate Cancer Risk
Stratification
 Potentially Insignificant Cancer:
 <5% of 1 needle core involved
 Gleason 6 or less
 Low tumor volume
Prostate Specific Antigen
(PSA)
 Glycoprotein produced by epithelial cells of prostate
 Disruption of normal prostate architecture allows
increased amounts into circulation:




BPH
Cancer
Inflammation / infection
Trauma
 Introduction in 1986 dramatically changed medical
practice in U.S.
PSA Interpretation
 No such things as
“normal” PSA
 PSA is age and race
dependent
Age
Caucasian
African
American
40
2.5
2.0
50
4.0
2.5
60
6.0
4.0
70
6.5
6.5
PSA As a Screening Test
 Responsible for profound stage migration
toward earlier stages at diagnosis
 Advanced disease at presentation:
 1988 = 19.2%
 1998 = 4.4%
 Leads to overdetection and overtreatment
of some patients
PSA As a Screening Test
 Despite decrease in risk and stage of
cancer at diagnosis, 90% of men choose
some type of intervention when diagnosed
To Biopsy or Not to Biopsy?
 Elevated PSA has been shown to affect
patients mentally and physically even if the
patient chooses not to have biopsy
 4% risk of sepsis or bleeding with biopsy
 Importance of PSA Kinetics:
 PSA Velocity
 PSA Density
 PSA Doubling Time
 Individualized decision made with guidance
from physician
USPSTF on PCA Screening
Population
Recommendation
Men Younger than Age 75 Years
No recommendation
Grade: I (Insufficient Evidence)
Men Age 75 Years or Older
Do not screen
Grade: D
Risk Assessment
Prostate cancer is more common in older men, African Americans, and men with a family history of prostate cancer.
The same uncertainties about the effects of screening that apply to other men also apply to these higher-risk men.
Screening Tests
The prostate-specific antigen (PSA) test is more sensitive than the digital rectal examination (DRE). The
conventional PSA test cut-point of 4.0 g/L misses some early cancer. However, lowering the cut-point would increase
the rate of false-positive results. Variations of PSA screening have not yet been demonstrated to improve health
outcomes.
Screening Intervals
If PSA screening reduces mortality, screening every 4 years may be as beneficial as annual screening.
Interventions
Management strategies for localized prostate cancer include watchful waiting, active surveillance, surgery, and
radiation therapy.
There is no consensus regarding optimal treatment.
Balance of harms and benefits
•The harms of screening include the discomfort of prostate biopsy and the psychological harm of false-positive test
results.
•Harms of treatment include erectile dysfunction, urinary incontinence, bowel dysfunction, and death. A proportion of
those treated, and possibly harmed, would never have developed cancer symptoms during their lifetime.
For men younger than age 75 years, evidence is
inadequate to determine whether screening improves
health outcomes.
Therefore, the balance of harms and benefits cannot be
determined.
Suggestions for practice
For men age 75 years or older and for those whose life
expectancy is 10 years or fewer, the incremental benefit
from treatment of prostate cancer detected by screening
is small to none.
Therefore, harms outweigh benefits.
Clinicians should discuss the potential benefits and known harms of PSA screening with their patients younger than
age 75 years. Men in this age group should be informed of the gaps in the evidence, and their personal preferences
should guide the decision of whether to order the test.
USPSTF on PCA Screening
 A.U.A. Response:
 concern that recommendations will do more
harm than good
 PSA does provide important information for
diagnosis and risk assessment
 not all patients with PCA require treatment
 until there is a better test, USPSTF is doing
a great disservice to men worldwide
American Academy of
Family Physicians
 2008
 “…insufficient evidence on which to make
a recommendation for or against routine
screening for prostate cancer using
prostate specific antigen (PSA) testing or
digital rectal examination (DRE)”
 Recommends against screening over
age of 75
American College of
Physicians
 No practice guidelines
 Mention of PSA controversy
 Referral to U.S. Preventative Services
Task Force recommendations
American Urological
Association
 Revised Best Practice Policy in
2009 stating:
 …“early prostate cancer testing
(PSA / DRE) should be offered to
well-informed men, 40 years or older
who have a life expectancy of at
least 10 years.”
American Urological
Association
 Revised Best Practice Policy in
2009 stating (cont.):
 The decision to biopsy should be
individualized based on PSA, DRE,
age, race, comorbidities
 Not all prostate cancers require
treatment and not all are fatal
American Cancer Society
 “The ACS does not support routine testing for
prostate cancer of this time”
 Health care professionals should discuss R&Bs
of early prostate cancer detection and offer
testing
 Start discussion at 50 unless increased risk for
prostate cancer
 Men with < 10 year life expectancy should not
be screened
National Cancer Institute
 NCI does not have a recommendation
about prostate cancer screening
 Referral to U.S. Preventive Services
Task Force recommendations
National Comprehensive
Cancer Network (NCCN)
 Excellent discussion re: pros and cons
for screening
 Baseline PSA and DRE is useful
 Careful examination of individual risk
factors in considering biopsy
March 26, 2009 NEJM
 Publication of the only 2 randomized
trials concerning Prostate Cancer
Screening:
 European Randomized Study of
Screening for Prostate Cancer (ERSPC)
 Prostate, Lung, Colorectal, and Ovarian
(PLCO)
 Both studies are ongoing
European Randomized Study
of Screening for Prostate
Cancer (ERSPC)
 162,243 men enrolled from 7 countries
 9 year follow-up
 Screening group:
 various screening approaches
 Averaged PSA every 4 years
 Control group – no formal screening
European Randomized Study
of Screening for Prostate
Cancer (ERSPC)
 20% relative reduction in Prostate
Cancer death with screening
 1410 men would have to be screened
and 48 treated to prevent 1 death from
prostate cancer
European Randomized Study
of Screening for Prostate
Cancer (ERSPC)
 Criticisms:
 Sextant biopsies were used
 Various criteria for biopsy used at different
centers
 Different screening tools used at each center
PSA vs. DRE
Prostate, Lung, Colorectal,
and Ovarian Trial (PLCO)
76,693 men enrolled – all from U.S.
10 study centers
7 – 10 years follow-up
Screening Group – offered annual PSA
for 6 years and annual DRE for 4 years
 Control Group – offered “usual care”




Prostate, Lung, Colorectal,
and Ovarian Trial (PLCO)
 Incidence of death from prostate cancer
was the same in screening and control
groups (2.0 vs. 1.7 deaths per 10,000
person years)
Prostate, Lung, Colorectal,
and Ovarian Trial (PLCO)
 Criticism:
 “PSA contamination” – about half of the
subjects in the control had PSA testing by
year 5
 Control group not true control
Anecdotal Patient
Histories






53 yo WM
Strong family history of prostate cancer
PSA 1.2. Normal DRE
Gleason 6 found on biopsy
Treated with surgery
Recurrent disease
Anecdotal Patient
Histories






65 yo AAM
Longevity in family. Pt. very good health
PSA 6.0. Normal DRE
Prostate biopsy negative
PSA rises at rate of 0.75 / year
4 prostate biopsies – all negative, sepsis
and admission after 2nd biopsy
Anecdotal Patient
Histories





45 yo WM with back pain
No family history of prostate cancer
PSA 250. Bilateral firm on DRE
Prostate biopsy – Gleason 5 + 4 = 9
Bone scan / CT Scan widespread
metastatic disease
 Died 6 months after diagnosis
Anecdotal Patient
Histories






84 yo WM – very healthy
PSA 12. Enlarged prostate on DRE
Biopsy or no biopsy?
Gleason 4 + 4 = 8
Treatment vs. observation
Died of prostate cancer at 86
Question #4
 If you are or were a male >50 years of
age, would you check a PSA on
yourself?
 NO
 YES
 UNSURE
Question #5
 Do you believe that prostate cancer
screening effects your patients’ overall
mortality?
 NO
 YES
 UNSURE