Prostate Cancer Screening
2012
Paul L. Crispen, MD
Department of Surgery
University of Kentucky
Conflicts of Interest
• I am a Urologist
• I have a family member who died of
prostate cancer
Critical Questions
• Should all men be screened?
• Who should be offered screening?
• How should men be screened?
Outline
• Purpose of screening
• Method of screening
• Contemporary screening trials
• Current Guidelines
• Questions
Purpose of Screening
• Early detection of potentially lethal
malignancy
• Early treatment will confer advantages
over treatment of clinically detected
malignancy
Purpose of Screening
• Earlier detection of potentially lethal
malignancy
Purpose of Screening
• Early treatment will confer advantages
over treatment of clinically detected
malignancy
Five year survival
Method of Screening
• Digital Rectal Exam
– Subjective
• Serum Prostate Specific Antigen (PSA)
– Not specific
What causes a change in PSA?
•
•
•
•
•
BPH
Prostate Cancer
Prostate inflammation/infection - prostatitis
Medications: e.g. 5-alpha reductase’s, CAM
Other causes:
–
–
–
–
Trauma/Instrumentation (e.g. cystoscopy, biopsy)
Radiation
Ejaculation and DRE (variable, inconsistent)
PSA assay
Prostate Specific Antigen (PSA)
• PSA <4 ng/mL considered “normal”
• PSA 4-10 ng/mL assoc. with 22-30%
positive biopsy rate
• PSA >10 ng/mL assoc. with 66%
positive biopsy rate
Oesterling J, et al. Cancer: Principles & Practice of Oncology. 5th ed. 1997;1322-1386.
Brawer MK. CA Cancer J Clin. 1999;49:264-281.
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%
<0.5
6.6%
12.5%
Thompson et al, JAMA 294:66-70, 2005.
Thompson et al, NEJM 350:2239-46, 2004.
Prostate Cancer Screening Trials
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.
•
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
ERSPC
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%
ERSPC
• Screening  21% reduction in prostatecancer 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.
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, p=0.003.
• 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
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 2012;104:125–132
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.
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.
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
Potential Harm
• Prostate Biopsy:
• Majority are negative
• Bleeding
• Infection
• Prostate Cancer Treatment
• Erectile Dysfunction
• Urinary Symptoms/Incontinence
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
U.S. Guidelines
• American Urological Association
– 40 years old
– > 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
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
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
How does prostate cancer screening
efficacy compare with screening for
other common cancers?
Breast Cancer Screening
• CISNET and STS
• Number needed to screen:
– STS: 465
– CISNET:
• 40-49 years:
• 50-59 years:
• 60-69 years:
• 70-79 years:
746
351
233
377
Tabar et al, Journal of Medical Screening 2004.
Hendrick and Helvie , AJR 2012
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
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…
PLCO
Sub-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), p=0.03.
• Number needed to treat to
prevent one PCa death at
10 years was 5.
Crawford et al, JCO 2011
No Comorbidities
One or more
Comorbidities
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.
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”
Questions
• These are my opinions based on
available data
• Opinions will continue to change as
more data becomes available
Should all men be screened for
Prostate Cancer?
• No
Who should be offered
screening for prostate cancer?
• Life expectancy greater than 10 years
• Patients who request screening
• Patients who understand risks and
benefits
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
Thank You
crispen.paul@uky.edu