Transcript Broghammer - PCA Screening4.10.14x

Preventative Care and
Monitoring for Prostate Disease
Joshua Broghammer, MD FACS
Assistant Professor, Dept of Urology
University of Kansas Medical Center
Disclosures
• I am not a urologic oncologist
• Reconstructive urologist
• Inherent bias against over treatment
Objectives
• Incidence of prostate cancer
• Screening guidelines
• Screening controversies
Incidence of Prostate Cancer
• 20101
– 196,038 men diagnosed with PCA
– 28,560 died of PCA
• Excluding skin cancer, most common cancer
among men
• Second leading cancer killer in men
1CDC
website http://www.cdc.gov/cancer/prostate/statistics/
Prostate Cancer
• Since 1992, an annual decline in prostate
cancer mortality of 4% per year has been
observed
– Compared with decrease in breast cancer
mortality of approximately 2.7%, and colorectal of
4.7% (since 2002), and lung of 2%
Figure 4. Trends in age-standardized death rates (log scale) for major cancers by age, 1970–2006.
Jemal A, Ward E, Thun M (2010) Declining Death Rates Reflect Progress against Cancer. PLoS ONE 5(3): e9584.
doi:10.1371/journal.pone.0009584
http://www.plosone.org/article/info:doi/10.1371/journal.pone.0009584
Prostate Cancer Screening
Screening-Digital Rectal Exam
• Detects 25% of cancers we detect today
• Abnormal in 6-15% of men
• May be the only sign of aggressive cancer2
2. Okotie et al., Urology. 2007 Dec;70(6):1117-20.
Prostate Anatomy
http://besthealth.bmj.com
Tropicana
PSA
• Prostate specific antigen
• Serine Protease (kallikrein like)
– Semenogelin I and II
• Normal component of ejaculate
• FDA approved WITH DRE
– Widespread use in 1988
Factors Affecting PSA Level-Size
Matters
Other Factors
• UTI
• Prostate surgery
• Other instrumentation (foley, etc)
• Prostate inflammation
– Do not treat with antibiotics and repeat
– Consider rescreen in 3 months
Non-factors
• Sexual intercourse
• Digital rectal examination
Results of Cost Analysis of Screening
Intervention
Liver transplantation
Screening mammography (< age 50)
Worst case—CaP Screening
CABG—2 vessel/angina
Captopril for hypertension
Hydrochlorathiazide for hypertension
Best case—CaP Screening
Stop smoking MD message
Cost per
QALY Gained
$237,000
$232,000
$145,600
$106,000
$ 82,600
$ 23,500
$ 8,700
$ 1,300
QALY=quality-adjusted life years; CaP=prostate cancer; CABG=coronary artery bypass graft
Thompson IM, Optenberg SA. Oncology (Huntingt). 1995;9:141-145.
Screening
• PSA 0-4 ng/mL classically was the normal range
– Some historical evidence supports lowering limit to 0-2.5
• Estimated that this would double the number of men age 40-69
with an abnormal result.3
• PSA velocity
– Defined as >.75ng/ml year
• Age specific PSA
Age
(years)
40–49
50–59
60–69
70–79
Recommended Reference
Range for Serum PSA (ng/mL)
0.0–2.5
0.0–3.5
0.0–4.5
0.0–6.5
3. Smith DS et al,. J Urol. 1998 Nov;160(5):1734-8.
Screening
• PSA density- PSA/volume of prostate
– 0.15 ng/mL/cm3
– Prostate cancer cells produce 10x more PSA
• Free PSA
– Ratio of free to total PSA is reduced in prostate
cancer
– 25%
Screening Controversies
• Economic benefits
– How much screening is needed to save 1 life?
• 503 to save one life (updated from ERSPC trial)
• Quality of Life
– Do risks outweigh benefits
• Risks associated with the test
Loeb S et al., J Clin Oncol. 2011 Feb 1;29(4):464-7
Screening Pros
• 90% of prostate cancers detected are localized
to the prostate (potentially curable)
• PSA of 4.0 ng/ml has good sensitivity
– Detects over 90% of aggressive prostate cancers
– 56% of non-aggressive cancers
Screening Cons
• Screening tests must satisfy the following:
– Detect curable disease
– Provide survival advantage
– Treatment options which work
• Evidence is lacking to support a survival
advantage, despite mortality decrease
Risk of a Biopsy
• Hospitalization rates of 0.6-4.1%
– 0.3% death rate 30 days after (70% lower than aged
matched controls)
• Era of quinolone resistance
• Ecoli-15% resistance rate in community
• High risk if your patient has gotten abx in 1 year
Nam RK et al. J Urol 2010
PLCO Cancer Screening Trial
• Effects of cancer screening on men 55-74
– Excluded if PSA screening in last 3 years
• Screening completed 2006
• Data collection until 2015
• 76,685 enrolled
– Intervention arm (38,340)
• Annual PSA x 6 years, DRE x 4 years
– Control arm (38,345)
• Usual care-including opportunistic screening
PLCO 2012 Results
• Follow up
– 92% at 10 years
– 57% at 13 years
• 4250 vs. 3815 diagnosed with PCA
– 12% increase in intervention arm
• Mortality rates from PCA
– 3.7 vs. 3.4 per 10K person years (no difference)
Andriole GL et al, J Natl Cancer Inst. 2012 Jan 18;104(2):125-32.
PLCO Controversy
• Control arm had many men screened
• PSA cutoff of 4.0 may be too high
• Selection bias-eligible men may be excluded
due to prior screening
European Randomized Study of
Screening for Prostate Cancer Trial
• Effects of PCA screening on those 50-74
• 182,000 enrolled
– Intervention arm
• Screening 1 every 4 years
– Control Arm
• No screening
• PSA cutoff was 3.0 ng/mL
• Primary outcome-death from prostate cancer
Schroder FH et al., N Engl J Med. 2009 Mar 26;360(13):1320-8
ERSPC Results
• Incidence of PCA
– 8.2% vs. 4.8%
• Rate ratio for death from PCA 0.80
• PSA reduced death rate by 20%, but high over
diagnosis rate
– 1410 needed to screened, 48 needed to treat at 9 yrs
– 503 needed to screened, 18 needed to treat at 12 yrs
ERSPC Controversy
• Shorter follow up
• Modest benefit in screening
• Several different countries (7 centers)
– Sweden and Netherlands significant PCA mortality
– Other five centers showed no difference
To Screen or Not to Screen
• Need to treat 18-48 men to save a life
– What if you’re “that guy”
• Many studies have significant flaws
– Cross over of non-screened control groups
• Quality of life is an important factor not
considered
– Treatment
– Death of PCA
Screening Guidelines
• No screening
– US Preventative Services Task Force (Grade D)
• Chairman was a pediatrician
– American Academy of Family Practice
• Selected screening
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American Urological Association
American Cancer Society
National Cancer Institute
American College of Physicians
AUA Guidelines
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No PSA Screening <40
No routine screening in average risk age 40-55
Individualized screening for high risk or AA <55
55-69: Shared decision making process
– Screening interval of 2 years or more
• No screening in men 70+ with life expectancy
of <10-15 years.
Urinary Symptoms-LUTS
• Obstructive:
– Decreased force
– Hesitancy
– Intermittency
– Incomplete emptying
• Irritative:
– Frequency
– Urgency
Urinary Symptoms
• Many things can be a cause
• Including prostate cancer
• Talk to your patients
Screening Guidelines
No Organization
Supports Annual PSA
Screenings in Average
Risk Males
Where did we go wrong?
• Dialing down PSA
• Screening everyone
• Lack of leadership
• Inherent biases
Treatment Biases
1. Cure cancer
2. Prevent incontinence
3. Prevent erectile dysfunction
Treatment Modalities
• Watchful waiting
• Active Surveillance
• Seed Implants
• External radiation
• Radical Prostatectomy
Watchful Waiting
• Repeated PSA testing
• Intervention at a predetermined PSA level
• No real set guidelines
• Doesn’t sit well with patients
Active Surveillance
• T1 disease (biopsy +, negative on DRE)
• Gleason 6 (low grade disease)
• ≤ 2 out of 6+ cores positive
• PSA <10
• No cores with >50% involvement
Active Surveillance
• Annual repeat biopsy
– Combats sampling error
• Annual PSA
– Doubling time of <2 years
• Consideration for MRI
– Evaluate for missed tumors
Prostate Cancer Prevention
• PCPT-Prostate cancer prevention trial
– Finasteride (Proscar)
– 10% reduction in prostate cancer
• 10.5% finasteride group vs 14.9% in placebo
– Increase in high grade prostate cancer
• 6.4% finasteride group vs 5.1% in placebo
• Not FDA approved for the prevention of PCA
Prostate Cancer Prevention
• SELECT-Selenium and Vitamin E Cancer Prevetion
Trial
• Alone and in combination
• Selenium- Trend toward but not significant for
DM
• Vitamin E-17% more cancers
– 11 per 1000 men
Conclusions
Conclusions
• PSA testing should exist in some form.
• Informed decision.
• Continued screening for high risk men.
Questions?
44