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Prostate Specific Antigen
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Prostate Specific Antigen
, PSA, Prostate Cancer Prevention, Prostate Cancer Screening
See Also
Prostate Cancer
Free PSA
Efficacy
PSA
USPSTF Strength of Recommendation
: D
Test Sensitivity
Overall: 79-82% (72% for a PSA >4 ng/ml)
Cancers >1 cm: 90%
More sensitive than
Digital Rectal Exam
(30% for 1 cm tumor)
Much more sensitive than
Acid Phosphatase
Test Specificity
Overall: 59% (93% for a PSA >4 ng/ml)
Positive Predictive Value
: 25% (for PSA>4 ng/ml)
False Positive Rate
: 70% (for PSA >4 ng/ml)
Benign Prostatic Hyperplasia
often increases PSA
Outcomes uncertain despite effective screening
Screening does not decrease overall or
Prostate Cancer
specific mortality
Ilic (2013) Cochrane Database Syst Rev 1:CD004720 [PubMed]
Detection may not impact morbidity
May actually increase morbidity due to
Prostate Cancer
treatment complications
Absolute Risk Reduction
: 1.28 deaths per 1,000 men screened for
Prostate Cancer
To prevent one death from
Prostate Cancer
Number Needed to Screen
: 781
Number Needed to Treat
: 27
References
Schroder (2014) Lancet 384(9959): 2027-35 [PubMed]
Additional tests that improve PSA efficacy
See Elevated PSA management below (includes MRI, biomarkers)
Free PSA
to Total PSA ratio
Normal range varies by age, but ratio <25% is higher risk
Rate of PSA change
Consider referral for higher rate of change, even if <4 ng/ml
Causes
Elevated PSA
Prostate Cancer
Benign Prostatic Hyperplasia
(BPH)
Prostatitis
Prostate
inflammation,
Trauma
, or manipulation
Prostatic infarction
Recent sexual activity
Urologic procedures
Cyst
oscopy
Urinary Catheterization
Screening
Recommendations
Most organizations can not recommend for or against screening based on lack of evidence
See Efficacy above
US Preventive Task Force
American College of Physicians
American Society of Internal Medicine
National Cancer Institute
Centers for Disease Control and Prevention (CDC)
American Academy of Family Physicians
American College of Preventive Medicine
Organizations that advocate
Shared Decision Making
for men ages 55 to 69 years old, but not routine screening
American Cancer Society
Smith (2013) CA Canc J Clin 63(2): 88-105 [PubMed]
American Urological Association
https://www.auanet.org/common/pdf/education/clinical-guidance/Prostate-Cancer-Detection.pdf
National Comprehensive Cancer Network
Testing
Digital Rectal Exam
(optional, see
Prostate Cancer
for efficacy)
Prostate Specific Antigen (PSA)
Timing (if screening is performed)
Start screening (some recommend every other year)
Normal risk: Starting at age 50 years old (ACP, ACS) or age 55 (AUA)
High Risk: Starting at age 40 years old (AUA) or 45 years old (ACS)
See
Prostate Cancer
for risks factors
Black Male
Young first degree relative (<age 65 years old) with
Prostate Cancer
Known
Genetic Syndrome
s (e.g.
BRCA1
,
BRCA2
,
Lynch Syndrome
)
Stop screening
Stop screening by age 70 years old OR
Less than 10 to 15 years
Life Expectancy
(ACS/AUA)
See
Charlson Comorbidity Index
(CALE)
Frequency of testing
Every 2 to 4 years is the interval recommended by most organizations
Annual screening increases
False Positive
risk without mortality benefit
ACS recommends every 2 years for PSA <2.5 ng/ml, and every year for PSA >=2.5 ng/ml
High risk patients (e.g.
BRCA2
) may be considered for annual screening
Screening every 4 years may be as effective as annual
van der Cruijsen-Koeter (2003) J Natl Cancer Inst 95 [PubMed]
References
Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]
Documentation
Informed Consent
Discussion with Patient
Prostate Cancer
is common
Second most common cancer in U.S. men (
Lung Cancer
is first)
Over 299,000 new cases of
Prostate Cancer
each year in the United States (as of 2024)
Lifetime risk of
Prostate Cancer
is 17% (higher risk if Black or positive
Family History
)
Most
Prostate Cancer
occurs in men over age 65 (60%)
Blood Test improves detection of
Prostate Cancer
PSA is twice as effective as
Digital Rectal Exam
PSA blood test is far from perfect
Most PSA level increases are not due to
Prostate Cancer
As high as 70% of men with an abnormal PSA do not have
Prostate Cancer
PSA misses as many as 15-20% of
Prostate Cancer
s (PSA <4)
Early detection, however may not save more lives
Only 3% of men die from
Prostate Cancer
Most
Prostate Cancer
s do not affect men who have them
Prostate Cancer
most often affects those over age 75 years old (70% of
Prostate Cancer
deaths)
Increased PSA level triggers invasive evaluation
Urology
Consultation
Transrectal
Ultrasound
with
Prostate
biopsies
Most
Prostate Cancer
is treated surgically
Prevents death in only 10% men with
Prostate Cancer
Prostate
removal has high morbidity and a risk of mortality
Death: 2%
Erectile Dysfunction
: 25%
Urethral Stricture
: 18%
Incontinence
: 6%
Interpretation
Age specific Normal PSA values
Age 40 to 49 years
White: PSA <= 2.5
Black: PSA < 2.0
Asian: PSA < 2.0
Age: 50 to 59 years
White: PSA <= 3.5
Black: PSA < 4.0
Asian: PSA < 3.0
Age 60 to 69 years
White: PSA <= 4.5
Black: PSA < 4.5
Asian: PSA < 4.0
Age 70 to 79 years
White: PSA <= 6.5
Black: PSA <5.5
Asian: PSA <5.0
Interpretation
Algorithym to evaluate PSA results
PSA < 2 ng/ml
Repeat PSA in 2 years
Chance that PSA > 5 ng/ml in 2 years is <4%
Carter (1997) JAMA 277(18) [PubMed]
PSA 2.6 to 4.0 ng/ml
Unclear guidelines as to approach this range of PSAs
False Positive Rate
would be 80% if PSA threshold were 2.5 ng/ml
False Negative Rate
15% (of which 15% are high grade
Prostate Cancer
s)
Some groups have suggested referral in this range for ages 40 to 50 years (esp. black men)
PSA 4.0 to 5.0 ng/ml
Prostate Cancer
"Curable" Range
Test Sensitivity
: 72%
Test Specificity
: 93%
Positive Predictive Value
: 25%
False Positive Rate
: 70%
PSA >5.0 ng/ml
Lower likelihood of
Prostate Cancer
"Cure"
Interpretation
PSA values predict
Prostate
size
Prostate
size predicts BPH response to certain therapy
5a-Reductase Inhibitor
s (e.g.
Finasteride
) work best if
Prostate
>40 ml in volume
PSA values suggesting
Prostate
>40 ml volume (
Test Sensitivity
and
Specificity
>70%)
Age 50-59: PSA >1.6 ng/ml
Age 60-69: PSA >2.0 ng/ml
Age 70-79: PSA >2.3 ng/ml
Roehrborn (1999) Urology 53(3):581-9 [PubMed]
Prognosis
Prognostic Predictive Value of PSA
PSA with associated
Prostate
ctomy findings
PSA <= 4.0 ng/ml
Organ limited
Prostate Cancer
in 64%
PSA 4.0-10.0 ng/ml
Organ limited
Prostate Cancer
in 50%
PSA 10.0 to 20.0 ng/ml
Organ limited
Prostate Cancer
in 35%
PSA >100 ng/ml
Predicts bone metastases in 74% of cases
PSA in combination with
Rectal Exam
and biopsy
PSA < 10 ng/ml (Non-palpable, Low Gleason grade)
Organ limited disease in 60%
PSA >20 ng/ml (Palpable, Gleason poor-moderate differentiated)
Organ limited disease in 10%
Management
Increased PSA
Recheck elevated PSA (>4 ng/ml) in 3 months
Transient PSA increase (e.g. due to BPH,
Prostatitis
) will normalize on recheck in 25 to 40% of patients
Antibiotic
s are not recommended for elevated PSA unless symptomatic
Prostatitis
is present
Additional Testing to consider on consistently elevated PSA (to further risk stratify to those who need biopsy)
Multipara
metric MRI (see
Prostate Cancer
)
PSA Kinetics
Biomarkers
Blood Biomarkers (e.g. 4Kscore, isoPSA, Proclarix)
Urine Biomarkers (e.g. PCA3, MPS, SelectMDx)
Farha (2022) Ther Adv Urol 14:17562872221103988 +PMID: 35719272 [PubMed]
MyProstateScore (MPS)
Consider in patients referred for
Prostate
biopsy
Estimates risk of
Prostate Cancer
using 2 urinary biomarkers
Prostate Cancer
Antigen
3 (PCA3)
TMPRSS2:ERG
Gene
Fusion
Cost of $760 is not covered by
Medicare
or medicaid
However private insurance may cover
References
Balloga (2022) Am Fam Physician 105(5): 542-3
Prostate
Biopsy indications
PSA >4 ng/ml or
PSA 2.5 to 4.0 ng/ml and
Prostate Cancer Risk Factor
or
Free PSA
<8% of total PSA or
Rapid PSA increase in one year
Baseline PSA <4 ng/ml and PSA increase by more than 0.35 ng/ml in last year or
Baseline PSA 4-10 ng/ml and PSA increase by more than 0.75 ng/ml in last year
References
Brawer (1995) CA Cancer J Clin 45(3):148-64 [PubMed]
Gann (1995) JAMA 273(4):289-94 [PubMed]
Lefevre (1998) Am Fam Physician 58(2): 432-8 [PubMed]
Luttge (1996) Postgrad Med 100(3): 90-102 [PubMed]
Mistry (2003) J Am Board Fam Pract 16(2): 95-101 [PubMed]
Mohan (2011) Am Fam Physician 84(4): 413-20 [PubMed]
Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]
Roehrborn (1999) Urology 53(3):473-80 [PubMed]
Roehrborn (1999) Urology 53(3):581-9 [PubMed]
Slawin (1995) CA Cancer J Clin 45(3):134-47 [PubMed]
Thompson (2004) N Engl J Med 350:2239-46 [PubMed]
Vashi (1997) Mayo Clin Proc 72:337-44 [PubMed]
Wilbur (2008) Am Fam Physician 78(12): 1377-4 [PubMed]
Xu (2024) Am Fam Physician 110(5): 493-9 [PubMed]
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