Prostate Specific Antigen

See Also

Efficacy
PSA

USPSTF Strength of Recommendation: D
Test Sensitivity
1. Overall: 79-82% (72% for a PSA >4 ng/ml)
2. Cancers >1 cm: 90%
3. More sensitive than Digital Rectal Exam (30% for 1 cm tumor)
4. Much more sensitive than Acid Phosphatase
Test Specificity
1. Overall: 59% (93% for a PSA >4 ng/ml)
2. Positive Predictive Value: 25% (for PSA>4 ng/ml)
3. False Positive Rate: 70% (for PSA >4 ng/ml)
4. Benign Prostatic Hyperplasia often increases PSA
Outcomes uncertain despite effective screening
1. Screening does not decrease overall or Prostate Cancer specific mortality
  1. Ilic (2013) Cochrane Database Syst Rev 1:CD004720 [PubMed]
2. Detection may not impact morbidity
  1. May actually increase morbidity due to Prostate Cancer treatment complications
3. Absolute Risk Reduction: 1.28 deaths per 1,000 men screened for Prostate Cancer
4. To prevent one death from Prostate Cancer
  1. Number Needed to Screen: 781
  2. Number Needed to Treat: 27
5. References
  1. Schroder (2014) Lancet 384(9959): 2027-35 [PubMed]
Additional tests that improve PSA efficacy
1. Free PSA to Total PSA ratio
  1. Normal range varies by age, but ratio <25% is higher risk
2. Rate of PSA change
  1. Consider referral for higher rate of change, even if <4 ng/ml
3. MyProstateScore (MPS)
  1. Consider in patients referred for Prostate biopsy
  2. Estimates risk of Prostate Cancer using 2 urinary biomarkers
    1. Prostate Cancer Antigen 3 (PCA3)
    2. TMPRSS2:ERG Gene Fusion
  3. Cost of $760 is not covered by Medicare or medicaid
    1. However private insurance may cover
  4. References
    1. Balloga (2022) Am Fam Physician 105(5): 542-3

Causes
Elevated PSA

Prostate Cancer
Benign Prostatic Hyperplasia (BPH)
Prostatitis
Prostate inflammation, Trauma, or manipulation
Prostatic infarction
Recent sexual activity
Urologic procedures
1. Cystoscopy
2. Urinary Catheterization

Screening
Recommendations

Most organizations can not recommend for or against screening based on lack of evidence
1. See Efficacy above
2. US Preventive Task Force
3. American College of Physicians
4. American Society of Internal Medicine
5. National Cancer Institute
6. Centers for Disease Control and Prevention (CDC)
7. American Academy of Family Physicians
8. American College of Preventive Medicine
Organizations that advocate Shared Decision Making for men ages 55 to 69 years old, but not routine screening
1. American Cancer Society
  1. Smith (2013) CA Canc J Clin 63(2): 88-105 [PubMed]
2. American Urological Association
  1. https://www.auanet.org/common/pdf/education/clinical-guidance/Prostate-Cancer-Detection.pdf
3. National Comprehensive Cancer Network
Testing
1. Digital Rectal Exam (optional, see Prostate Cancer for efficacy)
2. Prostate Specific Antigen (PSA)
Timing (if screening is performed)
1. Start screening (some recommend every other year)
  1. Normal risk: Starting at age 50 years old (ACP, ACS) or age 55 (AUA)
  2. High Risk: Starting at age 40 years old (AUA) or 45 years old (ACS)
    1. See Prostate Cancer for risks factors
    2. African Americans
    3. Young first degree relative (<age 65 years old) with Prostate Cancer
2. Stop screening
  1. Stop screening by age 70 years old OR
  2. Less than 10 to 15 years Life Expectancy (ACS/AUA)
    1. See Charlson Comorbidity Index (CALE)
3. Frequency of testing
  1. Every 1-2 years
  2. Screening every 4 years may be as effective as annual
    1. van der Cruijsen-Koeter (2003) J Natl Cancer Inst 95 [PubMed]
4. References
  1. Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]

Documentation
Informed Consent Discussion with Patient

Prostate Cancer is common
1. Second most common cancer in U.S. men (Lung Cancer is first)
2. Over 233,000 new cases of Prostate Cancer each year in the United States (as of 2014)
3. Lifetime risk of Prostate Cancer is 17% (higher risk if Black or positive Family History)
  1. Most Prostate Cancer occurs in men over age 65 (60%)
Blood Test improves detection of Prostate Cancer
1. PSA is twice as effective as Digital Rectal Exam
PSA blood test is far from perfect
1. Most PSA level increases are not due to Prostate Cancer
  1. As high as 70% of men with an abnormal PSA do not have Prostate Cancer
2. PSA misses as many as 15-20% of Prostate Cancers (PSA <4)
Early detection, however may not save more lives
1. Only 3% of men die from Prostate Cancer
2. Most Prostate Cancers do not affect men who have them
3. Prostate Cancer most often affects those over age 75 years old (70% of Prostate Cancer deaths)
Increased PSA level triggers invasive evaluation
1. Urology Consultation
2. Transrectal Ultrasound with Prostate biopsies
Most Prostate Cancer is treated surgically
1. Prevents death in only 10% men with Prostate Cancer
2. Prostate removal has high morbidity and a risk of mortality
  1. Death: 2%
  2. Impotence: 25%
  3. Urethral Stricture: 18%
  4. Incontinence: 6%

Interpretation
Age specific Normal PSA values

Age 40 to 49 years
1. White: PSA <= 2.5
2. Black: PSA < 2.0
3. Asian: PSA < 2.0
Age: 50 to 59 years
1. White: PSA <= 3.5
2. Black: PSA < 4.0
3. Asian: PSA < 3.0
Age 60 to 69 years
1. White: PSA <= 4.5
2. Black: PSA < 4.5
3. Asian: PSA < 4.0
Age 70 to 79 years
1. White: PSA <= 6.5
2. Black: PSA <5.5
3. Asian: PSA <5.0

Interpretation
Algorithym to evaluate PSA results

PSA < 2 ng/ml
1. Repeat PSA in 2 years
2. Chance that PSA > 5 ng/ml in 2 years is <4%
  1. Carter (1997) JAMA 277(18) [PubMed]
PSA 2.6 to 4.0 ng/ml
1. Unclear guidelines as to approach this range of PSAs
2. False Positive Rate would be 80% if PSA threshold were 2.5 ng/ml
3. False Negative Rate 15% (of which 15% are high grade Prostate Cancers)
4. 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
1. Prostate Cancer "Curable" Range
2. Test Sensitivity: 72%
3. Test Specificity: 93%
4. Positive Predictive Value: 25%
5. False Positive Rate: 70%
PSA >5.0 ng/ml
1. Lower likelihood of Prostate Cancer "Cure"

Interpretation
PSA values predict Prostate size

Prostate size predicts BPH response to certain therapy
1. 5a-Reductase Inhibitors (e.g. Finasteride) work best if Prostate >40 ml in volume
PSA values suggesting Prostate >40 ml volume (Test Sensitivity and Specificity >70%)
1. Age 50-59: PSA >1.6 ng/ml
2. Age 60-69: PSA >2.0 ng/ml
3. Age 70-79: PSA >2.3 ng/ml
4. Roehrborn (1999) Urology 53(3):581-9 [PubMed]

Prognosis
Prognostic Predictive Value of PSA

PSA with associated Prostatectomy findings
1. PSA <= 4.0 ng/ml
  1. Organ limited Prostate Cancer in 64%
2. PSA 4.0-10.0 ng/ml
  1. Organ limited Prostate Cancer in 50%
3. PSA 10.0 to 20.0 ng/ml
  1. Organ limited Prostate Cancer in 35%
4. PSA >100 ng/ml
  1. Predicts bone metastases in 74% of cases
PSA in combination with Rectal Exam and biopsy
1. PSA < 10 ng/ml (Non-palpable, Low Gleason grade)
  1. Organ limited disease in 60%
2. PSA >20 ng/ml (Palpable, Gleason poor-moderate diff)
  1. Organ limited disease in 10%

Management
Increased PSA

On diagnosis of elevated PSA consider a brief course of empiric therapy for Prostatitis
1. Doxycycline 100 mg orally twice daily for 14-28 days
2. Trimethoprim-Sulfamethoxazole (Septra, Bactrim) DS orally twice daily for 14-28 days
Biopsy indications
1. PSA >4 ng/ml or
2. PSA 2.5 to 4.0 ng/ml and Prostate Cancer risk factor or
3. Free PSA <8% of total PSA or
4. Rapid PSA increase in one year
  1. Baseline PSA <4 ng/ml and PSA increase by more than 0.35 ng/ml in last year or
  2. Baseline PSA 4-10 ng/ml and PSA increase by more than 0.75 ng/ml in last year

References