Prostate Specific Antigen

Aka: Prostate Specific Antigen, PSA, Prostate Cancer Prevention, Prostate Cancer Screening

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II. Efficacy: PSA

  1. USPSTF Strength of Recommendation: D
  2. 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
  3. 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
  4. 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]
  5. Additional tests that improve PSA efficacy
    1. See Elevated PSA management below (includes MRI, biomarkers)
    2. Free PSA to Total PSA ratio
      1. Normal range varies by age, but ratio <25% is higher risk
    3. Rate of PSA change
      1. Consider referral for higher rate of change, even if <4 ng/ml

III. Causes: Elevated PSA

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

IV. Screening: Recommendations

  1. 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
  2. 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
  3. Testing
    1. Digital Rectal Exam (optional, see Prostate Cancer for efficacy)
    2. Prostate Specific Antigen (PSA)
  4. 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. Black Male
        3. Young first degree relative (<age 65 years old) with Prostate Cancer
        4. Known Genetic Syndromes (e.g. BRCA1, BRCA2, Lynch Syndrome)
    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 2 to 4 years is the interval recommended by most organizations
        1. Annual screening increases False Positive risk without mortality benefit
        2. ACS recommends every 2 years for PSA <2.5 ng/ml, and every year for PSA >=2.5 ng/ml
        3. High risk patients (e.g. BRCA2) may be considered for annual screening
      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]

V. Documentation: Informed Consent Discussion with Patient

  1. Prostate Cancer is common
    1. Second most common cancer in U.S. men (Lung Cancer is first)
    2. Over 299,000 new cases of Prostate Cancer each year in the United States (as of 2024)
    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%)
  2. Blood Test improves detection of Prostate Cancer
    1. PSA is twice as effective as Digital Rectal Exam
  3. 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)
  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)
  5. Increased PSA level triggers invasive evaluation
    1. Urology Consultation
    2. Transrectal Ultrasound with Prostate biopsies
  6. 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. Erectile Dysfunction: 25%
      3. Urethral Stricture: 18%
      4. Incontinence: 6%

VI. Interpretation: Age specific Normal PSA values

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

VII. Interpretation: Algorithym to evaluate PSA results

  1. 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]
  2. 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)
  3. 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%
  4. PSA >5.0 ng/ml
    1. Lower likelihood of Prostate Cancer "Cure"

VIII. Interpretation: PSA values predict Prostate size

  1. Prostate size predicts BPH response to certain therapy
    1. 5a-Reductase Inhibitors (e.g. Finasteride) work best if Prostate >40 ml in volume
  2. 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]

IX. Prognosis: Prognostic Predictive Value of PSA

  1. 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
  2. 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 differentiated)
      1. Organ limited disease in 10%

X. Management: Increased PSA

  1. Recheck elevated PSA (>4 ng/ml) in 3 months
    1. Transient PSA increase (e.g. due to BPH, Prostatitis) will normalize on recheck in 25 to 40% of patients
    2. Antibiotics are not recommended for elevated PSA unless symptomatic Prostatitis is present
  2. Additional Testing to consider on consistently elevated PSA (to further risk stratify to those who need biopsy)
    1. Multiparametric MRI (see Prostate Cancer)
    2. PSA Kinetics
    3. Biomarkers
      1. Blood Biomarkers (e.g. 4Kscore, isoPSA, Proclarix)
      2. Urine Biomarkers (e.g. PCA3, MPS, SelectMDx)
      3. Farha (2022) Ther Adv Urol 14:17562872221103988 +PMID: 35719272 [PubMed]
    4. MyProstateScore (MPS)
      1. Consider in patients referred for Prostate biopsy
      2. Estimates risk of Prostate Cancer using 2 urinary biomarkers
        1. Prostate CancerAntigen 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
  3. Prostate 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

XI. References

  1. Brawer (1995) CA Cancer J Clin 45(3):148-64 [PubMed]
  2. Gann (1995) JAMA 273(4):289-94 [PubMed]
  3. Lefevre (1998) Am Fam Physician 58(2): 432-8 [PubMed]
  4. Luttge (1996) Postgrad Med 100(3): 90-102 [PubMed]
  5. Mistry (2003) J Am Board Fam Pract 16(2): 95-101 [PubMed]
  6. Mohan (2011) Am Fam Physician 84(4): 413-20 [PubMed]
  7. Mulhem (2015) Am Fam Physician 92(8): 683-8 [PubMed]
  8. Roehrborn (1999) Urology 53(3):473-80 [PubMed]
  9. Roehrborn (1999) Urology 53(3):581-9 [PubMed]
  10. Slawin (1995) CA Cancer J Clin 45(3):134-47 [PubMed]
  11. Thompson (2004) N Engl J Med 350:2239-46 [PubMed]
  12. Vashi (1997) Mayo Clin Proc 72:337-44 [PubMed]
  13. Wilbur (2008) Am Fam Physician 78(12): 1377-4 [PubMed]
  14. Xu (2024) Am Fam Physician 110(5): 493-9 [PubMed]

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