Prostate Specific Antigen

1. See Also
   1. Prostate Cancer
   2. Free PSA
2. Efficacy: PSA
   1. USPSTF Strength of Recommendation: D
   2. Test Sensitivity
      1. Overall: 79-82%
      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 = 59%
      1. High false positive rate
      2. Benign Prostatic Hyperplasia often increases PSA
   4. Positive Predictive Value (PPV) 32-40%
   5. Much more cost-effective than Mammography (due to low cost of PSA Test)
   6. Outcomes uncertain despite effective screening
      1. Detection may not impact morbidity and mortality
   7. Additional tests that improve PSA efficacy
      1. Free PSA to Total PSA ratio (normal range varies by age, but ratio <25% is higher risk)
      2. Rate of PSA change (consider referral for higher rate of change, even if <4 ng/ml)
3. 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
4. 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 advocating screening
      1. American Cancer Society
      2. American Urological Association
      3. National Comprehensive Cancer Network
   3. Screening (if performed)
      1. Men without risk factors: Age over 50 years
         1. Digital Rectal Exam yearly
         2. Prostate Specific Antigen (PSA) yearly
      2. Men with risk factors: Age over 45 years
         1. Indications
            1. See Prostate Cancer for risks factors
            2. African Americans
            3. Young first degree relative with Prostate Cancer
         2. Digital Rectal Exam yearly
         3. Prostate Specific Antigen (PSA) yearly
      3. Age over 70 to 75 years (or life expectancy <10 years)
         1. Discontinue PSA screening
   4. Screening interval
      1. Screening every 4 years may be as effective as annual
      2. van der Cruijsen-Koeter (2003) J Natl Cancer Inst 95
5. 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 200,000 new cases of Prostate Cancer each year in the United States
      3. Lifetime risk of Prostate Cancer is 17% (higher risk if Black or positive Family History)
   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 20% of Prostate Cancers
   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 70
   5. Increased PSA level requires 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. Impotence: 25%
         3. Urethral stricture: 18%
         4. Incontinence: 6%
6. 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
7. Interpretation: Algorithym to evaluate PSA results
   1. PSA < 2 ng/ml
      1. Repeat PSA in 2 years
      2. Chance that PSA > 5 mg/ml in 2 years is <4%
         1. Carter (1997) JAMA 277(18)
   2. PSA 2.6 to 4.0 ng/ml
      1. Unclear guidelines as to approach this range of PSAs
      2. 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
   4. PSA >5.0 ng/ml
      1. Lower likelihood of Prostate Cancer "Cure"
8. 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
9. 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 diff)
         1. Organ limited disease in 10%
10. Management: Increased PSA
    1. 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
    2. Biopsy indications
       1. PSA >4 ng/ml or
       2. PSA 2.5 to 4.0 ng/ml and Prostate Cancer risk 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
11. References
    1. Mohan (2011) Am Fam Physician 84(4): 413-20
    2. Wilbur (2008) Am Fam Physician 78(12): 1377-4
    3. Brawer (1995) CA Cancer J Clin 45(3):148-64
    4. Gann (1995) JAMA 273(4):289-94
    5. Lefevre (1998) Am Fam Physician 58(2): 432-8
    6. Luttge (1996) Postgrad Med 100(3): 90-102
    7. Mistry (2003) J Am Board Fam Pract 16(2): 95-101
    8. Roehrborn (1999) Urology 53(3):473-80
    9. Roehrborn (1999) Urology 53(3):581-9
    10. Slawin (1995) CA Cancer J Clin 45(3):134-47
    11. Thompson (2004) N Engl J Med 350:2239-46
    12. Vashi (1997) Mayo Clin Proc 72:337-44