Prostate Cancer - PSA

Diagnosis

Indications for Testing

• Follow up previously elevated PSA (screening recommendations can be found on the Screening tab); new prostate nodule or hypertrophy

Laboratory Testing

• PSA
  • 4-10 ng/mL indeterminate (2.5-10 ng/mL may be preferred in some cases) – consider PSA velocity testing, PSA free percentage, or PCA3
  • >10 ng/mL – recommend biopsy
  • <3 ng/mL – repeat PSA in 1 year
  • Normal PSA values do not rule out prostate cancer (substantiated by the Prostate Cancer Prevention trial); age-specific reference ranges should not be used for PSA
    • <0.5 ng/mL – 6.6% had cancer
    • 0.6-1.0 ng/mL – 10.1% had cancer
    • 1.1-2.0 ng/mL – 17% had cancer
    • 2.1-3.0 ng/mL – 23.9% had cancer
    • 3.1-4.0 ng/mL – 26.9% had cancer
  • PSA can be elevated in benign conditions
• PSA velocity (PSAV) – biopsy may be considered based on individual risk factors if PSAV result is ≥0.35 ng/mL/year and PSA concentration is >2.6-4 ng/mL (2012 guidelines, National Comprehensive Cancer Network [NCCN])
  • PSA velocity = (PSA test #2-PSA test #1)/time elapsed
• PSA free percentage – helps distinguish prostate cancer from benign conditions
  • Use if PSA concentrations are 4–10 ng/mL and digital rectal exam (DRE) is negative
    • A range of 2.5-10 ng/mL may be preferred in some cases
  • Risk is age dependent – the older the patient and the lower the value, the higher the risk
  • PSA free percentage >25% associated with low risk; PSA free percentage ≤10% associated with ≥49% risk regardless of age
    • PSA free <25% – recommend biopsy
• PSA density (PSAD)
  • PSA/ultrasound volume of prostate gland
  • Higher value associated with increased risk of cancer (typically >0.1 or 0.15)
• PCA3 (urine test) – if PSA is 4-10 ng/mL (2.5-10 ng/mL may be preferred in some cases), or patient has elevated PSA and negative biopsy
  • Collected after prostate massage
  • PCA3 ≥35 – high indication for biopsy
  • Not approved by FDA as diagnostic test

Histology

• Sonographically guided biopsy is current means of diagnosis
  • Recommended if PSA >10 ng/mL or if PSA is 4-10 ng/mL with a free percentage between 10% and 25%
  • Tumors assigned Gleason score based on gland architecture
• Biopsy results determine next step
  • Atypical small acinar proliferation – repeat PSA and DRE in 3 months
  • High-grade intraepithelial dysplasia (PIN 3) – repeat PSA and DRE in 3 months and every 3 months for 1 year
  • Cancer – discuss options
• Immunohistochemistry
  • P504S (AMACR); p63; PSA; HMWCK (keratin 903)

Imaging Studies

• Transrectal ultrasound (TRUS) – measure prostate volume (PV)
  • Divide PSA value by PV to obtain PSAD

Prognosis

• Future risk of cancer
  • PSA baseline above median for age at 40-55 years is a strong predictor of future cancer risk
    • American Urological Association (AUA) recommendation (2009) – begin screening at age 40 and follow more frequently if PSA baseline is above median
• Current cancer
  • Higher initial PSA concentration correlates with increased risk of tumor progression over 10 years and with a finding of metastatic disease at the time of diagnosis
  • Indications of aggressive tumor
    • Higher PSAD (low PSAD defined as <0.15)
    • Higher PSAV (>2 ng/mL/year)
    • High Gleason score

Differential Diagnosis

• Prostatitis – bacterial, fungal, Mycobacterium tuberculosis
• Benign prostatic hypertrophy

Screening

Monitoring

Clinical Background

Prostate cancer is the most frequent malignant neoplasm in men and the sixth most common neoplasm worldwide. Prostate cancer is the second most common cause of cancer death among American men.

Epidemiology

• Incidence – 160/100,000
• Age – risk rises steeply with age
  • <50 years – low risk
  • 75% of cases occur in men ≥65 years
• Sex – exclusively male
• Ethnicity – higher occurrence in African Americans

Risk Factors

• African American ethnicity
• Family history – 5- to 11-fold increase in risk with a first-degree relative diagnosed with prostate cancer <65 years
• Elderly males

Pathophysiology

• Tumors are usually adenocarcinomas that depend on androgens for growth
• Epithelial cells of prostate produce prostate-specific antigen (PSA) and acid phosphatase
  • Production increased with tumors and also with inflammation and hyperplasia
• Most tumors develop in peripheral zone of prostate, commonly in the posterior aspect

Clinical Presentation

• May have signs and symptoms of enlarged prostate – urgency and frequency of urination
• Frequently asymptomatic
• Metastatic disease
  • Bone pain – pelvis, spine
  • Osteoblastic lesions seen by x-ray

Indications for Laboratory Testing

• Tests generally appear in the order most useful for common clinical situations
• Click on number for test-specific information in the ARUP Laboratory Test Directory

Click the plus sign to expand the table of additional tests.

Test Name and Number	Comments
Prostate Specific Antigen, Total - Medicare Screening 0070234 Method: Quantitative Electrochemiluminescent Immunoassay
Prostate Specific Antigen, Total with Reflex to Free PSA (Includes Free Percentage) 0080264 Method: Quantitative Electrochemiluminescent Immunoassay	If PSA total is between 3.0-10.0 ng/mL, free PSA will be added
Prostatic Acid Phosphatase 0070120 Method: Quantitative Chemiluminescent Immunoassay	Of limited clinical utility Benign prostatic hyperplasia, prostate massage, and prostatic infarction may result in elevated PAP concentrations; the PAP assay value, regardless of level, should not be interpreted as absolute evidence for the presence or absence of malignant disease

Diagnostic Algorithm

  Prostate Cancer Screening Algorithm