What is the expected increase in Prostate-Specific Antigen (PSA) levels with age?

Expected PSA Increase with Age

PSA levels naturally increase with age, with median values of 0.7 ng/mL for men in their 40s, 0.9 ng/mL for men in their 50s, 1.2 ng/mL for men in their 60s, and 1.5 ng/mL for men in their 70s. 1

Age-Specific PSA Reference Ranges

Age-specific PSA reference ranges vary by ethnicity:

For White Men:

• 40-49 years: 0-2.5 ng/mL 1
• 50-59 years: 0-3.5 ng/mL 1
• 60-69 years: 0-4.5 ng/mL 1
• 70-79 years: 0-6.5 ng/mL 1

For African-American Men:

• 40-49 years: 0-2.0 ng/mL 1
• 50-59 years: 0-4.0 ng/mL 1
• 60-69 years: 0-4.5 ng/mL 1
• 70-79 years: 0-5.5 ng/mL 1

For Asian-American Men:

• 40-49 years: 0-2.0 ng/mL 1
• 50-59 years: 0-3.0 ng/mL 1
• 60-69 years: 0-4.0 ng/mL 1
• 70-79 years: 0-5.0 ng/mL 1

PSA Velocity with Age

PSA velocity (PSAV) also increases with age. Age-adjusted PSA velocity thresholds that may warrant further investigation are:

• 0.25 ng/mL/year in men ages 40-59 1
• 0.50 ng/mL/year in men ages 60-69 1
• 0.75 ng/mL/year in men over 70 1

Clinical Implications

• The annual increase in PSA is approximately 2.4%, while the annual growth of the prostate is about 1.6% 2
• For men with benign prostatic hyperplasia (BPH), prostate volume and PSA have an age-dependent log-linear relationship 3
• To maintain specificity of 70% while detecting prostate glands exceeding 40 mL, age-specific criteria are:
  • PSA > 1.6 ng/mL for men in their 50s 3
  • PSA > 2.0 ng/mL for men in their 60s 3
  • PSA > 2.3 ng/mL for men in their 70s 3

Risk Assessment and Screening Considerations

• Men with PSA levels below the median (<1 ng/mL) at age 60 have only a 0.5% risk of metastases and 0.2% risk of prostate cancer death 1, 4
• Men aged 75 years or older with PSA less than 3.0 ng/mL are unlikely to die from prostate cancer and may safely discontinue screening 1, 4
• Lowering the PSA threshold from 4.0 ng/mL to 2.5 ng/mL would double the number of men defined as abnormal, potentially leading to unnecessary biopsies 5

Important Caveats

• Laboratory variability in PSA testing can range from 20-25% depending on standardization method 1
• Assays using the World Health Organization standard yield results 20-25% lower than those using the Hybritech standard 1
• It is crucial to use the same assay for longitudinal monitoring as PSA assays are not interchangeable 1
• The percentage of free PSA (%fPSA) appears to be independent of age, with median values around 25.3% regardless of age 6
• Consider confirming an abnormal PSA before proceeding to biopsy 1