What are the causes of elevated Prostate-Specific Antigen (PSA) levels other than cancer?

Non-Cancerous Causes of Elevated PSA Levels

Elevated PSA levels can be caused by multiple non-cancerous conditions, with benign prostatic hyperplasia (BPH), prostatitis, and various forms of prostatic trauma being the most common causes. 1

Common Non-Malignant Causes of Elevated PSA

Benign Prostatic Hyperplasia (BPH)

• Approximately 25% of men with BPH have elevated PSA levels 1
• Larger prostate glands are associated with higher PSA levels 2
• BPH can account for approximately 23% of serum PSA variance in men without prostate cancer 3

Prostatitis

• Both acute and chronic prostatitis can significantly elevate PSA levels 1
• Inflammation accounts for approximately 7% of serum PSA variance in men without cancer 3
• Studies show higher prevalence of both acute inflammation (63% vs 27%) and chronic inflammation (99% vs 77%) in men with elevated PSA compared to those with normal PSA 3

Prostatic/Urethral Trauma

• Recent prostate biopsy: Causes substantial PSA elevation; testing should be postponed for at least 3-6 weeks after biopsy 1
• Traumatic catheterization 1
• Digital rectal examination (DRE): Causes minimal changes in PSA levels 4
• Prostate massage, ultrasonography, and cystoscopic examination: Can cause clinically significant elevations 4

Other Non-Cancerous Causes

• Recent ejaculation: May cause variable increases in PSA 1
• Acute urinary retention: Can lead to elevated PSA levels 4, 2
• Prostatic calculi: Account for approximately 3% of serum PSA variance 3
• Renal failure: Can elevate PSA levels 4
• Prostatic intraepithelial neoplasia (PIN): May cause PSA elevation 4

Medication Effects on PSA

5α-reductase inhibitors (finasteride, dutasteride)

• Typically reduce PSA by approximately 50% within 6-12 months of initiating therapy 5, 1
• This effect is highly variable - after 12 months of treatment, only 35% of men demonstrate the expected 40-60% decrease in PSA 5
• Failure to achieve significant PSA decrease while taking these medications may indicate increased prostate cancer risk 5, 1

Clinical Considerations

PSA Testing Accuracy

• PSA is not cancer-specific: Only about 25% of men with PSA in the 4-10 ng/mL range have a subsequent positive biopsy 5
• False positives are common: Approximately 2 out of 3 men with elevated PSA do not have prostate cancer 5
• False negatives occur: Approximately 1 in 7 men with PSA levels below 4.0 ng/mL have prostate cancer 5, 1

PSA Interpretation

• Consider PSA kinetics: The rate of PSA increase over time (PSA velocity) may be more important than absolute values in predicting cancer risk 5, 1
• Use the same PSA assay for longitudinal monitoring as assays are not interchangeable 1
• Consider confirming an abnormal PSA before proceeding to biopsy 1

Common Pitfalls to Avoid

• Empiric antibiotic use has limited value for improving test performance in asymptomatic men with elevated PSA 5, 1
• Simply doubling measured PSA values in men on 5-ARIs to obtain an adjusted value may result in unreliable cancer detection 5
• Failing to wait an adequate period (3-6 weeks) after prostatic manipulation or trauma before PSA testing 1
• Not considering age-related PSA increases due to increasing prostate volume 1

By understanding these non-cancerous causes of PSA elevation, clinicians can better interpret PSA results and determine appropriate next steps in patient management.