When is prostate‑specific antigen (PSA) testing indicated in men (age, family history, race, urinary symptoms, abnormal digital rectal exam, monitoring of diagnosed prostate cancer, and before initiating certain medications)?

Indications for PSA Testing in Men

PSA testing should be drawn after shared decision-making in men aged 50–69 with ≥10-year life expectancy, starting earlier at age 45 for African-American men or those with a first-degree relative diagnosed before age 65, and at age 40 for men with multiple affected first-degree relatives diagnosed before age 65. 1, 2, 3

Age-Based Screening Initiation

Average-Risk Men

• Begin PSA screening discussions at age 50 for men with at least 10–15 years of expected survival 1, 2, 3
• Obtain a baseline PSA at age 40 to establish future risk stratification, as PSA above the median at this age predicts future prostate cancer risk better than family history or race alone 1, 2
• PSA measurement in men aged 40–49 is more specific for cancer because benign prostatic hyperplasia is uncommon at this age 2

High-Risk Populations

• African-American men should start at age 45 because they experience approximately 75% higher incidence and more than 2-fold higher mortality compared with non-Hispanic White men 2, 3
• Men with one first-degree relative diagnosed with prostate cancer before age 65 should begin screening at age 45 1, 2, 3
• Men with multiple first-degree relatives diagnosed before age 65 should begin screening at age 40 1, 2, 3

Clinical Indications for PSA Testing

Symptomatic Patients

• Measure serum PSA and perform digital rectal examination (DRE) in patients presenting with urinary symptoms 1
• Any abnormal DRE (palpable nodule, induration, asymmetry) mandates PSA testing and consideration of biopsy regardless of PSA level 1

Monitoring Diagnosed Prostate Cancer

• PSA testing is essential for post-treatment surveillance to detect biochemical recurrence 1, 4
• Serial PSA measurements guide decisions about salvage therapy and disease progression 4

Pre-Treatment Staging

• PSA level is a critical component of risk stratification (low-risk: PSA <10 ng/mL; intermediate-risk: PSA 10–20 ng/mL; high-risk: PSA >20 ng/mL) 1
• PSA correlates directly with prostate cancer aggressiveness and treatment outcomes 4

PSA-Based Screening Intervals

PSA Level (ng/mL)	Recommended Interval	Additional Actions
<1.0	Every 2–4 years	Routine monitoring [2,3]
1.0–2.5	Every 1–2 years	Annual DRE [2,3]
≥2.5	Annually	Consider further evaluation (imaging, biopsy) [2,3]
≥4.0	Repeat PSA; if persistent, proceed to biopsy [1,2]

When to Stop PSA Screening

• Discontinue routine PSA screening at age 70 for most men 1, 2, 3
• Continue beyond age 70 only in exceptionally healthy men with minimal comorbidity, prior elevated PSA values, and life expectancy >10–15 years 1, 2, 3
• Never screen men with <10 years of expected life, as the mortality benefit requires more than a decade to manifest 2, 3

Mandatory Shared Decision-Making

PSA screening must never be performed without an informed, shared decision-making conversation. 1, 2, 3

Benefits to Discuss

• The European Randomized Study of Screening for Prostate Cancer (ERSPC) demonstrated a 20–25% relative reduction in prostate cancer-specific mortality after 13 years of follow-up 1, 5
• Approximately 1.3 fewer prostate cancer deaths per 1,000 men screened over 13 years 2, 5
• 781 men need to be invited for screening and 27 need treatment to prevent one prostate cancer death 1

Harms to Discuss

• False-positive results leading to unnecessary biopsies (50% reduction in false-positives with biennial vs. annual screening) 2
• Biopsy complications including infection, bleeding, and pain 1, 2
• Overdiagnosis and overtreatment of indolent cancers that would never cause symptoms or death 1, 5
• Treatment-related adverse effects: permanent erectile dysfunction (35% increase with surgery), urinary incontinence (28% increase), and bowel dysfunction 1, 2
• No improvement in overall (all-cause) mortality despite reducing prostate cancer-specific deaths 1, 2

Common Pitfalls to Avoid

• Starting screening too late (after age 50) forfeits the opportunity to risk-stratify men when PSA is most predictive 2
• Applying uniform annual screening to all men regardless of PSA level leads to unnecessary testing and higher false-positive rates 2
• Continuing screening beyond age 70 in men with limited life expectancy or significant comorbidities increases harms without benefit 1, 2, 3
• Proceeding to biopsy after a single elevated PSA without confirmation; 40–44% of initially elevated values normalize without intervention 1
• Failing to account for risk factors (race, family history) when determining screening initiation age 2, 3
• Initiating screening without shared decision-making violates all major guideline recommendations 1, 2, 3

Additional Considerations

PSA Refinements

• Free/total PSA ratio helps refine biopsy decisions when PSA is 2.5–10.0 ng/mL 1
• PSA velocity >0.35 ng/mL per year (while PSA <4.0 ng/mL) warrants closer surveillance 2
• PSA density (PSA ÷ prostate volume) with a cutoff of 0.15 ng/mL/cm³ can spare unnecessary biopsies in men with large prostates 2

Before Initiating Certain Medications

• Measure baseline PSA before starting 5-alpha reductase inhibitors (finasteride, dutasteride), as these medications reduce PSA by approximately 50% 1
• Testosterone replacement therapy may affect PSA levels and requires baseline measurement 1