What is the recommended method for screening for prostate cancer?

Prostate Cancer Screening Method

Screen for prostate cancer using prostate-specific antigen (PSA) blood testing, with or without digital rectal examination (DRE), but only after shared decision-making with patients who have at least a 10-15 year life expectancy. 1

Who Should Be Offered Screening Discussions

The decision to screen must be individualized based on age, risk factors, and life expectancy:

Average-Risk Men

• Begin discussions at age 50 years for men with at least 10-year life expectancy 1
• Baseline PSA at age 40 can help establish future risk stratification, though this has majority but not uniform consensus 1, 2

High-Risk Men (Earlier Screening Discussions)

• African American men: Begin at age 45 years due to 75% higher incidence rates and more than double the mortality rates compared to non-Hispanic white men 1, 3
• Men with first-degree relative diagnosed before age 65: Begin at age 45 years 1, 3
• Men with multiple first-degree relatives diagnosed before age 65: Begin at age 40 years 1, 3

Men Who Should NOT Be Screened

• Men under age 50 (average risk) 1
• Men over age 69-70 years 1, 4
• Men with life expectancy less than 10-15 years regardless of age 1
• Men over age 80 - three-fourths of cancers detected are overdiagnosed and would never cause clinical problems 5

The Screening Test Itself

PSA Testing Protocol

• Draw standard blood sample measuring serum PSA level 2
• Patients should avoid vigorous exercise and ejaculation for 2 days prior to prevent false elevations 2
• A single elevated PSA should NOT prompt immediate biopsy - verify with a second measurement in 3-6 months 1, 3
• Use the same laboratory assay for serial measurements to ensure consistency 2

PSA Thresholds and Interpretation

• PSA ≥4.0 ng/mL: Traditional threshold for considering further evaluation or biopsy in average-risk men 1, 2
• PSA 2.5-4.0 ng/mL: Consider individualized risk assessment incorporating race, family history, age, DRE findings, and prior biopsy results before proceeding 1
• PSA <2.5 ng/mL: Can extend screening intervals to every 2 years 1
• PSA ≥2.5 ng/mL: Screen yearly 1

Digital Rectal Examination (DRE)

• DRE can be performed with PSA but is optional 1
• DRE is specifically recommended for men with hypogonadism due to reduced PSA sensitivity in this population 1
• DRE combined with PSA increases overall sensitivity for cancer detection compared to either test alone 1, 6
• DRE has minimal effect on PSA levels, unlike other prostate manipulations 2

Factors Affecting PSA Interpretation

Medical Conditions That Elevate PSA

• Prostate cancer, benign prostatic hyperplasia, prostatitis, urethral or prostatic trauma 2

Procedures That Elevate PSA

• Prostate biopsy, cystoscopic examination, prostate massage, transrectal ultrasound 2
• Digital rectal examination has minimal effect 2

Medications Affecting PSA

• 5α-reductase inhibitors (finasteride, dutasteride): Reduce PSA by approximately 50% within 6 months 2
• For patients on these medications: Double the PSA value for comparison with normal ranges, though this becomes less accurate after 3 years of treatment 2

Improving PSA Specificity

When PSA is elevated but below clear biopsy threshold:

• Free/total PSA ratio: Lower proportion of free PSA suggests cancer rather than benign prostatic hyperplasia 2
• PSA velocity: Rate of change over time; yearly increase >0.75 ng/mL may predict malignancy (requires at least 3 measurements over 18 months) 2
• PSA density: Accounts for prostate size; helps differentiate benign prostatic hyperplasia from cancer 2
• Age-specific reference ranges: PSA normally increases with age 2

When to Proceed to Biopsy

The decision should incorporate multiple factors, not PSA alone:

• DRE findings (suspicious nodule or asymmetry) 1, 3
• Ethnicity (African American men at higher risk) 1, 3
• Age and comorbidities 1, 3
• PSA values and trends 1, 3
• Free/total PSA ratio 1, 3
• History of previous negative biopsy 1, 3
• Patient values and preferences 1, 3

Biopsy Technique

• Transrectal ultrasound-guided biopsy under antibiotic cover and local anesthesia 1, 3
• Minimum 10-12 cores obtained (extended pattern including sextant plus lateral peripheral zone) 1, 3
• Before repeat biopsy: Multi-parametric MRI recommended with consideration for MRI-guided or MRI-TRUS fusion biopsy 1, 3

Benefits and Harms of Screening

Potential Benefits

• European trial (ERSPC): 21% reduction in prostate cancer-specific mortality (29% adjusted for non-compliance) in men aged 55-69 after 13 years 1, 3
• Absolute benefit: Prevents approximately 1.3 deaths per 1,000 men screened over 13 years 3, 4
• Prevents approximately 3 cases of metastatic disease per 1,000 men screened 4

Number Needed to Screen/Treat

• 781 men need to be invited for screening to prevent one prostate cancer death 1, 3
• 27 patients need to be treated to prevent one death 1, 3

Harms of Screening

• False-positive results: PSA specificity only 65-87%, leading to unnecessary anxiety and biopsies 2, 7
• Overdiagnosis: Up to 50% of screen-detected cancers would never cause symptoms or death 1, 7
• Biopsy complications: Infection, bleeding, pain (though no deaths attributed to biopsy) 7
• Treatment complications:
  • 1 in 5 men develop long-term urinary incontinence after radical prostatectomy 4
  • 2 in 3 men experience long-term erectile dysfunction 4
  • Bowel symptoms from radiation therapy 4

Critical Pitfalls to Avoid

• Do not screen men over age 70 or those with life expectancy <10-15 years - harms exceed benefits 1, 5
• Do not proceed to biopsy based on single elevated PSA - always confirm with repeat testing 1, 3
• Do not screen without informed decision-making discussion about benefits, harms, and uncertainties 1
• Do not forget to adjust PSA interpretation for men on 5α-reductase inhibitors 2
• Do not start screening too early in average-risk men (before age 50) - increases overdiagnosis without mortality benefit 1

Conflicting Evidence

The two highest-quality trials provide contradictory results:

• ERSPC (European trial): Showed significant 16% reduction in prostate cancer mortality (RR 0.84,95% CI 0.73-0.95) 7
• PLCO (US trial): Showed no benefit (RR 1.15,95% CI 0.86-1.54) 7
• Meta-analysis of both trials together: No significant difference (RR 0.96,95% CI 0.70-1.30) 7

This discrepancy likely reflects high contamination rates in the PLCO control arm (76 PSA tests per 1,000 person-years) 8 and differences in screening protocols. The ERSPC used more stringent protocols and had less contamination 1.

Given this uncertainty, screening must involve shared decision-making where patients understand that benefits are small and uncertain, while harms are frequent and well-documented 1, 4.