What criteria should be included when choosing a screening test like Prostate-Specific Antigen (PSA) for prostate cancer in high-risk men?

Criteria for Choosing a Prostate Cancer Screening Test

The primary criterion for selecting a prostate cancer screening test is its ability to detect clinically significant, high-grade cancers early enough to enable curative treatment while minimizing detection of indolent disease that would never threaten the patient's life—not simply detecting as many cases as possible. 1

The Fundamental Goal: Detect Aggressive Disease, Not All Disease

The most critical error in screening test selection is prioritizing sensitivity (detecting every cancer) over specificity and clinical relevance. A screening test that detects every prostate cancer would cause massive overdiagnosis and overtreatment, leading to complications including incontinence, impotence, and bowel dysfunction without improving mortality. 1 This is particularly important because autopsy studies show prostate cancer is present in 33% of men over age 50, yet most would never become clinically apparent during their lifetime. 1

Essential Screening Test Criteria (In Order of Priority)

1. Detect Clinically Significant Cancer While Avoiding Indolent Disease

• The test must identify aggressive prostate cancer early enough to cure it before it spreads outside the prostate, while avoiding overdetection of tumors that would never threaten the patient. 1
• The fundamental goal is not to detect as many cases as possible—this approach leads to net harm. 1

2. Adequate Specificity to Prevent False-Positives

• The test must have sufficient specificity to avoid false-positives that lead to unnecessary biopsies, patient anxiety, and potential complications including drug-resistant infections. 1
• PSA testing has poor specificity of only 60-70% at the conventional 4.0 ng/mL cutoff, which is a major limitation. 1
• Biomarker tests and multiparametric MRI can improve specificity and reduce unnecessary biopsies by 20-30%. 1, 2

3. Enable Risk Stratification for Personalized Follow-Up

• The test should enable risk stratification—men with PSA <1.0 ng/mL at age 60 have <0.3% likelihood of prostate cancer death, allowing less intense follow-up. 1
• Men must have at least 10-15 years life expectancy to potentially benefit from screening, as this is the timeframe needed for early detection and treatment to impact outcomes. 1, 3

4. Acceptable to Allow Shared Decision-Making

• The test must be acceptable enough to allow shared decision-making and informed consent, as screening should never occur without patients understanding the benefits, risks, and uncertainties. 1
• Two-thirds of US men reported no discussion with physicians about advantages, disadvantages, or scientific uncertainty regarding PSA screening—this represents inappropriate use. 1

5. Cost-Effectiveness and Availability (Secondary Considerations)

• While cost-effectiveness and wide availability are relevant factors, these are secondary to the test's ability to improve clinical outcomes without causing net harm. 1

Critical Pitfalls to Avoid

Do Not Prioritize Sensitivity Alone

A test that detects every cancer (including all indolent disease) causes massive overdiagnosis and overtreatment with attendant complications. 1 The goal is not to maximize cancer detection but to detect cancers that matter while avoiding those that don't.

Do Not Screen Without Counseling

Screening without discussing potential benefits, limitations, and harms with patients is inappropriate. 1, 3 The decision to undergo PSA-based screening should be individualized after discussion of false-positive results, unnecessary anxiety, biopsies, and potential treatment complications. 3

Do Not Screen Men with Limited Life Expectancy

Screening men over 75 years or those with <10 year life expectancy substantially increases overdetection without mortality benefit. 1, 3 The harms of screening in men older than 70 years are at least moderate and greater than in younger men because of increased risk of false-positive results, diagnostic harms from biopsies, and harms from treatment. 3

Evidence-Based Screening Outcomes

• PSA-based screening programs in men aged 55-69 years may prevent approximately 1.3 deaths from prostate cancer over 13 years per 1,000 men screened. 3
• Screening may also prevent approximately 3 cases of metastatic prostate cancer per 1,000 men screened. 3
• However, about 1 in 5 men who undergo radical prostatectomy develop long-term urinary incontinence, and 2 in 3 men will experience long-term erectile dysfunction. 3

High-Risk Populations Requiring Modified Approach

African-American men and those with first-degree relatives diagnosed with prostate cancer before age 65 should begin screening discussions at age 45, due to higher incidence and mortality. 2, 4 Men at even higher risk (more than one first-degree relative diagnosed before age 65) could begin testing at age 40. 4