Understanding Prostate Cancer Screening: Benefits, Risks, and Decision-Making

Table of Contents

• The Clinical Problem: Prostate Cancer Burden
• PSA Testing History and Limitations
• Key Research Findings from Major Studies
• Potential Harms of Screening
• Management After Positive Screening
• Shared Decision Making Process
• Current Screening Guidelines
• Clinical Recommendations
• Study Limitations and Uncertainties
• Source Information

The Clinical Problem: Prostate Cancer Burden

Prostate cancer is currently the most commonly diagnosed cancer (excluding nonmelanoma skin cancer) and the second leading cause of cancer death among men in the United States. In 2022 alone, an estimated 268,500 men were diagnosed with prostate cancer, and approximately 34,500 died from the disease.

The disease primarily affects older men, with the highest incidence occurring among men in their 70s and mortality highest among men in their 80s. Significant racial disparities exist: non-Hispanic Black men have a 1.7 times higher incidence rate and 2.1 times higher mortality rate compared to non-Hispanic White men. Hispanic and Asian men have lower incidence and mortality rates than both White and non-Hispanic Black men.

When detected early while still localized (confined to the prostate), prostate cancer has an excellent 10-year survival rate of approximately 95%. However, when the cancer has spread (metastasized), the 5-year survival rate drops dramatically to approximately 35%.

PSA Testing History and Limitations

Prostate-specific antigen (PSA) is a protein produced by both normal and cancerous prostate cells. The FDA approved PSA testing in 1986 for monitoring patients with known prostate cancer and later in 1994 as a screening tool to detect prostate cancer in men aged 50 and older, used in conjunction with digital rectal examination.

Notably, this approval occurred without evidence that early detection actually improved patient outcomes. The widespread adoption of PSA screening in the late 1980s caused a sharp increase in prostate cancer incidence throughout the 1990s, with rates beginning to decline around 2009.

During this same period, prostate cancer mortality rates decreased by approximately 50% from their peak in the early 1990s and have remained relatively constant since. Research suggests that slightly less than half of this mortality reduction resulted from screening, with the rest attributable to improvements in treatment.

Key Research Findings from Major Studies

Several major randomized controlled trials have examined the effectiveness of PSA screening:

The European Randomized Study of Screening for Prostate Cancer (ERSPC) followed 162,388 men aged 55-69 for 16 years. Men in the screening group received PSA tests every 4 years with a biopsy threshold of 3.0 ng/mL. The study found:

• Prostate cancer diagnoses were 90% higher in the screening group at 9 years and 41% higher at 16 years
• The rate ratio for prostate cancer mortality was 0.80 (95% CI, 0.72 to 0.90) at 16 years
• This translates to preventing 1.76 prostate cancer deaths per 1000 men screened
• The number needed to invite for screening to prevent one prostate cancer death was 570

The U.K. Cluster Randomized Trial of PSA Testing (CAP) involved 419,582 men aged 55-69. Only 36% of men in the intervention group actually underwent the offered one-time PSA screening. At 10-year follow-up:

• Prostate cancer diagnosis was 19% higher in the screening group (rate ratio 1.19)
• No significant difference in prostate cancer mortality was found
• The mortality rate was 0.30 per 1000 person-years in the intervention group versus 0.31 in the control group

The U.S. Prostate, Lung, Colorectal and Ovarian (PLCO) trial included 76,683 men aged 55-74. This study showed limited benefit, likely because many men in the control group also received PSA testing outside the study.

Based on these trials, researchers estimate that screening 1000 U.S. men aged 55-69 may prevent prostate cancer deaths in 1.3 men over the 13 years following initial screening.

Potential Harms of Screening

PSA screening carries several significant risks that patients must consider:

False Positive Results: The cumulative risk of a false positive PSA test is estimated at 10-15% over several screening rounds. Approximately 5% of screenings result in false positives that lead to unnecessary biopsies.

Biopsy Complications: Prostate biopsies carry risks including:

• Infection (occurs in 5-7% of patients, requiring hospitalization in 1-3%)
• Rectal bleeding requiring medical intervention (approximately 2.5%)
• Blood in urine (hematuria, occurring in less than 1%)
• Urinary obstruction or retention
• Temporary erectile dysfunction
• Significant discomfort during the procedure

Overdiagnosis: This occurs when screening detects cancers that would never have caused symptoms or death during a patient's lifetime. Studies estimate that 23-42% of prostate cancers detected through screening between 1985-2000 were overdiagnosed.

Treatment Side Effects: For men who undergo treatment, potential complications include:

• Radical prostatectomy: Substantially increased risks of erectile dysfunction and urinary incontinence
• Radiation therapy: Possible bowel dysfunction and erectile dysfunction
• In the ProtecT trial, radiation therapy was associated with worse bowel function compared to active monitoring

Management After Positive Screening

When a PSA test shows elevated levels (typically above 4.0 ng/mL in the U.S.), several management options are available:

Initial Steps:

1. Repeat the PSA test to confirm results and rule out laboratory error
2. Evaluate for temporary causes of PSA elevation (prostatitis, benign prostate enlargement, recent ejaculation, or vigorous exercise)
3. Antibiotics are not recommended unless infection symptoms are present

Further Assessment Tools: Before proceeding to biopsy, several tests can help assess cancer risk:

• PSA kinetics (changes in PSA levels over time)
• Blood-based tests: Prostate Health Index, 4Kscore Test
• Urine-based tests: PCA3 test
• Stockholm-3 model (combines multiple factors)

Biopsy Procedures:

• Standard approach: 12-core ultrasound-guided systematic biopsy
• Newer approach: Multiparametric magnetic resonance imaging (MRI) followed by targeted biopsy of suspicious areas
• MRI-guided biopsies improve detection of clinically significant cancers and reduce misclassification
• The Prostate Imaging Reporting and Data System (PI-RADS) scores lesions from 1-5, with scores of 3+ typically prompting biopsy

Shared Decision Making Process

Shared decision making is crucial for prostate cancer screening. This process involves open discussion between patients and doctors about:

Benefits of Screening:

• Potential reduction in prostate cancer mortality
• Early detection of aggressive cancers
• Peace of mind from negative results

Risks of Screening:

• False positive results leading to unnecessary procedures
• Biopsy complications
• Overdiagnosis and overtreatment
• Treatment side effects (incontinence, erectile dysfunction)

Patient-Specific Factors:

• Age and life expectancy
• Family history of prostate cancer
• Race and ethnicity (higher risk for Black men)
• Personal values and preferences
• Comfort with uncertainty versus intervention

Decision aids—tools that help patients understand benefits and risks—can improve knowledge and reduce decisional conflict. Studies show they modestly improve patient understanding though they don't significantly change whether patients ultimately choose screening.

Current Screening Guidelines

Professional organizations provide varying recommendations regarding prostate cancer screening:

U.S. Preventive Services Task Force (USPSTF):

• Recommends individualized decision-making for men aged 55-69
• Notes that screening offers a small potential benefit but significant harms
• Recommends against routine screening for men 70+

American Cancer Society:

• Recommends discussing screening at age 50 for average-risk men
• Recommends earlier discussion (age 45) for high-risk men (Black men, those with family history)
• Even earlier discussion (age 40) for highest-risk men (multiple family members diagnosed young)

American Urological Association:

• Recommends shared decision-making for men aged 55-69
• Selective screening for men aged 40-54 at higher risk
• Against routine screening for men aged 70+ or with less than 10-15 year life expectancy

All major guidelines emphasize that screening should not occur without a discussion of potential benefits and harms.

Clinical Recommendations

For a 60-year-old man considering prostate cancer screening, we recommend:

1. Engage in Shared Decision Making: Have a detailed conversation with your doctor about your personal risk factors, values, and preferences. Discuss both the potential benefits and harms of screening.

2. Use Decision Aids: Request educational materials or decision aids specifically designed for prostate cancer screening decisions. These tools can help you better understand the complex trade-offs involved.

3. Consider Personal Risk Factors: Take into account your race, family history, and overall health when making your decision. Black men and those with family histories may benefit from earlier or more frequent screening discussions.

4. Understand the Pathway: Recognize that a positive screening test is just the beginning of a process that may involve repeat testing, possible biopsy, and difficult treatment decisions if cancer is found.

5. Know All Options: Understand that active surveillance (monitoring rather than immediate treatment) is a valid approach for low-risk prostate cancers detected through screening.

6. Consider Life Expectancy: Men with less than 10-15 years life expectancy are unlikely to benefit from screening but may still experience harms.

Study Limitations and Uncertainties

Several important uncertainties remain in prostate cancer screening:

Active Surveillance Questions: While active surveillance has proven safe for low-risk cancers, questions remain about:

• Which patients with intermediate-risk (grade group 2) cancers can safely defer treatment
• Optimal monitoring strategies during active surveillance
• The best biomarkers to guide surveillance decisions
• Appropriate triggers for switching from surveillance to treatment

Screening Personalization: It remains unclear whether tailoring screening based on race, genetic risk scores, or other factors actually improves outcomes.

MRI Implementation: Questions persist about the safety of skipping standard biopsies in men with elevated PSA but normal MRI results, particularly for those never previously biopsied.

Long-term Outcomes: More research is needed on the very long-term outcomes (beyond 15-20 years) of screening decisions and treatment approaches.

Source Information

Original Article Title: Screening for Prostate Cancer

Authors: Paul F. Pinsky, Ph.D., and Howard Parnes, M.D.

Publication: The New England Journal of Medicine, April 13, 2023

DOI: 10.1056/NEJMcp2209151

This patient-friendly article is based on peer-reviewed research from The New England Journal of Medicine. It preserves all original data, findings, and clinical recommendations while making the information accessible to educated patients.