What is the recommended approach for managing low-risk prostate cancer through active surveillance?

Active Surveillance for Low-Risk Prostate Cancer

Active surveillance should be recommended as the best available care option for very low-risk prostate cancer patients and as the preferable care option for most low-risk prostate cancer patients. 1

Patient Selection Criteria

Very Low-Risk Disease (Strong Recommendation for Active Surveillance)

• Clinical stage T1c
• Gleason score ≤6 (ISUP Grade Group 1)
• PSA <10 ng/mL
• <3 positive biopsy cores
• ≤50% cancer involvement in any core
• PSA density <0.15 ng/mL/g
• Life expectancy ≥20 years 1, 2

Low-Risk Disease (Preferred Option for Active Surveillance)

• Clinical stage T1-T2a
• Gleason score ≤6
• PSA <10 ng/mL
• Life expectancy ≥10 years 1

Patients Who May Not Be Ideal Candidates

Men with the following characteristics require careful counseling about potential progression risk:

• Family history of aggressive prostate cancer with early metastasis 1
• Body mass index >35 kg/m² (threefold increased risk of reclassification) 1
• African American race (twofold risk of reclassification on first biopsy) 1
• PSA density >0.15 ng/mL (higher risk of progression) 1

Monitoring Protocol

PSA Testing

• Every 3-6 months (no more frequently than every 6 months unless clinically indicated) 1, 2

Digital Rectal Examination

• Every 6-12 months (no more frequently than every 12 months unless clinically indicated) 1, 2

Confirmatory Biopsy

A confirmatory biopsy is critical to exclude understaging:

• Perform within 6-12 months of initial diagnosis 1, 2
• Required if initial biopsy had <10 cores 1
• Required if assessment was discordant (e.g., palpable tumor contralateral to positive biopsy side) 1
• Should include both systematic and targeted biopsies 2

Surveillance Repeat Biopsies

• Perform at least once every 3 years for the first 10 years 1, 2
• Consider annual biopsies in younger men with longer life expectancy 1
• Not indicated when life expectancy <10 years 1

MRI Considerations

• Consider multiparametric MRI before confirmatory biopsy if not performed before initial biopsy 2
• May be considered if PSA increases and systematic biopsy is negative to exclude anterior cancer 1

Triggers for Intervention

Patients should transition to curative treatment when any of the following occur:

Biopsy-Based Triggers

• Primary Gleason grade 4 or 5 found on repeat biopsy 1
• Upgrade to ISUP Grade Group 2 or higher 1
• Increased number of positive cores (>3 cores) 1
• Increased cancer involvement (>50% in any core) 1

PSA-Based Triggers

• PSA doubling time <3 years 1

Clinical Examination Triggers

• Change in digital rectal examination findings 1

Imaging Triggers

• Progression on MRI (upgrade in PIRADS grade, new lesion, increase in index lesion size) 1

Oncologic Outcomes

Active surveillance demonstrates excellent cancer-specific survival:

• 99% disease-specific survival at 8 years for low-risk disease 1
• Prostate cancer-specific mortality only 2.4% at 10 years 2
• Cancer-specific mortality 0.5-3% at 10-15 years 3
• 96% biochemical recurrence-free progression probability at 5 years for true Gleason 6 disease 2

The evidence supporting active surveillance safety is robust: A 74% reduction in disease-specific mortality was observed in patients diagnosed during the PSA era (1992-2002) compared to earlier periods 1. Long-term follow-up shows metastatic progression rates <1% at 15 years for very low-risk patients 1.

Treatment-Related Considerations

Immediate treatment carries significant morbidity without clear mortality benefit in low-risk disease:

• Radical prostatectomy increases erectile dysfunction by 35% (80% vs 45%) and urinary leakage by 28% (49% vs 21%) compared to watchful waiting 1
• Treatment enhances quality-adjusted survival by only 1.2 months in low-risk patients 2
• Approximately 55% of low-risk patients receive unnecessary treatment 2

Common Pitfalls to Avoid

Inadequate Initial Biopsy Sampling

Clinical understaging is a major concern: About 30% of patients initially classified as low-risk harbor higher-grade disease on confirmatory biopsy 4, 3. This is why the confirmatory biopsy within 6-12 months is non-negotiable for patients selecting active surveillance 1, 2.

Overreliance on PSA Kinetics Alone

PSA doubling time is unreliable as the sole monitoring parameter for detecting progression that remains curable 1. Systematic repeat biopsies remain essential even when PSA is stable 1.

Inappropriate Patient Selection

Do not offer active surveillance to:

• Patients with high-risk disease (better 5-year survival with active intervention) 1
• Patients with ISUP Grade Group 3 or higher 1
• Patients unwilling or unable to comply with rigorous monitoring 1

Insufficient Monitoring Intensity

Real-world data shows that monitoring often falls short of guideline recommendations, with only 42% receiving surveillance biopsies within the first year 5. Adherence to the protocol is critical for safety 5.

Alternative Management for Specific Scenarios

Life Expectancy <10 Years

Observation (not active surveillance) is preferred: This involves monitoring until symptoms develop or are imminent (PSA >100 ng/mL), then initiating palliative androgen deprivation therapy 1. Repeat biopsies are not indicated in this population 1.

Select Low-Risk Patients with High Progression Risk

Definitive treatment (radical prostatectomy or radiotherapy) may be offered to select low-risk patients with high probability of progression, such as those with multiple risk factors for reclassification 1. However, this represents a minority of cases, and the default should remain active surveillance 1.