What are the Canadian Urological Association (CUA) guidelines for managing localized prostate cancer in patients with varying risk profiles and comorbidities?

CUA Guidelines for Localized Prostate Cancer

The Canadian Urological Association (CUA) guidelines are not directly represented in the provided evidence; however, the AUA/ASTRO/SUO guidelines (2018) provide the most comprehensive and recent North American framework for managing localized prostate cancer, which closely aligns with CUA recommendations and should guide clinical practice. 1

Risk Stratification Framework

Risk stratification is the foundation of all treatment decisions and must incorporate clinical T stage, PSA level, Grade Group (Gleason score), and biopsy tumor volume 2:

Very Low Risk

• Clinical stage T1c, Grade Group 1 (Gleason ≤6), PSA <10 ng/mL, <3 positive biopsy cores, ≤50% cancer in any core, PSA density <0.15 ng/mL/g 3

Low Risk

• Clinical stage T1-T2a, Grade Group 1 (Gleason ≤6), PSA <10 ng/mL 2

Intermediate Risk (Favorable vs Unfavorable)

• Favorable: Grade Group 2 (Gleason 3+4=7) with PSA <10 ng/mL 2
• Unfavorable: Grade Group 2 with PSA 10-20 ng/mL, or Grade Group 3 (Gleason 4+3=7) with PSA <20 ng/mL, or clinical stage T2b-T2c 1, 2

High Risk

• Clinical stage ≥T3a, Grade Group 4-5 (Gleason 8-10), or PSA >20 ng/mL 2

Shared Decision-Making Requirements

All treatment decisions must incorporate structured shared decision-making that explicitly addresses cancer severity, patient values, life expectancy, baseline functional status, and potential for salvage treatment. 1

• Patients must meet with multiple specialists (urology and radiation oncology) when feasible to ensure informed decision-making 1
• Clinicians must inform patients about immediate and long-term morbidity of all proposed treatments 1
• Patients should be counseled about modifiable risk factors including smoking and obesity 1

Management by Risk Category

Very Low and Low Risk Disease

Active surveillance is the recommended standard of care for very low risk disease and should be recommended for most low risk patients. 1

• Very low risk patients have <1% metastatic progression rate at 15 years on active surveillance 1
• Low risk patients face approximately 3% prostate cancer-specific mortality risk with active surveillance 1
• No abdominal-pelvic CT or bone scans should be performed for staging in asymptomatic very low or low risk patients 1

For low risk patients who elect definitive treatment (those with risk factors for progression or patient preference), options include: 1

• Radical prostatectomy (with or without nerve-sparing technique)
• External beam radiotherapy (EBRT) or brachytherapy as single modality 1

Watchful waiting (observation without intent to treat) should be recommended for patients with life expectancy ≤5 years. 1

Intermediate Risk Disease

Treatment approach depends on favorable versus unfavorable classification: 1

Favorable Intermediate Risk

• Active surveillance may be offered to select patients, though this carries higher metastatic risk than definitive treatment 1
• Single modality options: radical prostatectomy, EBRT, or brachytherapy (alone or combined) 1
• Short-term ADT (4-6 months) may be considered with radiotherapy, though evidence is less robust than for high-risk disease 1

Unfavorable Intermediate Risk

• Radical prostatectomy with pelvic lymph node dissection (PLND) is recommended 1, 3
• EBRT combined with brachytherapy boost, with or without short-term ADT 1, 3
• Patients should be counseled about potential adjuvant radiotherapy if locally extensive disease is found at prostatectomy 1

Cryosurgery may be considered in select intermediate risk patients, but evidence is limited. 1

Observation/watchful waiting is recommended for life expectancy ≤5 years. 1

High Risk Disease

Radical prostatectomy with PLND or radiotherapy plus ADT (24-36 months) are the only recommended standard treatment options. 1, 3

Key evidence supporting this recommendation:

• SPCG-4 trial showed 15-year prostate cancer-specific mortality of 14.6% with surgery versus 20.7% with watchful waiting (RR 0.62,95% CI 0.44-0.87) 1
• PIVOT trial demonstrated significantly lower bone metastases rates with surgery at 10-12 years 1

For patients receiving EBRT plus ADT, brachytherapy boost (low or high dose rate) should be offered to eligible patients. 1

Active surveillance is not recommended for high risk disease; watchful waiting should only be considered in asymptomatic men with life expectancy ≤5 years. 1

Primary ADT alone should not be used unless the patient has both limited life expectancy and local symptoms. 1

Cryosurgery, HIFU, and focal therapy are not recommended outside clinical trials. 1, 3

Surgical Considerations

When radical prostatectomy is selected 1:

• Robotic/laparoscopic or perineal approaches result in less blood loss than retropubic approach 1
• Nerve-sparing technique provides better erectile function recovery 1
• PLND should be performed for unfavorable intermediate or high risk disease 1
• Older men experience higher rates of permanent erectile dysfunction and urinary incontinence 1, 3
• Neo-adjuvant ADT or systemic therapy should not be used outside clinical trials 1

Radiation Therapy Considerations

For low risk disease: Single modality EBRT or brachytherapy 1

For favorable intermediate risk: EBRT or brachytherapy alone or in combination 1

For high risk disease: 24-36 months ADT must be combined with EBRT (with or without brachytherapy boost) 1, 3

• Patients must be informed that ADT with radiation increases likelihood and severity of sexual dysfunction and causes systemic side effects 1, 3
• Brachytherapy can exacerbate urinary obstructive symptoms 1, 3
• Patients with pre-existing obstructive urinary symptoms may be better candidates for surgical approaches 1

Staging Investigations

Imaging should be risk-stratified: 1

• Very low/low risk: No CT, MRI, or bone scan required 1
• Intermediate/high risk: Bone scan indicated if PSA >20 ng/mL, Gleason score ≥8, or clinical stage T3-T4 1
• Pelvic imaging (CT/MRI): Consider if T3-T4 disease or nomogram indicates >20% lymph node involvement risk 1

Special Populations and Considerations

African American men have two-fold risk of reclassification on first surveillance biopsy and require careful counseling. 1

Men with BMI >35 kg/m² have three-fold increased risk of reclassification to higher risk disease on surveillance. 1

Men with PSA density >0.15 ng/mL have higher risk of progression on active surveillance. 1

Patients with strong family history of aggressive prostate cancer or other cancers (breast, ovarian, pancreatic) should be referred for genetic counseling. 1

Common Pitfalls to Avoid

• Do not use primary ADT for localized disease—it does not improve survival 1, 3
• Do not recommend HIFU or focal therapy as standard care options due to lack of comparative evidence 1, 3
• Do not perform unnecessary staging imaging in low-risk patients 1
• Do not offer active surveillance to high-risk patients 1
• Do not use neo-adjuvant hormonal therapy before prostatectomy outside trials 1