What are the recommended treatment approaches for a patient with localized prostate cancer according to the Canadian Urological Association (CUA) guidelines?

Management of Localized Prostate Cancer: CUA-Aligned Guidelines

For localized prostate cancer, treatment selection depends on risk stratification and life expectancy: low-risk disease warrants active surveillance in most cases, intermediate-risk disease requires individualized decision-making between surgery and radiation, and high-risk disease demands definitive treatment with radical prostatectomy plus extended lymph node dissection or radiation therapy combined with 24-36 months of androgen deprivation therapy. 1, 2

Risk Stratification Framework

Risk classification is the critical first step that determines all subsequent management decisions 1:

• Low-risk disease: T1-2a, Gleason <7 (ISUP grade group 1), and PSA <10 ng/ml 1
• Intermediate-risk disease: Does not meet low or high-risk criteria; subdivide into favorable (Gleason 3+4, PSA <10, <3 cores positive, <50% core involvement) versus unfavorable 1
• High-risk disease: T3-4, Gleason ≥8 (ISUP grade group ≥4), or PSA >20 ng/ml 1

Treatment Algorithm by Risk Category

Low-Risk Disease

Active surveillance is the preferred approach for most patients with low-risk disease and >10 year life expectancy, avoiding treatment-related morbidity while maintaining curative options 1, 2. This represents a paradigm shift from historical overtreatment patterns.

Active surveillance protocol requirements 3:

• Accurate disease staging with systematic biopsy using ultrasound or MRI guidance 3
• Routine PSA testing and digital rectal examination at least annually 3
• Confirmatory biopsy within the initial 2 years, then surveillance biopsies thereafter 3
• Multiparametric prostate MRI may be incorporated as a surveillance component 3

Triggers for conversion to definitive treatment 3:

• Detection of higher Gleason score than at surveillance initiation (adverse reclassification) 3
• Growth or invasion detected on multiparametric MRI 3
• Suspicious PSA rises that change PSA density 3
• Approximately 20-50% of patients on active surveillance receive treatment within 10 years 3

Alternative definitive treatment for low-risk disease (if patient declines surveillance or has strong preference) 1, 2:

• Single modality external beam radiation therapy (EBRT) or brachytherapy 2
• Radical prostatectomy for younger, healthier patients preferring surgical intervention 2

Intermediate-Risk Disease

Treatment selection for intermediate-risk disease requires distinguishing favorable from unfavorable features 1, 2:

For favorable intermediate-risk disease 2:

• EBRT or brachytherapy alone (without ADT) are acceptable radiation approaches 2
• Radical prostatectomy is appropriate for younger patients with >10 year life expectancy 3, 2
• Active surveillance may be considered in highly selected cases 1

For unfavorable intermediate-risk disease 2:

• Radical prostatectomy with pelvic lymph node dissection is strongly recommended, with consideration of adjuvant radiotherapy if locally extensive disease is found at surgery 2
• EBRT with short-term ADT (4-6 months) is an alternative 2

High-Risk Disease

High-risk localized prostate cancer demands aggressive definitive treatment regardless of comorbidity-adjusted life expectancy 1, 2, 4:

Radiation-based approach 1, 2:

• EBRT plus 24-36 months of ADT is the radiation-based standard with Grade A evidence 2
• Target 76-78 Gy to the prostate using conventional fractionation with IMRT/VMAT plus IGRT 5
• Include pelvic lymph node coverage in radiation field 5

Surgery-based approach 1, 2:

• Radical prostatectomy with extended pelvic lymph node dissection 1, 2
• Extended PLND removes all node-bearing tissue from external iliac vein anteriorly to internal iliac artery proximally 3
• Consider adjuvant radiotherapy for positive surgical margins or extracapsular extension 1

Age and Life Expectancy Considerations

Younger patients (<65 years) with >10 year life expectancy derive greater cancer control benefit from radical prostatectomy than older men 3, 2. This survival advantage is particularly pronounced in healthier, younger patients 3.

For patients >70 years 2:

• Higher rates of permanent erectile dysfunction and urinary incontinence after prostatectomy make radiation relatively more attractive 2
• Radiation therapy becomes the preferred definitive option in this age group 2

For patients with life expectancy ≤5 years, observation or watchful waiting should be recommended regardless of risk category 2.

Surgical Technique Considerations

Robotic/laparoscopic or perineal techniques result in less blood loss than retropubic prostatectomy 3, 2. In experienced hands, laparoscopic and robot-assisted approaches appear comparable to open surgical approaches 3.

Nerve-sparing approaches provide better erectile function recovery than non-nerve-sparing techniques 3, 2. Recovery of erectile function is directly related to age at surgery, preoperative erectile function, and degree of cavernous nerve preservation 3.

Radiation Therapy Options

Multiple radiation modalities are available for localized prostate cancer 3:

• External beam radiation therapy: Uses IMRT or VMAT for conformal treatment with normal tissue sparing 3
• Stereotactic body radiotherapy: Delivers hypofractionated treatment in five or fewer fractions 3
• Low-dose rate brachytherapy: Radioactive seeds implanted based on image-guidance (145 Gy for I-125 Gy for Pd-103) 3
• High-dose rate brachytherapy: Temporary catheters for high-activity radiation source delivery 3
• Combination therapy: EBRT combined with brachytherapy for improved periprostatic coverage 3

Brachytherapy exacerbates urinary obstructive symptoms more than EBRT, making it less suitable for patients with pre-existing lower urinary tract symptoms or previous TURP 3, 2.

Critical Pitfalls to Avoid

Do not use neoadjuvant ADT before radical prostatectomy (Strong Recommendation; Grade A evidence) 3, 2. Neoadjuvant ADT for radical prostatectomy is strongly discouraged 3.

Do not omit ADT when using radiation for high-risk disease—the combination of EBRT plus 24-36 months ADT has Grade A evidence, while radiation alone does not 2, 5. Short-course ADT (4-6 months) is inadequate for high-risk or node-positive disease 5.

Do not recommend cryosurgery, HIFU, or focal therapy as standard care options, as comparative outcome evidence is lacking 2. Whole gland cryosurgery is associated with worse sexual side effects than radiotherapy 3.

Do not omit pelvic lymph node dissection in high-risk disease. Extended PLND discovers metastases approximately twice as often as limited PLND and provides more complete staging 3.

Side Effect Profiles for Shared Decision-Making

Sexual function 3:

• Erectile dysfunction occurs in many patients following prostatectomy or radiation 3
• Ejaculate will be lacking despite preserved ability to attain orgasm after prostatectomy 3
• Observation does not cause sexual dysfunction 3
• ADT combined with radiation significantly increases adverse effects on sexual function 2

Urinary function 3:

• Temporary urinary incontinence occurs in most patients after prostatectomy and persists long-term in a small but significant subset 3
• Incontinence rates are higher after prostatectomy than during observation or after radiation 3
• Long-term obstructive or irritative urinary problems occur in a subset of patients following radiation 3
• Prostatectomy can relieve pre-existing urinary obstruction 3

Bowel/rectal function 3:

• Whole gland cryosurgery has similar bowel/rectal side effects as radiotherapy 3

Post-Treatment Surveillance

Monitor all patients post-therapy with PSA, even though not all PSA recurrences are associated with metastatic disease and prostate cancer-specific death 3.

Salvage radiation therapy to the prostate bed is recommended for biochemical recurrence after prostatectomy, and should be initiated early (PSA <0.5 ng/ml) 1.

ADT is not recommended as routine practice for biochemical recurrence, except in cases with symptomatic local disease, proven metastases, or PSA doubling time <3 months 1.