Management of Prostate Cancer
Risk-Stratified Treatment Approach
Management of prostate cancer must be tailored to disease stage, risk category, and life expectancy, with active surveillance preferred for low-risk disease, radical treatment (surgery or radiation) for intermediate-risk disease, and combination radiation plus long-term androgen deprivation therapy for high-risk localized disease. 1, 2
Very Low-Risk and Low-Risk Disease (PSA <10, Gleason ≤6, Stage T1-T2a)
Primary Management
- Active surveillance is the preferred approach for very low-risk disease with life expectancy <20 years and for low-risk disease regardless of life expectancy 1, 2
- Active surveillance achieves 96% 5-year biochemical recurrence-free rate and only 2.4% prostate cancer-specific mortality at 10 years 3
Active Surveillance Protocol
- PSA testing every 3-6 months 1
- Digital rectal examination every 6-12 months 1
- Confirmatory prostate biopsy at 12-24 months after initial diagnosis 1
- Minimum 10-12 biopsy cores should be obtained to avoid inadequate sampling 2
Triggers for Intervention
- Increase in Gleason score on repeat biopsy 1
- PSA doubling time <3 years 1, 2
- Patient preference for definitive treatment 1
Alternative Definitive Treatment Options (if surveillance declined)
For patients with ≥10 years life expectancy who decline surveillance:
- Radical prostatectomy reduces prostate cancer death from 29% to 18% at 18 years compared to watchful waiting, but causes higher rates of urinary incontinence and erectile dysfunction 1
- Radiation therapy (external beam or brachytherapy) has similar long-term erectile dysfunction rates to surgery but higher bowel dysfunction rates 1, 2
Intermediate-Risk Disease (PSA 10-20 OR Gleason 7 OR Stage T2b)
Favorable Intermediate-Risk
- Radiation therapy with short-term (4-6 months) androgen deprivation therapy is recommended 4, 1, 2
- Brachytherapy alone is an option for favorable intermediate-risk cases 1, 2
- Active surveillance may be considered in select cases 3
Unfavorable Intermediate-Risk
- Definitive treatment is required for patients with ≥10 years life expectancy 1
- Radical prostatectomy and radiotherapy are equally effective options 2
- Radiation therapy combined with hormonal therapy (2-3 years) is superior to radiotherapy alone for poorly differentiated tumors 4
High-Risk Localized Disease (PSA >20 OR Gleason 8-10 OR Stage T2c-T3)
Standard Treatment
- External beam radiation therapy (dose >70 Gy) combined with long-term (2-3 years) androgen deprivation therapy is the standard approach 4, 1, 2
- This combination is superior to radiotherapy alone for stages T3-T4 4
- Long-term ADT (2+ years) is superior to short-term (4 months), particularly for Gleason 8-10 disease 1
Alternative Option
Critical Contraindication
- Androgen deprivation therapy as primary monotherapy does not improve survival and is NOT recommended 1
- ADT should only be used in combination with radiation therapy 1
Locally Advanced Disease (Stage T3b-T4)
Primary Treatment
- Androgen deprivation therapy (at least 2 years) combined with 3-dimensional radiation therapy 4
- Neoadjuvant or adjuvant hormone therapy should be considered for patients treated with radical radiotherapy 4
Not Recommended
- Neoadjuvant hormonal therapy before radical prostatectomy shows no benefit for T1-T2 disease and should not be used outside clinical trials for T3 disease 4
Post-Treatment Management
After Radical Prostatectomy
- PSA should be measured 1-3 months post-surgery, then every 3 months during year 1, then every 6 months for 7 years if undetectable 4
- For biochemical recurrence, salvage radiotherapy should be initiated early (PSA <0.5 ng/mL) for maximum effectiveness 2
- Adjuvant radiotherapy may be considered for widespread pT3a, pT4 without node involvement, or positive surgical margins 4
- Adjuvant hormonal therapy can be prescribed for node-positive (pN1) patients 4
After Radiotherapy
- PSA determination and digital rectal examination every 6 months indefinitely 4
- Early ADT is not routinely recommended unless symptomatic local disease, proven metastases, or PSA doubling time <3 months 2
Metastatic Disease (N1 or M1)
Hormone-Naïve Metastatic Disease
- Continuous androgen deprivation therapy plus docetaxel chemotherapy is first-line treatment for patients fit enough to receive it 2
- Standard hormonal therapy is recommended for N1/M0 and M1 disease 4
- Surgical castration equals medical castration in efficacy 4
Castration-Resistant Prostate Cancer (CRPC)
- Abiraterone (1,000 mg daily at least 1 hour before or 2 hours after meals) with prednisone 5 mg twice daily 5
- Enzalutamide 2
- Docetaxel chemotherapy 2
- Radium-223 for bone metastases 2
- Denosumab or zoledronic acid for skeletal-related events 2
Treatments NOT Recommended
- Cryosurgery as primary therapy due to lack of long-term comparative data 1
- Pure anti-androgens are associated with poorer outcomes compared to watchful waiting 4
- Combined androgen blockade should not be used routinely 4
- Chemotherapy for nonmetastatic disease is not recommended 4
- Hormonal therapy alone for T1-T2 Nx/M0 disease in absence of progressive disease 4
Critical Pitfalls to Avoid
- Overtreatment of low-risk disease: Approximately 55% of low-risk patients receive unnecessary treatment providing only 1.2 months quality-adjusted survival benefit while causing urinary, sexual, and bowel dysfunction 3
- Delayed salvage radiotherapy: Most effective when PSA <0.5 ng/mL; delaying reduces effectiveness 2
- Ignoring life expectancy: Curative treatment offers minimal benefit when life expectancy <10 years 1, 2, 3
- Inadequate counseling: All patients considered for radical therapy must receive documented counseling regarding all options 4
- Food interactions with abiraterone: Must be taken at least 1 hour before or 2 hours after meals; food increases exposure 5-10 fold 5