Treatment of Prostate Cancer
Treatment for prostate cancer must be stratified by disease stage and risk category, with localized low-risk disease managed through active surveillance, intermediate-risk disease treated with surgery or radiation therapy, and metastatic disease requiring androgen deprivation therapy combined with androgen receptor pathway inhibitors (such as abiraterone or darolutamide) as first-line treatment. 1, 2
Risk Stratification Framework
Before selecting treatment, classify patients into risk categories based on PSA level, Gleason score, and clinical stage 3:
- Very Low/Low Risk: Gleason ≤6, PSA <10 ng/mL, stage T1-T2a 3
- Intermediate Risk: Gleason 7 OR PSA 10-20 ng/mL 3
- High Risk: Gleason 8-10 OR PSA >20 ng/mL OR stage ≥T2c 3
Treatment by Disease Stage
Localized Low-Risk Disease (T1-T2, Gleason ≤6, PSA <10)
Active surveillance is the preferred approach for patients with life expectancy ≥10 years, avoiding treatment-related morbidity while maintaining curative options if disease progresses 3, 2, 4. This includes:
- PSA measurement every 6 months 2
- Digital rectal examination every 12 months 2
- Repeat prostate biopsy every 12 months 2
For patients with life expectancy <10 years, observation (watchful waiting) with delayed hormone therapy only if symptomatic progression occurs is recommended 3, 2.
Alternative curative options include radical prostatectomy, external beam radiation therapy (≥66 Gy in 1.8-2.0 Gy fractions), or brachytherapy, all with similar 10-year survival rates of 90-94% 3, 2.
Intermediate-Risk Disease (Gleason 7 OR PSA 10-20)
For patients with life expectancy ≥10 years, radical prostatectomy or external beam radiation therapy are the primary options 3.
When using radiation therapy, neoadjuvant and concurrent androgen deprivation therapy for 4-6 months should be considered, as this significantly improves local control and reduces disease progression 3, 2.
Brachytherapy with or without external beam radiation is an alternative 3.
High-Risk/Locally Advanced Disease (Gleason 8-10 OR PSA >20 OR T3-T4)
External beam radiation therapy plus androgen deprivation therapy for 2-3 years is the recommended first-line treatment, as this significantly improves overall survival 3. The radiation dose should be ≥66 Gy 3.
Radical prostatectomy plus extended pelvic lymphadenectomy can be considered in highly selected cases 3.
For patients with life expectancy <5 years, observation only is appropriate 3.
Metastatic Disease Treatment
First-Line Therapy for Metastatic Hormone-Naïve Disease
Continuous androgen deprivation therapy combined with androgen receptor pathway inhibitors (abiraterone or darolutamide) is the recommended first-line treatment 1, 2. ADT is achieved through:
- Medical castration: LHRH agonists (goserelin, leuprolide) 1, 2
- Surgical castration: Bilateral orchiectomy (equally effective alternative) 1
LHRH analogs must be accompanied by an antiandrogen for the first 4 weeks to prevent testosterone flare 3, 2.
For fit patients with extensive metastatic disease, adding docetaxel chemotherapy to ADT plus darolutamide provides the greatest survival benefit (median OS 53.3 months vs 36.5 months with ADT alone, HR 0.66) 1, 5, 4. Docetaxel is given at 75 mg/m² every 3 weeks as a 1-hour intravenous infusion with prednisone 5 mg orally twice daily 6.
Castration-Resistant Prostate Cancer (CRPC)
Continue androgen deprivation therapy to maintain castrate testosterone levels (<50 ng/dL) 3.
For asymptomatic or mildly symptomatic CRPC, abiraterone or enzalutamide are first-line agents 3. Abiraterone is given at 1,000 mg once daily at least 1 hour before or 2 hours after meals, combined with prednisone 7.
For patients with BRCA1/2 alterations who progress on androgen receptor axis inhibitors, PARP inhibitors (olaparib) can be used (HR 0.69 for OS) 1.
For patients with bone metastases, denosumab or zoledronic acid should be added for skeletal-related event prevention 3, 1.
Chemotherapy options for hormone-resistant disease include docetaxel (which can be rechallenged after progression on novel hormone therapy), mitoxantrone, or cabazitaxel, all combined with prednisone 3, 8.
Post-Treatment Monitoring and Salvage Therapy
After Radical Prostatectomy
PSA should be undetectable (<0.2 ng/mL) within 2 months after surgery 3, 2. Follow-up includes:
- PSA measurement every 3 months during year 1, then every 6 months for 7 years 2
- Digital rectal examination (optional if PSA remains undetectable) 2
For biochemical recurrence (rising PSA), salvage radiation therapy to the prostate bed should be initiated early (PSA <0.5 ng/mL), as this improves outcomes compared to delayed treatment 3, 2.
After Radiation Therapy
PSA should reach ≤1 ng/mL within 16 months 3.
Early androgen deprivation therapy is not routinely recommended for biochemical relapse unless patients have symptomatic local disease, proven metastases, or PSA doubling time <3 months 3.
For patients starting ADT after biochemical relapse following radiation, intermittent ADT is recommended as it has quality-of-life benefits without compromising survival 3.
Critical Management Principles
Patients on long-term ADT should be monitored for osteoporosis and metabolic syndrome, and regular exercise should be recommended to reduce fatigue and improve quality of life 3, 2.
To prevent painful gynecomastia, breast irradiation (8-15 Gy in 1-3 fractions) should be given 1-2 weeks before initiation of antiandrogen therapy 3.
Avoid docetaxel in patients with abnormal liver function (bilirubin >ULN or AST/ALT >1.5× ULN with alkaline phosphatase >2.5× ULN) due to increased risk of severe toxicity and treatment-related mortality 6.
Do not administer docetaxel to patients with neutrophil counts <1500 cells/mm³ 6.