Treatment Options for Prostate Cancer
Treatment for prostate cancer must be stratified by disease stage and risk category, with localized disease managed through active surveillance, surgery, or radiation therapy, while metastatic disease requires androgen deprivation therapy (ADT) combined with novel androgen receptor pathway inhibitors or chemotherapy. 1
Risk Stratification Framework
Risk classification is mandatory before selecting treatment, as it determines prognosis and guides all therapeutic decisions 1. The categories include:
- Very low/low risk: Gleason score ≤6, PSA <10 ng/mL, clinical stage T1c-T2a 1, 2
- Intermediate risk: Gleason score 7, PSA 10-20 ng/mL, or clinical stage T2b 1, 3
- High risk: Gleason score 8-10, PSA >20 ng/mL, or clinical stage ≥T3a 4, 1
Staging workup for intermediate and high-risk disease requires bone scintigraphy and cross-sectional imaging (CT or MRI) to evaluate for metastases, with nodal staging performed using CT, MRI, choline PET/CT, or pelvic lymph node dissection 4, 1.
Treatment by Risk Category
Very Low and Low Risk Disease
For patients with life expectancy <10 years, observation (watchful waiting) is recommended, involving monitoring without immediate curative intent, with delayed hormone therapy only if symptomatic progression occurs 1.
For patients with life expectancy ≥10 years, active surveillance is the preferred option 1, 2. The protocol includes:
- PSA measurement every 6 months 1, 2
- Digital rectal examination every 12 months 1, 2
- Repeat prostate biopsy every 12 months 1, 2
- First follow-up visit at 3 months to establish baseline 2
Active surveillance avoids treatment-related morbidity while maintaining the option for curative intervention if disease progresses 1. Triggers for intervention include Gleason score upgrade to ≥7 on repeat biopsy, PSA velocity >2.0 ng/mL/year, or increased tumor volume on biopsy (>3 cores positive or >50% involvement per core) 2.
Intermediate Risk Disease (Gleason 7)
Radical prostatectomy is a standard treatment option for patients with intermediate-risk disease and life expectancy >10 years 3. Benefits include complete removal of the prostate with accurate pathological staging, but potential complications include erectile dysfunction (up to 80%) and urinary incontinence (up to 49%) 4, 3.
External beam radiation therapy (EBRT) is equally effective, with a recommended minimum target dose of 70 Gy given in 2.0 Gy fractions 3. Neoadjuvant and concurrent ADT for 4-6 months should be considered for men with intermediate-risk disease receiving radical radiotherapy 4, 3.
Brachytherapy can be used as monotherapy for patients with low-intermediate risk (Gleason 3+4=7, PSA <10 ng/mL), though it should be used cautiously in patients with significant lower urinary tract symptoms as it can exacerbate urinary obstructive symptoms 3.
High Risk and Locally Advanced Disease
Options include external beam radiotherapy plus hormone treatment or radical prostatectomy plus pelvic lymphadenectomy 4. For men receiving radical radiotherapy for high-risk disease, neoadjuvant and concurrent ADT for 4-6 months are recommended, followed by adjuvant ADT for 2-3 years 4.
Primary ADT alone is not recommended as standard initial treatment for non-metastatic disease 4, 3.
Metastatic Disease Management
Continuous ADT is the recommended first-line treatment for metastatic hormone-naïve prostate cancer, achieved through bilateral orchiectomy (surgical castration) or LHRH agonists (medical castration) 1.
For patients fit enough for chemotherapy, adding docetaxel to ADT at initial diagnosis provides survival benefit, representing a paradigm shift from sequential therapy 1, 5. This combination improved median overall survival significantly compared to ADT alone 5.
Adding androgen receptor pathway inhibitors (such as abiraterone or darolutamide) to ADT improves survival 5. Abiraterone improved median overall survival from 36.5 months to 53.3 months (hazard ratio 0.66,95% CI 0.56-0.78) compared with medical castration alone 5.
Men starting ADT should be informed that regular exercise reduces fatigue and improves quality of life 4, 1.
Post-Treatment Management and Salvage Therapy
After radical prostatectomy, PSA should be undetectable (<0.2 ng/mL) within 2 months 1. Follow-up includes PSA measurement every 3 months during year 1, then every 6 months for 7 years 1.
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 4, 1.
Immediate post-operative radiotherapy after radical prostatectomy is not routinely recommended; patients with positive surgical margins or extra-capsular extension should be informed about the pros and cons of adjuvant radiotherapy 4.
Critical Pitfalls to Avoid
- Do not use cryotherapy, HIFU, or focal therapy as standard initial treatments for localized prostate cancer 1
- Do not initiate adjuvant radiotherapy immediately following radical prostatectomy, as it has not been shown to improve survival 3
- Do not use primary ADT alone as standard initial treatment for localized prostate cancer 4, 3
- Monitor patients on long-term ADT for osteoporosis and metabolic syndrome 1
- Recognize that brachytherapy can exacerbate urinary obstructive symptoms in patients with significant lower urinary tract symptoms 1, 3