Treatment of 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) as the foundation of treatment. 1
Risk Stratification and Staging
Risk stratification is essential before selecting treatment, as it determines prognosis and guides therapeutic decisions 1:
- Very low risk: Gleason score ≤6, PSA <10 ng/mL, <3 positive biopsy cores with ≤50% cancer per core, PSA density <0.15 ng/mL/g 1
- Low risk: Gleason score ≤6 and PSA <10 ng/mL 1
- Intermediate risk: Gleason score 7, or PSA 10-20 ng/mL 1
- High risk: Gleason score 8-10, or PSA >20 ng/mL 1
- Very high risk/locally advanced: T3b-T4 disease 1
Staging workup for intermediate and high-risk disease should include bone scintigraphy and cross-sectional imaging (CT or MRI) to evaluate for metastases 2. Nodal staging can be performed with CT, MRI, choline PET/CT, or pelvic lymph node dissection 2.
Treatment by Risk Category
Very Low and Low Risk Disease
For patients with very low or low risk disease and life expectancy <10 years, observation (watchful waiting) is the recommended approach 1. This involves monitoring without immediate curative intent, with delayed hormone therapy if symptomatic progression occurs 2.
For patients with life expectancy ≥10 years, active surveillance is the preferred option 1. Active surveillance protocol includes 1:
- PSA measurement every 6 months
- Digital rectal examination every 12 months
- Repeat prostate biopsy every 12 months
Alternative curative options include radical prostatectomy, external beam radiation therapy (EBRT), or brachytherapy 1. However, active surveillance avoids treatment-related morbidity while maintaining the option for curative intervention if disease progresses 2.
Intermediate Risk Disease
For intermediate risk disease with life expectancy ≥10 years, treatment options include radical prostatectomy with pelvic lymph node dissection, EBRT with or without short-term ADT (4-6 months), or brachytherapy 1. The choice depends on patient preference, comorbidities, and tolerance for treatment-related adverse effects 2.
Neoadjuvant and concurrent ADT for 4-6 months should be considered when using EBRT for intermediate-risk disease 2. EBRT should utilize conformal techniques with a minimum target dose of 70 Gy in 2.0 Gy fractions or equivalent 1.
High Risk and Locally Advanced Disease
For high-risk disease with life expectancy ≥5 years, standard treatment is EBRT plus long-term ADT for 2-3 years 2, 1. This combination improves survival compared to radiation alone 2.
Alternative options for highly selected high-risk patients include radical prostatectomy with extended pelvic lymph node dissection 2. However, surgery alone is generally insufficient for high-risk disease without additional therapy 1.
Primary ADT alone should not be used as standard initial treatment for non-metastatic disease, as it does not improve survival 2, 1.
Metastatic Disease
Hormone-Sensitive Metastatic Disease
Continuous ADT is the recommended first-line treatment for metastatic hormone-naïve prostate cancer 2, 3. ADT can be achieved through 2, 3:
- Bilateral orchiectomy (surgical castration)
- LHRH agonists (medical castration) such as goserelin 4
When initiating LHRH agonist therapy, an antiandrogen should be administered for 3-4 weeks to prevent testosterone flare 3.
For patients fit enough for chemotherapy, adding docetaxel to ADT at initial diagnosis provides survival benefit 2, 3. This represents a paradigm shift from sequential therapy and should be strongly considered in appropriate candidates 5.
Combined androgen blockade (adding an antiandrogen to castration) may provide a small survival benefit but increases toxicity 2, 3. The 2007 ASCO guideline states CAB should be considered, though the benefit is modest 2. More recent guidelines suggest first-line management can be based on castration alone given the minimal survival benefit and added cost and toxicity of antiandrogens 2.
Castration-Resistant Prostate Cancer (CRPC)
When disease progresses despite castrate testosterone levels, patients should continue androgen suppression and receive additional therapies 2:
For asymptomatic or mildly symptomatic chemotherapy-naïve metastatic CRPC, abiraterone or enzalutamide are recommended first-line agents 2, 6. Abiraterone inhibits CYP17, blocking androgen biosynthesis in the testes, adrenals, and tumor tissue 6.
For symptomatic metastatic CRPC, docetaxel chemotherapy is recommended 2. Docetaxel has demonstrated improved overall survival of 2-2.5 months and quality of life benefits 7.
For bone-predominant symptomatic metastatic CRPC without visceral metastases, radium-223 is recommended 2.
Post-Treatment Management
After Radical Prostatectomy
PSA should be undetectable (<0.2 ng/mL) within 2 months after surgery 1. Follow-up includes 2:
- PSA measurement every 3 months during year 1, then every 6 months for 7 years
- Digital rectal examination is optional if PSA remains undetectable
For biochemical recurrence (rising PSA), salvage radiation therapy to the prostate bed should be initiated early (PSA <0.5 ng/mL) 2, 1. Early salvage radiation improves outcomes compared to delayed treatment 2.
Adjuvant radiation therapy immediately after surgery is not routinely recommended but should be discussed with patients who have positive surgical margins or extracapsular extension 2.
After Radiation Therapy
PSA should reach ≤1 ng/mL within 16 months after EBRT 1. Follow-up includes 2:
- PSA measurement and digital rectal examination every 6 months indefinitely
For biochemical recurrence after radiation, intermittent ADT is recommended over continuous ADT, as it provides quality of life benefits without compromising efficacy 2.
Important Caveats and Pitfalls
Avoid these common errors:
- Do not use cryotherapy, HIFU, or focal therapy as standard initial treatments for localized prostate cancer—these lack sufficient evidence 1
- Do not rely solely on PSA for monitoring in patients with neuroendocrine features, as PSA may not reflect disease activity 3
- Recognize that brachytherapy can exacerbate urinary obstructive symptoms; patients with baseline obstruction may be better candidates for surgery 1
- Inform patients that ADT combined with radiation increases adverse effects on sexual function compared to radiation alone 1
- Monitor men on long-term ADT for osteoporosis and metabolic syndrome 3
- Recommend regular exercise to all men on ADT, as it reduces fatigue and improves quality of life 2, 3
Treatment-related morbidity differs significantly between modalities: Radical prostatectomy causes higher rates of urinary incontinence and erectile dysfunction, particularly in older men, while radiation therapy has different toxicity profiles including bowel symptoms 1, 8.