Prostate Cancer Treatment: A Risk-Stratified Approach
For prostate cancer treatment, the approach should be based on risk stratification, with radical prostatectomy or radiotherapy plus androgen deprivation therapy (ADT) recommended for localized disease, and ADT plus docetaxel or novel hormonal agents for metastatic disease.
Risk Assessment and Classification
Prostate cancer treatment decisions should be guided by risk classification:
- Low-risk disease: T1-2a, Gleason score ≤6, PSA <10 ng/mL 1
- Intermediate-risk disease: T2b-T2c, Gleason score 7, PSA 10-20 ng/mL 1
- High-risk disease: T3-T4, Gleason score 8-10, PSA >20 ng/mL 1
Treatment by Disease Stage
Localized Disease
Low-risk disease:
Intermediate-risk disease:
- For patients with life expectancy <10 years: observation or radical prostatectomy or EBRT (with or without brachytherapy; with or without hormone therapy for 4-6 months) 1
- For patients with life expectancy ≥10 years: radical prostatectomy or EBRT (with or without brachytherapy; with or without hormone therapy for 4-6 months) 1
High-risk disease:
Locally Advanced Disease
- External beam radiotherapy plus hormone treatment for at least 2 years is recommended 1
- Radical prostatectomy plus extended lymphadenectomy can be considered in highly selected cases 1
Metastatic Disease
Hormone-sensitive metastatic disease:
Castration-resistant prostate cancer (CRPC):
- Abiraterone or enzalutamide for asymptomatic/mildly symptomatic patients 1, 2
- Docetaxel (75 mg/m² every 3 weeks with prednisone 5 mg twice daily) for symptomatic patients 2, 3
- For bone-predominant disease without visceral metastases, Radium-223 should be considered 1, 2
- Post-docetaxel options: cabazitaxel, abiraterone, enzalutamide (if not used previously), or Radium-223 (for those without visceral metastases) 2
Special Considerations
Neoadjuvant and Adjuvant Therapy
- Neoadjuvant LHRH agonist therapy for 4-6 months is recommended for men receiving radical RT for high-risk disease 1
- Adjuvant hormonal therapy for 2-3 years is recommended for men receiving neoadjuvant hormonal therapy and radical RT who are at high risk of prostate cancer mortality 1
Treatment of Relapse After Radical Therapy
- Following radical prostatectomy, salvage RT to the prostate bed is recommended for PSA failure (ideally when PSA <0.5 ng/ml) 1
- Early ADT is not routinely recommended for men with biochemical relapse unless they have symptomatic local disease, proven metastases, or PSA doubling time <3 months 1
Monitoring and Side Effect Management
- Regular PSA monitoring is essential after treatment
- For patients on ADT, regular exercise should be recommended to reduce fatigue and improve quality of life 1, 2
- Monitor for and manage common side effects of hormonal therapy: hot flashes, sexual dysfunction, bone density loss, metabolic changes
- For patients receiving docetaxel, monitor for neutropenia, hypersensitivity reactions, and fluid retention 3
Important Caveats
Avoid docetaxel in patients with liver dysfunction (bilirubin > ULN, or AST/ALT >1.5 × ULN with alkaline phosphatase >2.5 × ULN) due to increased risk of severe toxicity 3
Monitor blood counts during chemotherapy as neutropenia may be severe and result in infection 3
Consider comorbidity-adjusted life expectancy when making treatment decisions, as this significantly impacts the risk-benefit ratio of aggressive treatments 1
Patients with neuroendocrine features should preferentially receive chemotherapy rather than hormonal therapy 2
For bone metastases at risk for skeletal-related events, consider denosumab or zoledronic acid 2
The treatment landscape for prostate cancer continues to evolve, with newer agents showing improved survival outcomes, particularly in the metastatic setting. The integration of these therapies into clinical practice requires careful consideration of disease characteristics, patient factors, and potential side effects.