What are the treatment options for a patient with very high risk prostate cancer?

Treatment of Very High-Risk Prostate Cancer

For patients with very high-risk prostate cancer (clinical stage T3b-T4), the preferred treatment is radiation therapy combined with long-term androgen deprivation therapy (ADT) for 2-3 years (Category 1 recommendation). 1

Definition of Very High-Risk Disease

Very high-risk prostate cancer is defined as:

• Clinical stage T3b-T4 (locally advanced disease with fixation or invasion of adjacent structures) 1, 2
• This classification is independent of PSA level or Gleason score 3

Primary Treatment Options

First-Line: Radiation Therapy + Long-Term ADT (Preferred)

External beam radiation therapy (EBRT) combined with long-term ADT (typically 2-3 years) is the Category 1 preferred treatment for very high-risk disease. 1

• Radiation dose should be >70 Gy using conformal techniques 1, 2
• ADT duration should be long-term (2-3 years minimum) for this risk category 1
• This combination has demonstrated survival benefit over radiation alone in randomized controlled trials 1
• ADT can be achieved through medical castration with LHRH agonists (such as goserelin 10.8 mg subcutaneously every 12 weeks) or surgical castration 4, 5

Alternative Option: EBRT + Brachytherapy

Combination of EBRT plus brachytherapy with or without long-term ADT is another primary treatment option. 1

• This approach provides dose escalation to the prostate
• The optimal duration of ADT in this setting remains unclear 1

Selected Surgical Candidates

Radical prostatectomy with pelvic lymph node dissection (PLND) may be considered in highly selected patients with no fixation to adjacent organs. 1

• Surgery is emerging as an option in the very high-risk setting when combined with adjuvant radiation/ADT 3
• Radical prostatectomy offers potential benefits including: avoiding long-term ADT toxicity, reducing symptomatic local recurrence, enabling complete pathological staging, and potentially reducing late adverse effects like secondary malignancy 6
• However, this approach requires careful patient selection and typically necessitates multimodal therapy 6, 3

Palliative ADT Alone

ADT alone is reserved only for patients not eligible for definitive therapy due to comorbidities or limited life expectancy. 1

• ADT alone is insufficient as primary treatment for patients who are candidates for curative therapy 1

Critical Treatment Principles

What NOT to Do

• Never use ADT alone as primary treatment in patients eligible for definitive therapy - it does not improve survival compared to combined modality treatment 1, 2
• Do not use cryotherapy, HIFU, or focal therapy as standard initial treatments - insufficient long-term data 1, 2, 4
• Avoid brachytherapy monotherapy in very high-risk disease - inadequate for this risk category 1

Multimodal Approach Considerations

Growing evidence suggests neoadjuvant taxane-based chemotherapy may be beneficial in the context of a multimodal approach for very high-risk disease. 3

• This represents an evolving area where the optimal therapy continues to be refined 3

Follow-Up After Treatment

Post-treatment monitoring should include PSA measurement every 6-12 months for the first 5 years, then annually. 1, 2

• After EBRT, PSA should reach ≤1 ng/mL within 16 months 2, 4
• First follow-up visit at 3 months should include PSA measurement, digital rectal examination, and assessment of treatment-related symptoms 2

Managing ADT Toxicity

Patients on long-term ADT require monitoring for osteoporosis and metabolic syndrome. 4

• Regular exercise should be recommended to all men on ADT to reduce fatigue and improve quality of life 4
• Patients should be informed that ADT with radiation increases adverse effects on sexual function 2

Common Pitfalls to Avoid

• Undertreatment with radiation alone - always combine with long-term ADT for very high-risk disease 1
• Insufficient ADT duration - ensure 2-3 years minimum, not the shorter 4-6 month courses used for intermediate-risk disease 1
• Inappropriate patient selection for surgery - only consider in patients without fixation to adjacent organs 1
• Failure to use pelvic lymph node dissection when performing radical prostatectomy in this population 1, 2