What is the primary approach in managing high volume metastatic prostate cancer?

From the Guidelines

The primary approach in managing high volume metastatic prostate cancer is androgen deprivation therapy (ADT) combined with additional systemic treatments, with a strong recommendation for triplet therapy in patients who are fit for chemotherapy. ADT typically involves a GnRH agonist (such as leuprolide 7.5mg monthly or 22.5mg every 3 months) or antagonist (such as degarelix 240mg loading dose followed by 80mg monthly), often with an anti-androgen (such as bicalutamide 50mg daily) for the first 2-4 weeks to prevent testosterone flare. For high-volume disease, defined as visceral metastases or ≥4 bone lesions with at least one beyond the vertebral column and pelvis, ADT should be intensified by adding docetaxel chemotherapy (75mg/m² every 3 weeks for 6 cycles) and novel hormonal agents like abiraterone acetate (1000mg daily with prednisone 5mg daily) or enzalutamide (160mg daily) 1.

This intensification approach has demonstrated significant survival benefits of 10-15 months in clinical trials, with subgroup analysis showing that the survival benefit was more pronounced in patients with high-volume disease (HR, 0.63; 95% CI, 0.50–0.79; P,.001) 1. Treatment selection depends on patient factors including performance status, comorbidities, and potential side effect profiles. Bone-targeted agents such as zoledronic acid or denosumab should be considered for patients with bone metastases to reduce skeletal-related events. Regular monitoring of PSA levels, imaging, and assessment for treatment-related toxicities is essential for optimal management.

Some key points to consider in the management of high volume metastatic prostate cancer include:

• The use of ADT with treatment intensification is strongly recommended for patients with metastatic castration-sensitive prostate cancer 1
• Triplet therapy with ADT, docetaxel, and novel hormonal agents is a viable option for patients who are fit for chemotherapy 1
• The survival benefit of intensification therapy is more pronounced in patients with high-volume disease 1
• Patient factors, including performance status and comorbidities, should be taken into account when selecting treatment 1

From the FDA Drug Label

The primary efficacy outcome measure was radiographic progression-free survival (rPFS) based on blinded independent central review (BICR) Radiographic progression-free survival was defined as the time from randomization to radiographic disease progression at any time or death within 24 weeks after study drug discontinuation. High volume of disease is defined as metastases involving the viscera or, in the absence of visceral lesions, there must be 4 or more bone lesions, at least 1 of which must be in a bony structure beyond the vertebral column and pelvic bone XTANDI demonstrated a statistically significant improvement in rPFS and OS compared to placebo. Consistent rPFS results were observed in patients with high or low volume of disease and patients with and without prior docetaxel therapy

The primary approach in managing high volume metastatic prostate cancer is to use enzalutamide (XTANDI), which has demonstrated a statistically significant improvement in radiographic progression-free survival (rPFS) and overall survival (OS) compared to placebo.

• Key benefits of enzalutamide include:
  • Delay in time to radiographic disease progression
  • Delay in time to death
  • Improvement in overall survival
• Patient population: enzalutamide is effective in patients with high volume metastatic prostate cancer, regardless of prior docetaxel therapy 2.

From the Research

Primary Approach in Managing High Volume Metastatic Prostate Cancer

The primary approach in managing high volume metastatic prostate cancer involves combination systemic therapy, which is now the standard of care for all men with metastatic, hormone-sensitive prostate cancer (mHSPC) 3. This approach typically includes standard androgen deprivation therapy (ADT) and abiraterone acetate with prednisone or docetaxel (chemohormonal therapy), unless there are contraindications to combination therapy.

Effectiveness of Adding Octaves to ADT and Appliance

There is no direct evidence in the provided studies regarding the effectiveness of adding octaves to ADT and appliance in the case of high volume metastatic prostate cancer. However, studies suggest that combination therapy with ADT and other agents such as abiraterone acetate and prednisolone can improve overall survival and metastasis-free survival in men with high-risk non-metastatic prostate cancer 4.

Key Considerations

When managing high volume metastatic prostate cancer, key considerations include:

• Volume of disease burden
• Quality of life effects
• Duration of therapy
• Patient preferences for treatment
• The use of chemohormonal therapy or abiraterone and ADT, as there is no formally powered prospective head-to-head comparison of these options demonstrating superiority of one approach over the other 3

Treatment Options

Treatment options for high volume metastatic prostate cancer may include:

• Combination systemic therapy with ADT and abiraterone acetate with prednisone or docetaxel
• Chemohormonal therapy
• Abiraterone acetate and prednisolone with or without enzalutamide
• Radical prostatectomy in combination with optimal systemic therapy (currently being assessed in clinical trials)
• Metastasis-directed therapy with radiotherapy directed at metastatic lesions (still investigational) 3, 5