What is the best treatment approach for a patient with high-volume metastatic prostate cancer and biochemical recurrence?

From the Guidelines

For a 79-year-old patient with high-volume metastatic prostate cancer and biochemical recurrence, the recommended treatment approach is androgen deprivation therapy (ADT) combined with either docetaxel chemotherapy or novel hormonal agents, as outlined in the most recent guidelines 1. The patient's age and general good health should be considered when selecting a treatment regimen.

• A typical regimen includes a GnRH agonist/antagonist (such as leuprolide 22.5 mg every 3 months or degarelix 240 mg loading dose followed by 80 mg monthly) plus docetaxel 75 mg/m² every 3 weeks for 6 cycles.
• Alternatively, ADT can be combined with abiraterone acetate (1000 mg daily with prednisone 5 mg daily), enzalutamide (160 mg daily), or apalutamide (240 mg daily). The addition of docetaxel or novel hormonal therapy to ADT has shown significant survival benefits for patients with high-volume disease, as defined by visceral metastases or ≥4 bone lesions with ≥1 beyond vertebrae/pelvis 1. Treatment selection should consider the patient's performance status, comorbidities, and potential side effects, with docetaxel preferred for patients who can tolerate chemotherapy and need rapid disease control, and hormonal agents for those with significant comorbidities 1. This intensified approach targets both androgen-dependent and independent cancer cell populations, providing more comprehensive disease control than ADT alone, which explains the improved survival outcomes observed in clinical trials 1.

From the FDA Drug Label

XTANDI is an androgen receptor inhibitor indicated for the treatment of patients with: • castration-resistant prostate cancer. (1) • metastatic castration-sensitive prostate cancer. (1) • non‑metastatic castration‑sensitive prostate cancer with biochemical recurrence at high risk for metastasis (1)

The best treatment approach for a patient with high-volume metastatic prostate cancer and biochemical recurrence is to consider enzalutamide (XTANDI) as a treatment option.

• The patient should receive 160 mg of XTANDI administered orally once daily with or without food.
• Additionally, the patient should also receive a gonadotropin-releasing hormone (GnRH) analog concurrently or should have had bilateral orchiectomy 2.

From the Research

Treatment Approach for High-Volume Metastatic Prostate Cancer

The treatment approach for a patient with high-volume metastatic prostate cancer and biochemical recurrence involves several considerations.

• The patient's age and overall health should be taken into account when deciding on a treatment plan.
• Androgen deprivation therapy (ADT) has been a cornerstone in the treatment of prostate cancer, particularly in the metastatic setting 3.
• The choice of ADT depends on various factors, including cost, availability, ease of administration, and patient preference 3.

Role of ADT in Biochemical Recurrence

In the case of biochemical recurrence, ADT can be considered, especially for patients at high risk 4.

• The type of ADT to be used in biochemical recurrence is still a topic of debate, with options ranging from oral-only peripheral blockade to complete hormonal therapy 4.
• Intermittent hormonal therapy (IHT) has shown promise in this setting, with good randomized controlled trial support 4.

Gonadotropin-Releasing Hormone Agonists

Gonadotropin-releasing hormone agonists (GnRH-A) are a type of ADT that can be used in the treatment of prostate cancer.

• All GnRH-A have comparable potential to suppress testosterone levels, although goserelin has shown better efficacy in maintaining testosterone levels ≤50 ng/dL compared with leuprolide 5.
• The choice of GnRH-A should be based on a holistic approach, considering the patient's profile and disease characteristics 5.

Management of Biochemical Recurrence

The management of biochemical recurrence after primary curative treatment for prostate cancer is a complex issue.

• Adjuvant therapy, such as radiation therapy or ADT, can be considered for patients at high risk of progression 6.
• Salvage therapy, including radiation therapy, surgery, or ADT, can be considered for patients with biochemical recurrence after primary treatment 6.

Novel Therapies

Novel therapies, such as darolutamide, have shown promise in the treatment of high-volume metastatic prostate cancer.

• The addition of darolutamide to ADT and docetaxel has been shown to improve overall survival and prostate-specific antigen (PSA) responses in patients with metastatic hormone-sensitive prostate cancer 7.
• The achievement of undetectable PSA (<0.2 ng/ml) has been correlated with better clinical outcomes, including longer overall survival and delayed time to castration-resistant prostate cancer 7.