What is the optimal treatment plan for a patient with high-volume metastatic prostate cancer and declining PSA levels after starting ADT and apalutamide?

From the Guidelines

For a patient with high-volume metastatic prostate cancer showing declining PSA levels after starting androgen deprivation therapy (ADT) and apalutamide, the optimal treatment plan should continue the current regimen while adding docetaxel chemotherapy. The recommended approach is to maintain ADT (typically a GnRH agonist/antagonist) plus apalutamide (240mg daily) and add docetaxel 75mg/m² intravenously every 3 weeks for 6 cycles, as supported by the high-quality evidence from the ENZAMET and TITAN trials 1. Regular monitoring should include PSA measurements every 3 months, imaging assessments every 3-6 months, and vigilant monitoring for side effects. The declining PSA indicates treatment response, but intensification with chemotherapy is still beneficial in high-volume disease, as shown in the CHAARTED trial 1. This triplet therapy approach (ADT + novel hormonal agent + docetaxel) has demonstrated superior outcomes in high-volume metastatic disease by targeting androgen signaling through multiple mechanisms while also providing non-hormonal cytotoxic effects. After completing docetaxel, the patient should continue ADT and apalutamide until disease progression. Bone-targeted therapy with zoledronic acid or denosumab should be considered if bone metastases are present, along with calcium and vitamin D supplementation to prevent skeletal-related events. Key considerations in this treatment plan include:

• The patient's high-volume metastatic disease, which benefits from the addition of docetaxel to ADT and apalutamide
• The importance of regular monitoring to assess treatment response and potential side effects
• The need for bone-targeted therapy to prevent skeletal-related events in patients with bone metastases
• The high-quality evidence supporting the use of this triplet therapy approach in high-volume metastatic prostate cancer, as demonstrated in the ENZAMET and TITAN trials 1 and the CHAARTED trial 1.

From the FDA Drug Label

Patients were required to have a PSADT ≤ 10 months and confirmation of non-metastatic disease by blinded independent central review (BICR). The major efficacy outcome measure of the study was metastasis-free survival (MFS), defined as the time from randomization to the time of first evidence of BICR-confirmed distant metastasis, defined as new bone or soft tissue lesions or enlarged lymph nodes above the iliac bifurcation, or death due to any cause, whichever occurred first A statistically significant improvement in MFS and OS was demonstrated in patients randomized to receive ERLEADA compared with patients randomized to receive placebo.

The patient has high-volume metastatic prostate cancer and has recently started ADT and apalutamide. The PSA doubling time is not explicitly stated to be ≤ 10 months, and the patient has metastatic disease, which is not consistent with the patient population in the study.

• The patient's PSA levels have declined after starting treatment.
• The patient has had a PSMA Pet scan showing high-volume metastasis. Given the patient's metastatic disease and high-volume metastasis, the treatment plan should be focused on controlling the disease and managing symptoms. However, the FDA drug label for apalutamide does not directly address the treatment of patients with high-volume metastatic prostate cancer. Key considerations for the treatment plan include:
• Continuing ADT and apalutamide if tolerated, as the patient has had a decline in PSA levels.
• Monitoring for disease progression and adjusting treatment as needed.
• Managing symptoms and improving quality of life. It is essential to consult with a healthcare professional to determine the best course of treatment for this patient, as the FDA drug label does not provide direct guidance for this specific scenario 2.

From the Research

Treatment Plan for High-Volume Metastatic Prostate Cancer

The patient's recent PSMA Pet scan showed high-volume metastasis, and they have been experiencing a decline in PSA levels after starting ADT and apalutamide. The optimal treatment plan for this patient can be informed by the following considerations:

• The TITAN study 3, 4 demonstrated that apalutamide plus ADT increased the length of time that participants remained alive compared with placebo plus ADT, and that a deep PSA decline in response to treatment was associated with longer survival time and improved outcomes.
• The SPARTAN study 5 found that apalutamide plus ADT produced rapid, deep, and durable PSA responses, which were associated with improved clinical outcomes, including longer survival.
• The use of PSMA PET imaging 6 can help identify patients with high-volume disease and inform treatment decisions.
• For patients with oligorecurrent prostate cancer, metastasis-directed radiotherapy (MDT) with concurrent androgen deprivation therapy (ADT) may improve biochemical progression-free survival (bRFS) 7.

Key Considerations

• The patient's PSA decline after starting ADT and apalutamide suggests a positive response to treatment.
• The high-volume metastasis identified on the PSMA Pet scan indicates a more advanced disease state.
• The treatment plan should take into account the patient's overall health, disease characteristics, and treatment goals.

Potential Treatment Options

• Continue ADT and apalutamide, with regular monitoring of PSA levels and imaging studies to assess disease response.
• Consider adding other therapies, such as MDT or chemotherapy, to the treatment plan if the disease progresses or if the patient experiences a decline in PSA levels.
• Discuss the potential benefits and risks of each treatment option with the patient, and involve them in the decision-making process.