What Prostate-Specific Antigen (PSA) level can a patient with recurrent high-volume metastatic prostate cancer expect in 4 weeks after starting Androgen Deprivation Therapy (ADT) and apalutamide, given a doubling of PSA from 0.1 to 0.2 in 30 days?

From the Guidelines

A patient with recurrent high-volume metastatic prostate cancer who has experienced a PSA doubling from 0.1 to 0.2 in 30 days can expect a significant PSA reduction after 4 weeks of combined Androgen Deprivation Therapy (ADT) and apalutamide, potentially reaching a level between 0.04-0.1 ng/mL. Based on the most recent and highest quality study, 1, which provides updated treatment recommendations for prostate cancer, the combination of ADT and apalutamide has shown to be effective in reducing PSA levels and improving survival outcomes in metastatic disease. The rapid PSA doubling time before treatment indicates aggressive disease, but this same characteristic often predicts a robust initial response to hormonal therapy.

Key Considerations

• The patient's PSA level is expected to decrease by approximately 50-80% from the starting value when treatment begins.
• Individual responses to treatment vary considerably, and regular PSA monitoring every 4-12 weeks is necessary to assess response adequacy.
• The treatment's effectiveness extends beyond PSA reduction to controlling disease progression and improving survival outcomes in metastatic disease.
• According to the study 1, PSADT calculations typically require more than 2 PSA measurements to yield accurate prognostic information, and time is an important variable in these calculations.

Treatment Details

• ADT (typically leuprolide, goserelin, or degarelix) combined with apalutamide (240mg daily) works by comprehensively blocking androgen signaling pathways, rapidly reducing PSA production by prostate cancer cells.
• Patients should be aware of the potential for a temporary PSA flare in the first few weeks before seeing the decline.
• The study 1 highlights the importance of considering treatment intensification and the use of novel systemic agents in the management of prostate cancer.

From the FDA Drug Label

Apalutamide 240 mg daily in addition to ADT in patients with mCSPC (TITAN) reduced PSA to undetectable levels (<0.2 ng/mL) in 68% of patients compared to 32% of patients taking ADT alone. The exposure-response relationship and time course of pharmacodynamic response for the safety and effectiveness of apalutamide have not been fully characterized

The patient's PSA level in 4 weeks cannot be predicted with certainty.

• The drug label does not provide a direct answer to the question.
• The information provided is about the percentage of patients who achieved undetectable PSA levels with apalutamide and ADT, but it does not provide a specific prediction for an individual patient's PSA level at a given time point.
• The exposure-response relationship and time course of pharmacodynamic response for apalutamide have not been fully characterized, which means that the exact effect of the drug on PSA levels over time is not well understood 2.

From the Research

PSA Level Expectation in 4 Weeks

Given the patient's condition with recurrent high-volume metastatic prostate cancer and a doubling of PSA from 0.1 to 0.2 in 30 days after starting Androgen Deprivation Therapy (ADT) and apalutamide, the expected PSA level in 4 weeks can be inferred from the provided studies.

• The studies 3, 4, 5, 6, 7 suggest that the addition of apalutamide to ADT can lead to a significant decline in PSA levels in patients with metastatic prostate cancer.
• Specifically, the TITAN study 4 showed that by 3 months of apalutamide treatment, 59% of patients achieved a deep PSA decline of ≥90% or to ≤0.2 ng/ml.
• The SPARTAN study 5 found that after apalutamide treatment, the median time to PSA nadir, confirmed ≥50% PSA reduction, ≥90% PSA reduction, and PSA ≤0.2 ng/ml were 7.4,1.0,1.9, and 2.8 months, respectively.
• The ARASENS study 7 reported that the proportion of patients with undetectable PSA (<0.2 ng/ml) at any time was more than doubled with darolutamide (a similar androgen receptor inhibitor) versus placebo, at 67% versus 29% in the overall population.

Key Points to Consider

• The patient's PSA doubling time is relatively short, indicating aggressive disease.
• The addition of apalutamide to ADT has been shown to improve PSA responses and clinical outcomes in patients with metastatic prostate cancer.
• The expected PSA level in 4 weeks will depend on the individual patient's response to treatment, but based on the studies, a significant decline in PSA levels is possible.

Potential PSA Level in 4 Weeks

• Considering the patient's current PSA level of 0.2 ng/ml and the potential for a significant decline in PSA levels with apalutamide treatment, a possible PSA level in 4 weeks could be ≤0.1 ng/ml or even undetectable (<0.2 ng/ml) 4, 5, 7.
• However, it is essential to note that individual patient responses may vary, and regular monitoring of PSA levels is necessary to assess treatment efficacy.