How long before Androgen Deprivation Therapy (ADT) and apalutamide start to reduce Prostate-Specific Antigen (PSA) levels?

From the Guidelines

Androgen Deprivation Therapy (ADT) and apalutamide typically begin reducing PSA levels within 2-4 weeks after starting treatment, with significant decreases often observed by the first follow-up appointment at 4-6 weeks. This is based on the most recent and highest quality study available, which demonstrates the efficacy of this combination therapy in reducing PSA levels and improving clinical outcomes 1. The mechanism of action involves ADT lowering testosterone levels, while apalutamide blocks androgen receptors, disrupting the mechanisms that fuel prostate cancer growth.

The study published in 2023, which is the most recent and highest quality evidence available, supports the use of apalutamide with ADT in reducing PSA levels and improving overall survival 1. The TITAN study, referenced in this publication, demonstrated a significant improvement in median overall survival with the combination of apalutamide and ADT compared to ADT alone.

Key points to consider when using ADT and apalutamide include:

• Regular PSA monitoring is essential during treatment, typically every 1-3 months initially, then potentially less frequently once levels stabilize.
• Patients should continue taking these medications as prescribed even after seeing PSA improvements, as interrupting treatment can lead to rapid PSA increases and disease progression.
• The combination of ADT (such as leuprolide or goserelin) with apalutamide provides more complete androgen blockade than ADT alone, which explains its effectiveness in reducing PSA levels and improving clinical outcomes.
• The rate and extent of PSA decline can vary between individuals based on factors such as disease burden, prior treatments, and individual biology.

Overall, the combination of ADT and apalutamide is a highly effective treatment strategy for reducing PSA levels and improving clinical outcomes in patients with prostate cancer, as supported by the most recent and highest quality evidence available 1.

From the Research

Time to PSA Reduction with ADT and Apalutamide

• The time to PSA reduction with Androgen Deprivation Therapy (ADT) and apalutamide can vary, but studies have shown that significant reductions can occur within a few months of treatment 2, 3, 4.
• By 3 months, PSA levels decreased in most apalutamide-treated patients, with a median time to PSA nadir of 7.4 months 2.
• A study found that 90% of apalutamide patients had a ≥50% PSA reduction, 57% had a ≥90% PSA reduction, and 32% had a PSA ≤0.2 ng/ml by 6 months 2.
• Another study reported that apalutamide plus ADT achieved a lower median nadir PSA (0.02 ng/mL) and a shorter mean time to nadir (4.5 months) compared to abiraterone plus ADT 4.

Factors Influencing PSA Reduction

• The depth of PSA decline was associated with improved clinical outcomes, including longer overall survival and delayed disease progression 2, 3, 4.
• Achieving a PSA level of ≤0.2 ng/ml was associated with improved time to PSA progression, metastasis-free survival, and overall survival 2.
• A study found that patients who achieved a PSA level of ≤0.02 ng/ml had a significantly delayed progression (HR 0.07,95% CI 0.02-0.28; p < 0.001) 4.

Comparison with Other Treatments

• Apalutamide plus ADT was compared to abiraterone plus ADT in a study, which found that apalutamide achieved deeper and more sustained PSA reductions, translating into delayed disease progression 4.
• Another study compared apalutamide plus ADT to apalutamide monotherapy and ADT monotherapy, and found that the combination of apalutamide and ADT prolonged time to PSA progression, although this change did not reach statistical significance 5.