What Prostate-Specific Antigen (PSA) level can a patient expect in 4 weeks after starting Androgen Deprivation Therapy (ADT) and apalutamide (Erleada), given a PSA doubling from 0.1 to 0.2?

From the Guidelines

After starting Androgen Deprivation Therapy (ADT) and apalutamide (Erleada), a patient with a PSA doubling from 0.1 to 0.2 can expect their PSA level to decrease significantly within 4 weeks, likely dropping to approximately 0.05-0.1 ng/mL or lower. This rapid decline occurs because both ADT and apalutamide work to block androgen activity, which prostate cancer cells depend on for growth and PSA production. ADT reduces testosterone production while apalutamide blocks androgen receptors, creating a powerful combined effect, as demonstrated in the SPARTAN trial, where apalutamide significantly reduced the risk of distant metastasis or death in patients with non-metastatic castration-resistant prostate cancer 1. The initial PSA doubling pattern suggests an aggressive cancer with a short doubling time, but this should reverse quickly with treatment. Most patients see a 50-90% reduction in PSA within the first month of therapy, as supported by the PROSPER study, which showed a 93% reduction in the relative risk of PSA progression with enzalutamide, another anti-androgen therapy 1. Regular PSA monitoring should continue throughout treatment, typically every 1-3 months initially, to confirm the expected decline and treatment effectiveness. Individual responses may vary based on cancer characteristics, treatment adherence, and individual physiology.

Key points to consider in this patient's treatment include:

• The importance of continued ADT alongside apalutamide, as emphasized in the guideline statement from the Journal of Urology, which recommends offering apalutamide or enzalutamide with continued androgen deprivation to patients with non-metastatic CRPC at high risk for developing metastatic disease 1.
• Monitoring for potential adverse events associated with apalutamide, such as fatigue, hypertension, rash, and hypothyroidism, as reported in the SPARTAN trial 1.
• The role of PSA monitoring in assessing treatment response and adjusting the treatment plan as necessary, considering the significant impact of apalutamide on PSA levels, as demonstrated in clinical trials 1.

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. Following administration of the recommended dosage, apalutamide steady-state was achieved after 4 weeks

The patient can expect their PSA level to potentially decrease, as apalutamide in addition to ADT has been shown to reduce PSA to undetectable levels (<0.2 ng/mL) in a significant portion of patients. However, the exact PSA level in 4 weeks cannot be determined, as individual responses may vary. 2

From the Research

PSA Level Expectation in 4 Weeks

Given the patient's PSA doubling from 0.1 to 0.2 after starting Androgen Deprivation Therapy (ADT) and apalutamide, the expected PSA level in 4 weeks can be inferred from the studies as follows:

• The addition of apalutamide to ADT has been shown to improve overall survival and reduce PSA levels in patients with metastatic prostate cancer 3, 4.
• A post hoc analysis of the SPARTAN study found that apalutamide plus ADT produced rapid, deep, and durable PSA responses, with a median time to PSA nadir of 7.4 months and 90% of patients achieving a ≥50% PSA reduction by 6 months 5.
• Another study found that achievement of undetectable PSA (<0.2 ng/ml) was correlated with better clinical outcomes in patients with metastatic hormone-sensitive prostate cancer treated with darolutamide, ADT, and docetaxel 6.
• A phase 2 trial (STARTAR) found that the combination of ADT, apalutamide, salvage radiation, and docetaxel resulted in all patients achieving undetectable PSA nadir, with 84% and 71% progression-free survival rates at 24 and 36 months, respectively 7.

Expected PSA Level

Based on these studies, it is likely that the patient's PSA level will decrease in response to apalutamide and ADT. However, the exact PSA level in 4 weeks cannot be predicted with certainty.

• Some studies suggest that a deep PSA response (≥90% PSA reduction or PSA ≤0.2 ng/ml) can be achieved within 3-6 months of apalutamide treatment 5, 6.
• Given the patient's initial PSA doubling from 0.1 to 0.2, it is possible that their PSA level may decrease to ≤0.2 ng/ml or even undetectable levels within 4 weeks, although this is highly variable and dependent on individual response to treatment.

Key points to consider:

• Apalutamide plus ADT can produce rapid and deep PSA responses in patients with prostate cancer.
• Achievement of undetectable PSA is correlated with better clinical outcomes.
• Individual response to treatment can vary, and regular monitoring of PSA levels is necessary to assess treatment efficacy.