What does a decline in Prostate-Specific Antigen (PSA) from 0.2 to 0.17 in 30 days after starting Androgen Deprivation Therapy (ADT) plus apalutamide indicate?

From the Guidelines

A decline in PSA from 0.2 to 0.17 over 30 days after starting ADT plus apalutamide indicates an initial positive response to treatment, though the modest decrease suggests continued monitoring is necessary. This 15% reduction shows the therapy is likely working to suppress androgen activity and inhibit prostate cancer cell growth, as supported by the TITAN trial, which demonstrated that ADT plus apalutamide was associated with significantly longer rPFS (HR 0.48, CI: 0.39 to 0.60, P < .001) and OS (HR 0.67, CI: 0.51 to 0.89, P = .005) compared with placebo plus ADT 1. For optimal assessment, continued PSA monitoring every 1-3 months is recommended to establish a clear trend, as the full effect of ADT plus apalutamide may take 3-6 months to manifest. The combination therapy works by blocking testosterone production (ADT) while apalutamide prevents remaining androgens from binding to receptors in cancer cells.

Key Considerations

• The initial decline in PSA is encouraging, but PSA values should ideally decrease more substantially over time, potentially reaching undetectable levels in responsive disease.
• If PSA stabilizes or begins rising after this initial decline, treatment modification may be necessary after consultation with your oncologist.
• The TITAN trial results suggest that apalutamide plus ADT may be offered to men with metastatic noncastrate prostate cancer, including both those with de novo metastatic disease and those who have received prior therapy, such as RP or RT for localized disease 1.

Next Steps

• Continue PSA monitoring every 1-3 months to assess treatment response and adjust the treatment plan as needed.
• Regularly review the patient's overall clinical status, including any symptoms or side effects, to ensure the best possible outcomes.

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. A decline in Prostate-Specific Antigen (PSA) from 0.2 to 0.17 in 30 days after starting Androgen Deprivation Therapy (ADT) plus apalutamide may indicate a response to treatment, as the PSA level is approaching undetectable levels (<0.2 ng/mL). However, this decline is relatively small and more data is needed to determine the significance of this change. 2

From the Research

PSA Decline Indication

A decline in Prostate-Specific Antigen (PSA) from 0.2 to 0.17 in 30 days after starting Androgen Deprivation Therapy (ADT) plus apalutamide may indicate a positive response to treatment.

• The studies 3, 4, 5, 6, 7 suggest that a deep PSA decline is associated with improved clinical outcomes, including longer survival time and delayed progression of prostate cancer.
• According to the TITAN study 5, achievement of a deep PSA decline at landmark 3 months of apalutamide treatment was associated with longer overall survival, radiographic progression-free survival, time to PSA progression, and time to castration resistance.
• The SPARTAN study 4 also found that deep PSA responses were associated with improved time to PSA progression, metastasis-free survival, and overall survival.

Clinical Implications

The observed PSA decline may have several clinical implications:

• It may indicate that the treatment is effective in reducing the tumor burden and slowing down the progression of the disease 3, 5, 7.
• A deep PSA decline has been associated with improved health-related quality of life, including physical wellbeing 3.
• The association between PSA decline and clinical outcomes suggests that PSA measurements can be used to monitor disease evolution and tailor treatment approaches to improve PSA decline 7.

Limitations and Future Directions

While the available evidence suggests a positive association between PSA decline and clinical outcomes, there are some limitations to consider:

• The studies were conducted in specific patient populations, and the results may not be generalizable to all patients with prostate cancer.
• Further research is needed to fully understand the relationship between PSA decline and clinical outcomes, as well as to identify potential biomarkers for predicting treatment response.