PSA Absolute Value Versus PSA Response Rate: Which Is More Valuable for Estimating Survival Outcomes With ARPI Treatment for Metastatic Hormone-Sensitive Prostate Cancer (mHSPC) in Real-World Analyses?

Introduction: Prostate-specific antigen (PSA) kinetics serve as valuable surrogate markers for estimating survival outcomes in metastatic hormone-sensitive prostate cancer (mHSPC) treated with androgen receptor pathway inhibitors (ARPI). While both the PSA response rate and absolute PSA value are typically assessed, determining which marker holds greater significance in real-world clinical settings is a critical clinical question. In this study, we compare the PSA response rate and absolute PSA value 3 months after the initiation of doublet ARPI therapy to identify which serves as a more effective surrogate marker in practice.

Patients And Methods: A total of 273 patients with mHSPC treated with ARPIs such as abiraterone acetate, enzalutamide, or apalutamide between February 2018 and June 2023 were included in this study. The study investigated PSA kinetics, including PSA levels at 3 months and the PSA response rate at 3 months. The outcome measures assessed were castration-resistant prostate cancer-free survival (CRPCFS), cancer-specific survival (CSS), and overall survival (OS).

Results: The Youden index for the absolute PSA value at 3 months is 0.740 ng/mL. There is a significant difference in survival outcomes (CRPCFS, CSS, and OS) between patients with PSA levels > 0.740 ng/mL and those with ≤ 0.740 ng/mL. Additionally, the Youden index for the PSA response rate at 3 months is -99.80%. There is also a significant difference in survival outcomes (CRPCFS, CSS, and OS) between patients with response rates > -99.80% and those with rates ≤ -99.80%. In terms of clinical demographics with or without achieving PSA absolute value ≦ 0.740 ng/mL and PSA response rate ≦ -99.8%, although almost factors are different significantly (iPSA, age, PS, LN metastasis, EOD, CHAARTED criteria, LATTITUDE criteria, Hb, ALP, and LDH) between > 0.740 ng/mL and ≦ 0.740 ng/mL cohort, there are no significant difference in clinical factors other than age between > -99.80% and ≦ -99.80% cohort.

Conclusion: Both the absolute value of PSA and the PSA response rate at 3 months after the initiation of ARPI can estimate survival outcomes. However, the PSA response rate is a more valuable surrogate marker for assessing treatment efficacy than the absolute PSA value. This is because the baseline clinical factors differ significantly among cohorts categorized by absolute PSA values, allowing for better predictions of survival outcomes at the start of treatment. Findings of this study could aid in decision-making following the initiation of doublet ARPI therapy within a short timeframe. Further studies are needed to validate our results.