Apalutamide-induced prostate-specific antigen response and its association with clinical outcomes in metastatic castration sensitive prostate cancer (Review).

Prostate-specific antigen (PSA) kinetics in metastatic castration-sensitive prostate cancer (mCSPC) have been evaluated as prognostic markers in relation to clinical outcomes under apalutamide plus androgen deprivation therapy (ADT). A literature search was conducted via PubMed, Scopus and Google Scholar. Randomized controlled trials, post hoc analyses, and real-world and retrospective cohort studies were included. Early and deep PSA responses (for example, PSA50, PSA90, PSA ≤0.2 ng/ml, ultralow PSA) were found to be induced more frequently and more rapidly when apalutamide + ADT were used. Such PSA responses at 3-6 months were correlated with prolonged radiographic progression-free survival, overall survival, and delayed progression to castration-resistant prostate cancer (CRPC). Comparative analyses demonstrated that PSA90 or ultralow PSA thresholds were reached sooner and in more patients with apalutamide than with abiraterone or enzalutamide, resulting in lower mortality at 24 months in real-world data. It is concluded that rapid, deep PSA suppression under apalutamide + ADT is associated with improved clinical outcomes in mCSPC. PSA response metrics are proposed to be considered as early surrogate endpoints for guiding treatment decisions but are recommended to be used in conjunction with imaging and clinical assessment.