Prostate-Specific Antigen Reduction After Androgen Receptor Pathway Inhibitor Initiation: Real-World Comparison of Disease Progression Among Patients With Metastatic Castration-Sensitive Prostate Cancer

Background: Prostate-specific antigen (PSA) has been used as both a screening tool and a marker for treatment response for advanced prostate cancer. With the introduction of androgen receptor pathway inhibitor (ARPI)-based treatment for metastatic castration-sensitive prostate cancer (mCSPC), there is a need to understand the impact that early treatment response, as measured by PSA, has on long-term clinical outcomes. Objectives: To assess whether long-term indicators of treatment success differ among ARPI-naïve patients with mCSPC who did or did not attain ≥90% reduction in PSA levels within 6 months of treatment initiation. Methods: Patients with mCSPC initiating a first ARPI (ie, apalutamide, enzalutamide, abiraterone acetate, darolutamide) were identified using electronic medical record data linked to insurance claims in the United States (1/1/2016–9/30/2022). Eligible patients were classified based on whether they achieved ≥90% reduction in PSA measured between pre-treatment and a window of 30 to 180 days after ARPI initiation. Cohorts were balanced using inverse probability of treatment weighting. Weighted Kaplan-Meier analysis was used to compare overall survival and castration-resistance–free survival by 36 months post-index between those with and without ≥90% PSA reduction. Results: Weighted cohorts included 1192 patients with early PSA reduction ≥90% and 699 without. By 36 months, significantly better overall survival was observed in those with early PSA reduction ≥90% than in those without (71.5% vs 54.7%; hazard ratio [HR]: 0.40, 95% confidence interval [CI]: 0.31, 0.50; P<.001). Similarly, significantly better castration-resistance–free survival was observed in those with early PSA reduction ≥90% than in those without (53.3% vs 36.8%; HR: 0.51, 95% CI: 0.43, 0.60; P< .001). Discussion: Early reduction of PSA levels by ≥90% within 6 months of ARPI initiation among patients with mCSPC in the real world is a robust indicator of treatment success, with improved long-term clinical outcomes, including survival and reduction in disease progression. Conclusions: These findings corroborate those of clinical trials and highlight the long-term benefits of an early and deep PSA response to ARPIs among real-world patients with mCSPC in the United States.