This retrospective cohort study used Veterans Health Administration data (2006–2024, index dates 2018–2023) to compare two PSA-response metrics — PSA nadir <0.2 ng/mL vs. ≥90% PSA decline within 9 months of ADT initiation — and their association with overall survival (OS) and disease progression in 4,890 men with mCSPC receiving ADT ± ARPIs, NSAAs, or docetaxel.
Achieving PSA <0.2 ng/mL within 9 months was associated with a 54% lower risk of death (adjusted HR 0.46; 95% CI 0.40–0.54) and a 55% lower risk of disease progression (adjusted HR 0.45; 95% CI 0.40–0.50) vs. not achieving it; 3-year OS was ~78–83% vs. ~48–51%. In contrast, ≥90% PSA decline alone (without reaching <0.2 ng/mL) was not associated with improved OS or disease progression. ADT + ARPI nearly doubled the rate of achieving PSA <0.2 ng/mL vs. ADT alone (OR 2.36; 95% CI 1.97–2.83).
- Retrospective VHA cohort; findings may not generalize beyond a predominantly older male veteran population. - Key confounders (tumor grade, disease volume) were unavailable in the administrative dataset. - Testosterone levels were not used to define castration sensitivity, and administrative coding inaccuracies may affect cohort classification.
Clinicians should target a PSA nadir <0.2 ng/mL — not just ≥90% PSA decline — when assessing treatment response in mCSPC, as only the absolute threshold predicts improved survival and delayed progression. Adding an ARPI to ADT more than doubles the odds of reaching this target and should be considered the standard approach.
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