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How low do you need to go? Association between various prostate‐specific antigen response measures and clinical outcomes in metastatic castration‐sensitive prostate cancer in the Veterans Health Administration data
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How low do you need to go? Association between various prostate‐specific antigen response measures and clinical outcomes in metastatic castration‐sensitive prostate cancer in the Veterans Health Administration data

Cancer·August 10Open Access
OncologyPractice changingMetastatic Castration-Sensitive Prostate CancerRetrospective Cohort StudyAndrogen Deprivation TherapyAndrogen Receptor Pathway InhibitorOlder AdultErleadaNubeqaXtandiZytigaAbirateroneApalutamideDarolutamideDocetaxelEnzalutamide

Summary

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What was studied

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.

Key findings

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).

Study limitations

- 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.

Clinical implications

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.

Caveats

  • Generalizability is limited: the VHA population is predominantly older, male, and includes a high proportion of Black patients (29%), which may not reflect the broader mCSPC population.
  • Impact flag 'practice_changing' applied because PSA <0.2 ng/mL as the target metric directly contradicts the majority of current real-world physician practice (85% use % decline), though this is a retrospective observational study and causality cannot be established.
  • Plain language summary states data from 2018–2023 for index dates, while the methods section states VHA data from 2006–2024 — the broader date range reflects data availability, with index dates restricted to 2018–2023.
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  • Study sponsored by Pfizer and Astellas (codevelopers of enzalutamide); several authors are employees or shareholders of these companies — potential for sponsorship bias.

Related Questions

Explore related topics

What PSA nadir threshold best predicts survival in metastatic castration-sensitive prostate cancer?Does adding an ARPI to ADT improve PSA response rates in mCSPC compared to ADT alone?How should clinicians use PSA response to guide treatment de-intensification or escalation in mCSPC?

Publication Details

Year
2026
Journal
Cancer
Sample Size
n=4,890
Source
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