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On-treatment PSA linked to long-term survival in prostate cancer, post-hoc analysis finds

Researchers reported that PSA values, combined with metastatic volume or nodal status, improved estimation of 8-year survival, with prospective evaluation needed before any use in treatment personalization.

  • Mahaz Kayani, MBBS; Laura Murphy, PhD; Peter Dutey-Magni, PhD; Sarah Howlett, MBBS; Ashwin Sachdeva, PhD FRCS; Minal Padden-Modi, MBBS; et al.

  • May 1, 2026

  • The Lancet Oncology
  • The Lancet Oncology, Volume 27, Issue 5, Pages 625–636
  • 10.1016/S1470-2045(26)00066-5

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Evidence before this study

We searched PubMed for clinical trials published in English between database inception and Oct 2, 2025, using the terms “prostate cancer”, “prostate-specific antigen”, “hormone-sensitive” or “castration-sensitive”, “response”, and “clinical trial”. We identified 12 post-hoc analyses from phase 3 randomised controlled trials and one meta-analysis in patients with metastatic disease, and two post-hoc analyses plus one meta-analysis in patients with non-metastatic disease. These studies consistently showed that a lower on-treatment prostate-specific antigen (PSA) concentration is associated with improved overall survival, with the most common threshold investigated being a concentration of 0·2 ng/mL or less. However, most analyses assessed PSA at 6–7 months after treatment initiation, and the optimal timing of PSA measurement and threshold of PSA concentration have not been validated prospectively. No study has evaluated the prognostic role of PSA concentration in patients receiving androgen receptor pathway inhibitors for high-risk non-metastatic disease. Similarly, it is unclear whether combining PSA response with other clinical markers, such as CHAARTED metastatic volume or nodal status for patients with non-metastatic disease, could improve prognostic accuracy.

Added value of this study

This is the largest analysis of PSA nadir within a randomised controlled trial framework. We showed that PSA measured as early as 6 weeks or 12 weeks is associated with long-term survival, alongside the established 24-week timepoint. To our knowledge, we show for the first time the prognostic value of PSA in patients with very high-risk non-metastatic disease treated with an androgen receptor pathway inhibitor. On-treatment PSA values combined with metastatic volume or nodal status improve estimation of 8-year survival estimates.

Implications of all the available evidence

On-treatment serum PSA is a robust prognostic marker, with improved survival prediction when combined with conventional imaging-derived features. Future clinical trials should evaluate use of on-treatment PSA concentration combined with metastatic burden to personalise treatment intensification or de-intensification.

Source: The Lancet Oncology

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