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Impact of PSA nadir, PSA response and time to PSA nadir on overall survival in real-world setting of metastatic

Mike Wenzel1, Benedikt Hoeh1, Fabienne Hurst1

  • 1Department of Urology, University Hospital Frankfurt, Goethe University Frankfurt am Main, Frankfurt, Germany.

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Summary

Achieving a prostate-specific antigen (PSA) nadir below 0.02 ng/mL and a PSA response of 99% or higher are linked to improved overall survival (OS) in metastatic hormone-sensitive prostate cancer (mHSPC) patients treated with combination therapies.

Keywords:
mCSPCmHSPCmetastatic prostate cancermortalitysurvival

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Area of Science:

  • Oncology
  • Urology

Background:

  • Prostate-specific antigen (PSA) nadir, response, and time to nadir (TTN) are critical in metastatic hormone-sensitive prostate cancer (mHSPC).
  • Evaluating these markers in the context of modern combination therapies is essential for refining prognostic models.

Purpose of the Study:

  • To assess the prognostic impact of PSA nadir, PSA response, and TTN on overall survival (OS) in mHSPC patients receiving combination therapies.
  • To identify optimal PSA nadir thresholds and evaluate the significance of deep PSA response and prolonged TTN.

Main Methods:

  • Retrospective analysis of 238 mHSPC patients treated with combination therapies.
  • Evaluation of various PSA nadir cut-offs (including ultra-low levels), PSA response (≥99%), and TTN categories (<3, 3-6, 6-12, >12 months).
  • Multivariable Cox regression models and sensitivity analyses in de novo and high-volume mHSPC subgroups.

Main Results:

  • Significantly better OS was observed with PSA nadir cut-offs of <0.2 ng/mL (median OS 96 months) and <0.02 ng/mL (not reached) compared to higher levels.
  • A PSA response of ≥99% was strongly associated with improved OS (p<0.02), as was a longer TTN (e.g., >12 months associated with 96 months median OS).
  • These findings were consistent across de novo and high-volume mHSPC subgroups and after multivariable adjustment.

Conclusions:

  • In the current era of combination therapies for mHSPC, achieving a PSA nadir <0.2 ng/mL or <0.02 ng/mL predicts superior overall survival.
  • A relative PSA response of ≥99% and a longer time to PSA nadir are clinically important indicators of favorable long-term outcomes.