Sunday, September 11, 2022

Short-term androgen annihilation in non-metastatic recurrent men after SRT delays progression

 A difficult question for patients who still having rising PSA after prostatectomy and salvage radiation is: Is there any advantage to starting advanced hormone therapy before metastases are visible?

Rahul Aggarwal presented the early results of the PRESTO trial. Patients (n=504) were chosen who had the following characteristics:

  • Failed prostatectomy and salvage radiation (85%). Half of those who had salvage radiation, had adjuvant ADT at the time
  • PSA>0.5 ng/ml
  • PSA doubling time (PSADT) ≤ 9 month
  • no metastases on conventional imaging (bone scan/CT/MRI)

Patients were randomly assigned to one year of any of the following treatments:

  1. ADT only
  2. ADT+apalutamide
  3. ADT+abiraterone+apalutamide

With follow-up of 21 months, biochemical progression-free survival (bPFS, PSA stayed under 0.2 ng/ml) was:

  • 20 mos. in Group A
  • 25 mos. in Group B (48% improvement vs Group A)
  • 26 mos. in Group C  (52% improvement vs Group A)
  • No significant differences attributable to PSADT
  • Group C wasn't significantly different from Group B (Zytiga added little)

Other findings:

  • Testosterone recovered in 4-5 months in all groups
  • More hypertension with abiraterone

Other trials have looked at adding a limited term of 2nd line hormonal medicines when there is rapid PSADT but before metastases have been discovered on conventional imaging.

  • Spetsieris et al. added abiraterone for 8 months. Afterwards, bPFS was 27 mos vs 20 mos. for ADT-only.
  • Madan et al. reported substantial PSA control with intermittent use (two 3-month cycles) of enzalutamide alone without ADT. PSA didn't rise for 6-7 months after the first and second cycles.
  • Neal Shore reported a similar benefit to apalutamide in the EMBARK trial.

With detection of metastases with PSMA PET scans, the advantage of early intervention will become clearer. There is also a clearer advantage for men with a higher Decipher score.  Recurrent men with rapid PSADT after salvage radiation should consider a short-term intervention with one of the advanced hormonals.


  1. Thank you. Is there any analysis of the use of external estrogen for the management of PSA following RP and SRT? I have not seen the completion of the English trial.

    1. Short-term effects of transdermal estradiol in men undergoing androgen deprivation therapy for prostate cancer: a randomized placebo-controlled trial
      Nicholas Russell, Rudolf Hoermann, Ada S Cheung, Michael Ching, Jeffrey D Zajac, David J Handelsman, Mathis Grossmann
      2018 European Journal of Endocrinology
      This study used two low doses of daily transdermal E2 gel to assess the effects on circulating E2 concentrations in men with prostate cancer with suppressed endogenous E2 production arising from androgen ... Nicholas Russell, Rudolf Hoermann, and Jeffrey D Zajac declare that they have no conflict of interest. ... hepatic estrogen exposure. ...
      doi:10.1530/eje-17-1072 pmid:29549104 fatcat:wkjlcftvwvcwrkhlqmjs7x6r5u