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.