Rising PSA after prostatectomy is common; as many as 40% of patients may experience biochemical recurrence within 10 years. Additional evidence-based guidance is needed about whom to treat, which therapies to use, and how long to treat.
The PRESTO trial is collecting data to address this vital question. Results were presented at the European Society of Medical Oncology (ESMO) Congress 2022. Led by PCF-funded investigator Rahul Aggarwal, MD, of UCSF, the study enrolled 500 patients with “high-risk” biochemical recurrence after prostatectomy. This was defined as a PSA doubling time of 9 months or less, which is associated with a higher likelihood of developing metastases and of death from prostate cancer. Patients were randomized to one of three treatment arms:
- ADT (such as Lupron) alone (the “control”)
- ADT + apalutamide (a novel hormonal therapy)
- A “triplet” combination of ADT + apalutamide + abiraterone (a novel hormonal therapy that works in a different way than apalutamide).
Patients received treatment for one year and were then followed over time to assess outcomes of interest. The key outcome was PSA progression, defined as a rise in PSA of 0.2 ng/mL.
The initial results showed that both of the experimental arms were superior to the control (ADT only) arm. Adding apalutamide to ADT prolonged the time to PSA progression by 4.6 months vs ADT alone. The triplet combination treatment prolonged the time to PSA progression by 6 months. In terms of side effects, hypertension was more common in the combination treatment arms, and was highest in patients on the triplet therapy. The study is continuing to follow participants to collect data on development of metastases, quality of life, and development of resistance to hormone therapy.
What this could mean for patients: The PRESTO trial may help to fill in the current knowledge gap about how best to treat patients with rising PSA after surgery who do not yet have metastases visible on scans. It will provide information on key factors such as the optimal intensity of hormonal therapy (one, two, or three drugs), and the effects of a finite (one-year) duration of treatment.