EAU 2018: Hormone-Naive Prostate Cancer

Copenhagen, Denmark (UroToday.com)  Dr. Joniau gave an overview of hormone-naïve prostate cancer (HNPC). Approximately 5% of the screened population present with de novo metastatic prostate cancer. This represents 1/3 of the prostate cancer (PC) death in the USA each year. The remaining 2/3 of patients relapse after prior localized therapy. They undergo rapid progression to metastasis, with transformation of HSPC to castrate resistant prostate cancer (CRPC), and then to death.  The median time from radical prostatectomy to PSA failure is 24 months (12-44). The median time from PSA failure to metastasis is 32 months (2-129), and finally the median time from metastasis to PC specific mortality is 82 months (7-181). Overall, from PC relapse to PC specific death the median time is 132 months (12-204).

Androgen deprivation therapy (ADT) is the back-bone of HSPC therapy, and the volume of metastatic disease is prognostic. The addition of docetaxel to ADT prolongs overall survival (OS), especially in high volume disease (STAMPEDE and CHAARTED studies). The addition of abiraterone to ADT prolongs OS as well (LATITUDE and STAMPEDE). LATITUDE demonstrated 38% risk reduction of death and 53% risk reduction of progression/death. When comparing ADT + abiraterone to ADT+docetaxel [1] there was strong evidence for favoring abiraterone when looking at failure free survival and progression free survival. No good evidence of a difference was observed in cause specific survival and overall survival. Abiraterone has been demonstrated to be superior to docetaxel in efficacy, acute toxicity, toxic deaths, and convenience. However, the costs of abiraterone are significantly higher than that of docetaxel. There is an ongoing trial attempting to assess if the combination of ADT + abiraterone + docetaxel (PEACE – 1) is even better than each of them alone.

When deciding whether to give docetaxel or abiraterone, we need to understand if the patient is fit to receive docetaxel. Next, we need to know if the patient has a high enough burden of disease to potentially benefit from early docetaxel. Known risk factors in HSPC is high volume disease and de novo metastatic disease. These known risk factors should also be incorporated when choosing between docetaxel and abiraterone. Lastly, cost is a significant factor in choosing between these two treatments, as abiraterone is significantly more expensive than docetaxel. Several factors can help us choose docetaxel over abiraterone, aside from lowered cost. These include the fact that despite more short term adverse events with docetaxel, it is done in 18 weeks. Furthermore, abiraterone requires more clinic visits and long-term monitoring. Additionally, abiraterone can be added on later more easily than docetaxel, which we will not be able to administer to the patient is too frail. Our aim should be to get as many therapies as possible.

The STOMP trial compares between surveillance and metastasis directed therapy for oligometastatic prostate cancer recurrence. Preliminary results demonstrate that 75% of patients on MDT compared to 35% of surveillance patients undergo PSA decline [2] Additionally, this study shows an increased biochemical recurrence free survival, and ADT free therapy in the local treatment arm. This phase 2 study represents the first positive evidence of local therapy for oligometastatic disease. 

Dr. Joniau concluded his talk by stating that in de novo metastatic disease:

  1. Addition of docetaxel or abiraterone to ADT are efficient
  2. Treatment selection should consider all patient factors, tumor factors and careful counseling
  3. The ultimate goal should be not to miss the opportunity to receive all treatments
In the setting of oligometastatic disease, the first randomized controlled trial shows that there is benefit in local treatment in oligometastatic disease, manifesting in an 8 month delay of starting ADT.


Presented by: S. Joniau

References:
[1] Sydes et al ESMO 2017
[2] Ost et al. JCO 2018

Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, twitter: @GoldbergHanan at the 2018 European Association of Urology Meeting EAU18, 16-20 March, 2018 Copenhagen, Denmark
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