In metastatic HSPC, therapy involves androgen deprivation therapy (ADT) with the addition of docetaxel or abiraterone in high volume/burden disease. In low volume/burden metastatic disease, abiraterone and local radiotherapy to the prostate is the current standard of care. In the very near future, there will be an update of data from the STAMPEDE trial regarding treatment of high volume and low volume metastatic disease for the docetaxel arm.
Recently, there have been many trials published assessing the role of new and familiar drugs in the metastatic HSPC disease. These are shown in table 1.
Table 1- Trials assessing the role of various drugs in the setting of metastatic HSPC:
In the non-metastatic CRPC disease, enzalutamide, apalutamide, and darolutamide have been assessed as well, as seen in table 2.
Table 2 – Trials assessing the role of various drugs in the setting of metastatic CRPC:
Like other cancers, the concept of “Precision medicine” will be incorporated for prostate cancer in the near future as well. Specifically, for patients with mismatch repair deficiency microsatellite instability (high) disease – pembrolizumab has been FDA approved with a 5% response rate. In DNA repair defects in homologous recombination genes like BRCA 1 and 2 – PARP inhibitors and platins have been used with promising results.
Many of the expectations from 2018 have been fulfilled. These include evidence that radiotherapy as local treatment is beneficial for low-burden metastatic disease, that administering androgen receptor antagonists earlier is beneficial (in metastatic HSPC, and non-metastatic CRPC), and that there are several ongoing biomarker trials assessing their roles in treatment decisions.
Dr. Silke concluded her talk with some of her expectations for 2019-2020:
1. In metastatic HSPC – androgen receptor antagonists will be a new option in addition to ADT. Additionally, the treatment combination of docetaxel and androgen receptor antagonists +/ - local treatment of the primary prostate cancer – will be beneficial.
2. In non-metastatic CRPC – treatment with androgen receptor antagonists will become the standard of care for the majority of patients with a short PSA, doubling time.
3. In metastatic CRPC – Precision medicine will become a reality, with pembrolizumab for MSI high/ dMMR; and PARP inhibitors for (some) of the DNA repair defects.
Finally, the issue of cost and availability will become more relevant, problematic and will be debated extensively.
Presented by: Silke Gillessen, MD, Professor and Chair in Genitourinary Oncology Systemic Therapy Research at The University of Manchester and The Christie NHS Foundation Trust, Co-founder of the Advanced Prostate Cancer Consensus Conference (APCCC)
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre @GoldbergHanan at the 34th European Association of Urology (EAU 2019) #EAU19 conference in Barcelona, Spain, March 15-19, 2019.