It is currently known that androgen deprivation therapy (ADT) remains a fixed part of therapy, and that radiotherapy improves survival of patients with low volume metastatic disease, implying benefit in patients with node-positive non-metastatic disease.
The beneficial treatment combinations in M0 HSPC include ADT plus either radiotherapy, docetaxel or abiraterone. The combination of radiotherapy plus ADT and either docetaxel or abiraterone have limited evidence to date, and the combination of ADT + docetaxel+ androgen receptor (AR) targeting agent +radiotherapy has no known evidence.
Both the HORRAD trial and the STAMPEDE -radiotherapy trial showed a benefit of radiotherapy aimed at the primary tumor with low-volume metastatic disease.1,2 Radiotherapy was shown to improve survival from 73% to 81% at 3 years in selected patients with low-volume metastatic disease (HR 0.68, 95% CI 0.52-0.90, p=0.007, p=0.0098), while it did not improve survival for unselected patients. According to Dr. James, this means that there is benefit implied to the N+M0 disease stage.
Next, Dr. James discussed the role of docetaxel in M0 and M1 HSPC. In a meta-analysis by Vale Cl et al.3 including 2993 men, there was a 15% reduction in failure events (from 80% to 65%) at 4 years after docetaxel treatment in M1 HSPC patients. Moreover, there was a 10% absolute increase in overall survival (from 40% to 50%)3 In M0 HSPC men, there was an 8% absolute reduction in failure events (from 70% to 62%) at 4 years, and there was a 5% potential improvement in overall survival (from 80% to 85%) at 4 years. Dr. James concluded that docetaxel has a consistent effect on failure-free survival (FFS) and that the individual trials are underpowered with respect to overall survival. There is evidence that there is an interaction between radiotherapy and docetaxel, with data suggesting that the only benefit seen is in patients not getting radiotherapy. Further data regarding this will be presented in the ESMO 2019 meeting.
Next, abiraterone’s role was discussed in high-risk M0 HSPC. There is evidence suggesting that both FFS and metastases free survival (MFS) are improved after the addition of abiraterone to ADT when compared to ADT alone for 2 years. There is also strong evidence for synergy between abiraterone and radiotherapy.
The choice of whether to give docetaxel and AR therapy is not simple. Evidence to give both together is still pending. In a study comparing 566 patients to either ADT + docetaxel or ADT +abiraterone4 abiraterone was strongly shown to be better in FFS and progression-free survival, while weakly shown to be better in MFS. No difference was seen between abiraterone and docetaxel in cause-specific survival and overall survival.
Dr. James concluded his talk stating that ADT plus one drug therapy (docetaxel or abiraterone) improves FFS and increases the quality of life in M0 HSPC. ADT + radiotherapy improves survival in low volume mHSPC and M0 HSPC. Available data suggest a synergistic effect with abiraterone and radiotherapy. Lastly, there is evidence supporting ADT + radiotherapy + 2 years of abiraterone in node-positive prostate cancer patients.
Presented by: Nicholas James, BSc, MB, BS, FRCP, FRCR, PhD, Institute of Cancer and Genomic Sciences, NIHR Senior Investigator, Professor of Clinical Oncology, University of Birmingham, United Kingdom
Written by: Hanan Goldberg, MD, Urology Department, SUNY Upstate Medical University, at the 2019 Advanced Prostate Cancer Consensus Conference (APCCC) #APCCC19, Aug 29 - 31, 2019 in Basel, Switzerland
References:
- Boeve LMS et al. Effect on Survival of Androgen Deprivation Therapy Alone Compared to Androgen Deprivation Therapy Combined with Concurrent Radiation Therapy to the Prostate in Patients with Primary Bone Metastatic Prostate Cancer in a Prospective Randomised Clinical Trial: Data from the HORRAD Trial. European Urology. 2019 Mar;75(3):410-418.
- Parker CC et al. Radiotherapy to the primary tumour for newly diagnosed, metastatic prostate cancer (STAMPEDE): a randomised controlled phase 3 trial. Lancet Oncology. 2018 DOI:https://doi.org/10.1016/S0140-6736(18)32486-3.
- Vale CL et al. Addition of docetaxel or bisphosphonates to standard of care in men with localised or metastatic, hormone-sensitive prostate cancer: a systematic review and meta-analyses of aggregate data. Lancet Oncology. 2016.DOI:https://doi.org/10.1016/S1470-2045(15)00489-1.
- Sydes MR et al. Adding abiraterone or docetaxel to long-term hormone therapy for prostate cancer: directly randomised data from the STAMPEDE multi-arm, multi-stage platform protocol. Annals of Oncology. 2018 1;29(5):1235-1248. doi: 10.1093/annonc/mdy072.