ASCO GU 2018: Ten-year final results of the TROG 03.04 (RADAR) randomized phase-III trial

San Francisco, CA ( Historical data from RTOG 92.02 and EORTC 22961 have shown that long-term androgen deprivation therapy (ADT) is more effective than short-term ADT in men undergoing radiotherapy for clinically localized intermediate or high risk prostate cancer. However, long-term ADT carries with it a range of side-effects including sexual dysfunction, weight gain, bone density loss, cognitive dysfunction, and sarcopenia, to name a few.

During the prostate cancer session at the GU-ASCO 2018 meeting, Dr. David Joseph, a radiation oncologist from Sir Charles Gairdner Hospital in Perth, West Australia, presented data from the TROG 03.04 (RADAR) trial, which evaluated the effect of intermediate duration (18 months) adjuvant ADT plus zoledronic acid in men undergoing radiotherapy for clinically-localized, intermediate or high risk prostate cancer.

In this phase-III randomized, controlled trial, men were randomized to either 6 months of ADT plus radiotherapy versus 18 months of ADT plus radiotherapy, with or without the addition of zoledronic acid, a bisphosphonate which improves bone density, and which may also have anti-tumor activity in bone. Inclusion criteria included clinical T2-T4 N0M0 disease. 1071 men were enrolled from 2003-2007. The median follow-up was 10.4 years. The primary endpoint of the study was prostate-cancer specific mortality. Secondary endpoints included PSA progression, time to castration-resistance, secondary therapeutic interventions, all-cause mortality, quality of life, and adverse treatment effects.

At 10 years of follow-up Dr. Joseph and his colleagues found that 18 months of ADT conferred a 30% reduction in prostate cancer-specific mortality as compared to 6 months of ADT. There was a 29% decrease in distant progression of disease in the 18 month group, as well as a 35% decrease in PSA progression. The need for secondary therapeutic intervention was decreased by 34% in the 18 month group. Additionally they found that the time to development of castrate-resistant disease was decreased in the 18 month ADT group (HR 0.63, p = 0.004). They found no change in soft tissue progression or all-cause mortality between the two groups. Quality of life was similar between the two groups. Finally, they did not find any clinically significant improvements in the studied outcomes with the addition of zoledronic acid to ADT.

The study reached the conclusion that 18 months of ADT is more effective than 6 months of ADT in men undergoing radiotherapy for clinically localized prostate cancer, and that the addition of zoledronic acid to ADT provides no significant clinical benefit. Additional information will be learned in the future from the RADAR trial, including including optimal radiation dosing and the cost-effectiveness of 18 months of ADT.

Presented by: Dr. David J. Joseph, Sir Charles Gairdner Hospital, Perth, Western Australia

Written by: Brian Kadow, MD, Fox Chase Cancer Center, Philadelphia, PA at the 2018 American Society of Clinical Oncology Genitourinary (ASCO GU) Cancers Symposium, February 8-10 - San Francisco, CA