Background
Phase III RCT (TROG 03.04 RADAR Trial — Randomized Androgen Deprivation and Radiotherapy). 1,071 patients with locally advanced prostate cancer (PSA 10–20 ng/mL or Gleason ≥7 or clinical stage T2b–T3), enrolled 2003–2007. Tested: (1) 6 months vs 18 months of ADT with EBRT, and (2) the addition of zoledronic acid. This report (Joseph IJROBP 2020) focuses on the 10-year outcomes of the ADT duration randomization.
Interventions and follow up
Arm A: RT (66–74 Gy/33–37 fx) + 6 months ADT (leuprolide)
Arm B: RT + 18 months ADT (leuprolide)(Zoledronic acid 4 mg q3 months × 4 doses factorially randomized in both arms)
Primary endpoint: Prostate cancer-specific mortality
mFollow up: Median ~10 year
Arm B: RT + 18 months ADT (leuprolide)(Zoledronic acid 4 mg q3 months × 4 doses factorially randomized in both arms)
Primary endpoint: Prostate cancer-specific mortality
mFollow up: Median ~10 year
Results
10-year prostate cancer-specific mortality: 10.3% (18-month ADT) vs 13.3% (6-month ADT), HR 0.73 (95% CI 0.49–1.10), P=.14 (not significant in all patients)
Subgroup: Gleason 8–10: Significant benefit with 18 months ADT (HR ~0.54, P=.03)
OS: Numerically improved with 18-month ADT but not significant overall
Distant metastases: Improved with 18-month ADT in high-risk subgroup
Subgroup: Gleason 8–10: Significant benefit with 18 months ADT (HR ~0.54, P=.03)
OS: Numerically improved with 18-month ADT but not significant overall
Distant metastases: Improved with 18-month ADT in high-risk subgroup
Adverse events
Main adverse events: Longer ADT (18 months): significantly more erectile dysfunction, hot flashes, fatigue, and osteoporosis-related fractures vs 6 months. Zoledronic acid improved bone mineral density but did not improve cancer outcomes.
Conclusions
Extended ADT (18 months vs 6 months) did not significantly improve prostate cancer-specific mortality in the overall population at 10 years, but demonstrated significant benefit in the high-risk Gleason 8–10 subgroup. These results support prolonged ADT (18 months or more) specifically in high-risk patients, consistent with EORTC 22863 and RTOG 9202. Zoledronic acid did not improve cancer outcomes.
Key Limitations
Key Limitations: Not powered for prostate cancer-specific mortality as primary endpoint across all subgroups. The trial predates IMRT dose escalation (74 Gy, mixed 3D-CRT/IMRT). Gleason grading underwent update (ISUP 2014) during the trial. The ADT duration question is now better addressed by meta-analyses showing ~18 months for intermediate-high risk and ≥24 months for high-risk. Zoledronic acid finding (no benefit) was negative but is consistent with the STAMPEDE trial data for metastasis-prevention.
Clinical Context
The RADAR trial adds to the body of evidence on ADT duration for prostate cancer RT. The subgroup finding supporting 18 months ADT in Gleason 8–10 is consistent with current NCCN guidelines recommending 18–36 months ADT for high-risk prostate cancer treated with RT. The negative result for zoledronic acid (no oncologic benefit) is consistent with the STAMPEDE zoledronic acid arm (Saad 2013 NEJM). Modern protocols add 18–36 months ADT for high-risk disease, with newer agents (abiraterone, enzalutamide) being evaluated in the STAMPEDE and ATLAS trials.
References