RADAR Trial: Short- vs Intermediate-Term Androgen Suppression and Zoledronic Acid in Locally Advanced Prostate Cancer
As reported by Denham et al in The Lancet Oncology, 10-year results of the phase III TROG 03.04 RADAR trial have shown that 18 months of androgen suppression plus radiotherapy is more effective than 6 months of androgen suppression plus radiotherapy in locally advanced prostate cancer, but no further benefit was observed with the addition of zoledronic acid to either regimen.
Study Details
In the open-label 2 x 2 factorial trial, 1,071 patients from 23 sites were randomly assigned 1:1:1:1 between October 2003 and August 2007 to 4 treatment groups:
- 6 months of neoadjuvant androgen suppression with leuprorelin and radiotherapy (short-term androgen suppression [STAS]; n = 268)
- 6 months of neoadjuvant and 12 months of adjuvant androgen suppression with leuprorelin and RT (intermediate-term androgen suppression [ITAS]; n = 268)
- STAS plus 18 months of zoledronic acid (n = 268)
- ITAS plus 18 months of zoledronic acid (n = 267).
All patients received radiotherapy to the prostate and seminal vesicles, starting from the end of the 5th month of androgen suppression.
The primary endpoint was prostate cancer–specific mortality analyzed in the intention-to-treat population.
Prostate Cancer–Specific Survival
Median follow-up was 10.4 years. At 10-year follow-up, no treatment interactions were observed between androgen suppression and zoledronic acid; the treatment groups were thus combined on the basis of duration of androgen suppression, with 536 patients in the STAS group and 535 in the ITAS group.
A total of 375 patients died, including 200 receiving STAS and 175 receiving ITAS; of these, 143 deaths (38%) were attributable to prostate cancer, including 81 among patients receiving STAS and 62 among those receiving ITAS. The adjusted cumulative incidence of prostate cancer–specific mortality was 13.3% in the STAS group vs 9.7% in the ITAS group (absolute difference = 3.7%, subhazard ratio [sHR] = 0.70, P = .035).
The addition of zoledronic acid did not affect prostate cancer–specific mortality. The adjusted cumulative incidence of prostate cancer–specific mortality was 11.2% among patients receiving zoledronic acid vs 11.7% among those not receiving zoledronic acid (absolute difference = −0.5%, sHR = 0.95, P = .78).
As noted by the investigators, another trial—the French Canadian Prostate Cancer Study IV trial, recently reported by Nabid et al in European Urology—found that 18 months of androgen suppression and radiotherapy was associated with a marked reduction in adverse patient-reported outcomes compared with 36 months of androgen suppression.
The investigators concluded, “Eighteen months of androgen suppression plus radiotherapy is a more effective treatment option for locally advanced prostate cancer than 6 months of androgen suppression plus radiotherapy, but the addition of zoledronic acid to this treatment regimen is not beneficial. Evidence from the [RADAR] and French Canadian Prostate Cancer Study IV trials suggests that 18 months of androgen suppression with moderate radiation dose escalation is an effective but more tolerable option than longer durations of androgen suppression for men with locally advanced prostate cancer, including intermediate- and high-risk elements.”
James W. Denham, MD, FRANZCR, of the School of Medicine and Public Health, University of Newcastle, is the corresponding author for The Lancet Oncology article.
Disclosure: The study was funded by the National Health and Medical Research Council of Australia, Novartis Pharmaceuticals Australia, AbbVie Pharmaceuticals Australia, New Zealand Health Research Council, New Zealand Cancer Society, and others. The study authors’ full disclosures can be found at thelancet.com.
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