medwireNews: Patients treated with 18 months of androgen suppression plus radiotherapy have a significantly lower rate of prostate cancer-specific death at 10 years than those who receive 6 months of androgen suppression and radiotherapy, researchers report.
The long-term outcomes from the phase III TROG 03.04 RADAR trial show that the 10-year cumulative incidence of prostate cancer-specific mortality was 9.7% for the 535 men with intermediate- and high-risk prostate cancer randomly assigned to receive intermediate-term androgen suppression (ITAS) with leuprorelin (22.5 mg every 3 months) for a total of 18 months (6 months neoadjuvant, 12 months adjuvant) alongside external-beam radiotherapy to the prostate and seminal vesicles with or without zoledronic acid.
This was significantly lower than the 13.3% rate observed among the 536 men randomly assigned to receive short-term neoadjuvant androgen suppression (STAS) with leuprorelin for 6 months plus radiotherapy with or without zoledronic acid, resulting in an absolute difference of 3.7% and a sub-hazard ratio of 0.70.
Writing in The Lancet Oncology, James Denham (University of Newcastle, New South Wales, Australia) and co-investigators say their findings indicate that “[l]ess morbid treatments using intermediate durations of androgen suppression such as 18 months, alongside better targeted, increased doses of prostatic radiotherapy, will result in better outcomes and will provide an effective and tolerable treatment option for men with locally advanced prostate cancer including high and intermediate risk elements.”
All of the study participants were aged 18 years or older with either clinical stage T2b-4, N0 M0 prostate tumors or with stage T2a, N0 M0 tumors and Gleason scores of 7 or higher and baseline prostate-specific antigen (PSA) concentrations of at least 10 μg/L.
There was no significant difference in all-cause mortality between the patients who received ITAS and those who received STAS (28.0 vs 32.3%), but those in the ITAS group had significantly lower rates of distant progression (20.7 vs 27.5%), bone progression (15.8 vs 23.3%), local progression (4.9 vs 7.9%), PSA progression (34.0 vs 45.9%), secondary therapeutic intervention (26.6 vs 36.8%), and transition to castration resistance (11.3 vs 17.1%) than those in the STAS group.
The researchers note that the addition of zoledronic acid had no significant effect on prostate cancer-specific mortality and did not prevent bone metastases or improve any of the other endpoints evaluated.
They also point out that, since the preliminary report of the trial data in 2014, one additional case of osteonecrosis of the mandible occurred in a patient who received ITAS plus zoledronic acid, bringing the total to three and giving an event rate of 0.57% among the 530 patients who received zoledronic acid and were evaluated for safety. The overall drug-related serious adverse event rate was 1% among the 1065 evaluable patients and there were no treatment-related deaths during the study.
Denham and co-authors conclude that although further data on preexisting comorbidities and the suitability of radiation dose escalation are needed to establish the optimal duration of androgen suppression for individual men, at present, “18 months of androgen suppression plus radiotherapy is an effective and welltolerated therapeutic option for men with locally advanced prostate cancer including high and intermediaterisk elements.”
By Laura Cowen
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