Results of the RADAR trial at 7.4 years of follow-up

The RADAR trial (also known as TROG 03.04) was a randomized trial of 6 months of androgen deprivation therapy (ADT) + radiation therapy versus 18 months of ADT + radiotherapy, with or without additional zoledronic acid therapy, in men with intermediate- and high-risk, locally advanced prostate cancer.

The basic results of this, rather complex, “2 × 2 factorial,” randomized trial were twofold:

  • After a median of 7.4 years of follow-up, there were no statistically significant differences in either all-cause (overall) mortality or prostate cancer-specific mortality among the four groups of patients.
  • There may be some benefit associated with 18 months of ADT (as opposed to 6 months of ADT) and with the addition of zoledronic acid in patients with a Gleason score of 7 or higher at time of diagnosis, but this second result is based on a post-hoc analysis and has to be interpreted with great caution.

To get into the details, as reported by Denham et al. in The Lancet Oncology, the RADAR trial enrolled patients in Australia and New Zealand between October 20, 2003, and August 15, 2007. All patients had either T2aN0M0 disease with a PSA level of ≥10 ng/ml and a Gleason score of ≥ 7 or T2b-4N0M0 disease (regardless of PSA and Gleason score). The total number of patients enrolled was 1,071 and they were randomly assigned to one of four groups, as follows:

  • Patients in Group A (n = 268) were treated with leuprolide acetate for 6 months of neoadjuvant ADT and then radiation therapy.
  • Patients in Group B (n = 268) were treated with leuprolide acetate for 6 months of ADT and then radiation therapy and zoledronic acid.
  • Patients in Group C (n = 268) were treated with leuprolide acetate for 6 months, then had radiation therapy and another 12 months of leuprolide acetate.
  • Patients in Group D (n = 267) were treated with leuprolide acetate for 6 months, then had radiation therapy and another 12 months of leuprolide acetate and zoledronic acid.

The outcomes data at an average (median) of 7.4 years of follow up showed that:

  • The incidence rates of prostate cancer-specific mortality were
    • 4.1 percent in Group A
    • 7.8 percent in Group B
    • 7.4 percent in Group C
    • 4.3 percent in Group D
  • The incidence rates of overall or all-cause mortality were
    • 17.0 percent in Group A
    • 18.9 percent in  Group B
    • 19.4 percent in Group C
    • 13.9 percent in Group D
  • The incidence rates of biochemical (PSA-based) progression were
    • 34.2 percent in Group A
    • 39.6 percent in Group B
    • 29.2 percent in Group C
    • 26.0 percent in Group D (20·8—31·4) in the ITAS plus zoledronic acid group.
    • Compared to patients in Group A, patients in Group D had a statistically significant reduction in risk for biochemical progression.
  • The incidence rates of local clinical progression were
    • 4.1 percent in Group A
    • 6.1 percent in Group B
    • 1.5 percent in Group C
    • 3.4 percent in Group D
  • The incidence rates of progression to bone were
    • 7.5 percent in Group A
    • 14.6 percent in Group B
    • 8.4 percent in Group C
    • 7.6 percent in Group D (4·8—11·2), respectively.
    • Compared to patients in Group A, patients in Group B had a statistically significant increase in risk for bone progression.
  • Incidence rates of any distant progression were
    • 14.7 percent in Group A
    • 17·3 percent in Group B
    • 14.2 percent in Group C
    • 11.1 percent in Group D
  • Incidence rates for secondary therapeutic intervention were
    • 25.6 percent in Group A
    • 28.9 percent in Group B
    • 20.7 percent in Group C
    • 15.3 percent in Group D
  • Reductions in PSA progression and decreased need for secondary therapeutic intervention among patients in Group D were restricted to tumors with a Gleason score of 8—10
  • Patients in Group C and D did better than patients in Group A and B when they had tumors with Gleason scores of 7 or lower.
  • Long-term morbidity and quality-of-life scores were not affected adversely by 18 months of ADT or by treatment with zoledronic acid.

As we have noted previously, the post-hoc data suggesting differing outcomes based on Gleason score (given in italic type above) need to be interpreted with great caution because they were not pre-specified in the trial protocol.

6 Responses

  1. I just did a post at another site a few days ago where I put their findings in a table format that may be easier to read.

    There are several randomized clinical trials now concerning Zometa that all seem to have contradictory findings. I am at a loss to reconcile them with one another and hope that your readers may provide insight.

  2. I’m not entirely sure what to make of this. I’m pT3b and Gleason 9 (very high risk), have had a radical prostatectomyand salvage radiation therapy, and am scheduled for a second 3-month shot of Lupron shot. So will I need 6 or 18 months of Lupron, and what is zoledronic acid?

  3. Was there any reason why Group B fared so badly in progression to bone incidence rates?

  4. Dear Allen:

    I think it is extraordinarily difficult to “reconcile” all the available data because so much depends on the precise descriptions and limitations on the men enrolled into the trials. As a consequence, you can’t necessarily even say with confidence that the discrepancies between the trial data are necessarily “contradictory.”

    I note that there has been considerable discussion of this topic on the PCAdvocates board sting that you mention — with no resolution in sight.

  5. Robert:

    Zoledonic acid or Zometa is an injectable drug that can be used to prevent loss of bone density and early onset of “skeletally related events” or SREs up to and including actual fractures in men who are receiving androgen deprivation therapy. However, …

    There is still no clarity about the “best” time to initiate treatment with zoledronic acid. For example, some experts would argue it is best reserved until a patiuent has metastatic disease and is on long-term ADT as opposed to short-term ADT.

    With respect to whether you are better served by 6 or 18 months of ADT, that’s a question you need to raise with your doctors because it depends on all of your risk indicators and not just your original clinical stage and Gleason score. For example, do you have any idea what your PSA doubling time was after surgery and before you had the salvage radiation?

  6. Paul:

    Sorry, I have no clue. You know what I know.

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