Importance of adding ADT to brachy boost therapy for men with unfavorable-risk prostate cancer

Last month, we looked at Level 1 evidence (highest level, superseding all previous studies) that for unfavorable-risk patients, brachy boost therapy (BBT) — i.e., external beam therapy (EBRT) with a brachytherapy boost to the prostate — has better results when accompanied by 18 months of androgen deprivation therapy (ADT) (see this link).

Now a meta-analysis by Jackson et al. has reaffirmed that finding. The two studies were probably submitted for publication at about the same time, which explains why the meta-analysis doesn’t include data from RTOG 01.03 RADAR. In the Jackson et al. meta-analysis (and the Medpage Today commentary), there were:

  • 6 randomized trials of EBRT with or without ADT, comprising 4,663 patients
  • 3 randomized trials of EBRT with or without a BBT, comprising 718 patients
  • One of those trials included ADT, the other two did not

Jackson et al. found that 10-year overall survival was:

  • Improved by 30% by the addition of ADT to EBRT
  • Not improved by the addition of BBT to EBRT (at least when adjuvant ADT was not included)
  • The addition of ADT had a bigger impact than the addition of BBT
  • The trial that included both ADT and BBT had the best results

Because this meta-analysis included trials with men from different risk levels, it gives no direction about which therapy is best for favorable- vs unfavorable-risk men. DART 01/03 GICOR proved that adjuvant ADT only provides an added benefit to EBRT in high-risk men (vs intermediate-risk men). Furthermore, BBT did not benefit and did add toxicity to favorable-risk patients (see this link).

Some of the trials did not include radiation doses now considered curative. The Jackson et al. meta-analysis also did not look at ADT duration.

Editorial note: This commentary was written by Allen Edel for The “New” Prostate Cancer InfoLink.

3 Responses

  1. Many of us have read this report. I, for one, am somewhat frustrated by large population studies like this one, that do not provide much insight into WHY ADT helps with RT and why it doesn’t help all men, or, more precisely why these studies are not more ergotic. We are still far from precision medicine that can pinpoint which man should have which treatment, including yes/no/duration of ADT and which kind of ADT.

  2. Dear Ethan:

    In all truth we do not know exactly why the combination of radiation therapy with ADT seems to work more effectively than either one alone in the treatment of certain groups of men with more aggressive or advanced forms of prostate cancer. We just know that it does. And it appears that there is some form of synergistic effect — in at least some but certainly not all patients.

    With regard to your question about “why these studies are not more ergotic”, I am assuming that you meant the term “ergodic” rather than “ergotic”.

    I am no statistician, but one of the problems in addressing the ergodicity of these types of medical data may have to do with the near impossibility of collecting — in advance — all of the data necessary to assess the scope of the problem, especially without a very clear hypothesis as to the nature of why the two types of therapy may have a synergistic effect. You’d probably need to take this question up with one of the statisticians who look at the data from studies like this. Holly E. Hartman at the University of Michigan appears to be your best bet in the case of this particular study! She has her own web site and appears to welcome communication since it gives her e-mail address and a comment box. Try asking her. You have nothing to lose, and maybe you can help to teach us all something new!

  3. Dear Sitemaster:

    It is very good to read this now. Pleasing, in fact. This is more confirmation that my 2009 treatment with neoadjuvant ADT EBRT BBT (2) ADT was correct. I guess some would quibble with the 3 years ADT that I got, but IMHO the Uppsala doctors were right to play safe. I am not complaining, as I was set up for probable death from under-treatment, in Amsterdam.

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