Efficacy of continuous ADT and correlation to nadir serum T levels

We had “missed” a poster presented at the recent meeting of the European Urology Association that appears to “put to bed” — in a positive fashion — the question of a relationship between nadir serum testosterone (T) levels in men on continuous androgen deprivation therapy (ADT) and the long-term effectiveness of continuous ADT.

The actual poster by Klotz et al. can now be found on the UroToday web site, along with commentary by Dr. Klotz and a separate write up by a rapporteur for UroToday. (You do have to join UroToday to be able to see this material, but membership is free for patients and advocates.)

Klotz and his colleagues re-analyzed selected data from a study (the NCIC/SWOG/UKCCR PR7 study, reported out in early 2011) in which they had shown that, for men who had biochemical progression after definitive treatment for localized prostate cancer, intermittent ADT was non-inferior to continuous ADT.

What Klotz and his colleagues have done now is to look at the data from the 696 patients in that study who were randomized to receive continuous ADT to see whether their nadir serum T level while on ADT was correlated to patient survival and/or other factors.

Here are the core study findings:

  • 626/696 men on continuous ADT in the PR7 study had at least three serum T levels measured during their first year on ADT.
  • Median overall follow-up was 8 years.
  • Among those 626 patients
    • 226 went on to develop castration-resistant prostate cancer (CRPC).
    • Median time to development of CRPC was 10.0 years

These 626 patients could be categorized into three groups as follows:

  • Group A included 489 patients with a nadir serum T level of < 0.7 nmol/l (i.e., < 20 mg/dl).
  • Group B included 129 patients with a nadir serum T level between 0.7 and 1.7 nmol/l (i.e., between 20 and 50 mg/dl).
  • Group C included 8 patients with a nadir serum T level of > 1.7 nmol/l (i.e., > 50 mg/dl)

After categorizing the patients in this way, Klotz et al. were able to show conclusively that

  • Men in Group A exhibited a significant improvement in cancer-specific survival by comparison to men in either Group B or Group C.
  • Men in Group A exhibited a significant improvement in duration of response to continuous ADT by comparison to men in either Group B or Group C.
  • Men in Group C exhibited a significant decrease in overall survival after becoming castration-resistant by comparison to men in Group A or Group B.

The athors note in the poster that, based on these data, serum testosterone levels should be regularly assayed in men on continuous ADT, and the form of ADT being used should be modified, as and when necessary, to ensure that serum T levels are maintained below 0.7 nmol/l (i.e., lower than 20 mg/dl) for as long as this can be accomplished.

This of course raises the question (which is not a new one) as to whether it should also be standard practice to measure serum dihydrotestosterone (DHT) levels, since we know that DHT is the biochemical derived from testosterone that acts on prostate cancer cells to drive cancer cell growth. A subset of specialists has argued in favor of this for some time. As yet, we still don’t have data from a really large study that is capable of testing this very reasonable hypothesis. And then there is the question of whether, if there is a direct correlation to serum DHT levels, whether there is any need to measure serum T levels.

The other question raised by this study is, “Was there a comparable effect of any type in the intermittent ADT arm of the PR7 study?” In other words, was there a analogous correlation between nadir serum T levels and response to intermittent ADT? This might or might not be the case, and one wonders whether Klotz and his colleagues have already looked at this question — and if not, why not.

One Response

  1. Might also be interesting to look at PSA nadir and how long it took to arrive at that level. One could postulate that the higher the PSA nadir, the quicker the time to mCRPC.

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