Serum T and extended survival on ADT “upgrading”

Could serum testosterone levels predict the effectiveness of combined androgen deprivation (ADT2) — through addition of an antiandrogen — in men with progressive prostate cancer and a rising PSA on LHRH agonist therapy alone?

Hashimoto et al. looked at data from 30 of their Japanese patients who had a rising PSA after LHRH agonist therapy and who were then “upgraded” to ADT2 by the addition of either bicalutamide 80 mg daily (n = 21) or flutamide 375 mg daily (n = 9).

They classified their patients into one of two groups based on their serum testosterone levels immediately prior to the addition of the antiandrogen:

  • 22 patients had a serum testosterone level of ≥ 5 ng/dl (Group A).
  • 8 patients had a serum testosterone < 5 ng/dl (Group B).

The researchers wanted to know if the serum testosterone level prior to initiation of additional antiandrogen therapy had any effect on patient response to treatment, which they defined as a decrease in the patients’ PSA by ≥ 50 percent from the PSA levels immediately before addition of the antiandrogen.

The results of their analysis showed the following:

  • The average (median) follow-up period was 52.5 months.
  • The initial response rate was about twice as high in Group A (77.3 percent) than in Group B (37.5 percent).
  • 24/30 patients (80.0 percent) demonstrated PSA progression during the follow-up period (which means that 6/30 patients showed no progression within the median follow-up of 4.4 years).
  • At 1 year from initiation of ADT2, the rate of biochemical progression was just 31.8 percent in Group A but 100 percent in Group B.
  • At 5 years from initiation of ADT, the prostate cancer-specific survival rate was 66.0 percent in Group A and 33.3 percent in Group B
  • A pre-ADT2 serum testosterone level of < 5 ng/dl was an independent factor predicting biochemical progression (hazard ratio [HR] =6.03).

The authors conclude that serum testosterone levels of greater or less than 5 ng/ml may be useful in determining which patients might benefit significantly from the addition of antiandrogen therapy after initial biochemical failure on an LHRH agonist alone.

As far as The “New” Prostate Cancer InfoLink is aware, the addition of an antiandrogen to an LHRH agonist after initial progression on the LHRH agonist has never previously been associated with extended progression-free or overall survival. However — also as far as we are aware — patients have never previously been classified on the basis of their serum testosterone levels in examining such a possibility.

Clearly, this is a very small, retrospective study, and it would be interesting to see whether this effect could be replicated in a retrospective analysis of data from a much larger series of patients (assuming such a series exists). However, it does offer an interesting possibility that may be highly relevant for a subset of patients with advanced and progressive prostate cancer.

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