Does antiandrogen withdrawal work better in a subset of men on ADT?

A Japanese clinical research group has suggested that antiandrogen withdrawal  after combined androgen blockade may work best in men whose cancer is progressing rapidly after a long period on an LHRH agonist + antiandrogen therapy.

Matsumoto et al. carried out a retrospective chart review of data from 121 of their patients who were initially managed by antiandrogen withdrawal after the failure of combined ADT using and LHRH agonist and an antiandrogen. Since the early 1990s, antiandrogen withdrawal has been a standard “first step” in the management of men receiving combined ADT once it is clear that the patient has a rising PSA and is showing signs of castration resistance. Historically, about 50 percent of such patients will show some degree of response to antiandrogen withdrawal at this stage of progression of their disease.

Here is what Matsumoto et al.  found in a careful analysis of the data from their patients:

  • 35/121 patients (28.9 percent) had a reduction in their serum PSA level after antiandrogen withdrawal.
  • In 16/121 patients (13.2 percent) this reduction in serum PSA levels was > 50 percent of the baseline level.
  • 48/121 patients demonstrated a reduction in their PSA doubling time after antiandrogen withdrawal.
  • A long duration of combined ADT was a significant predictor for a good response to antiandrogen withdrawal.
  • A short baseline PSA doubling time was a significant predictor of low risk for further shortening of PSA doubling time after antiandrogen withdrawal.

After stratification of the patients into four subgroups, the authors were able to further show that patients with a prior duration of combined ADT > 18 months and a PSA doubling time ≤ 3 months demonstrated the best responses to antiandrogen withdrawal, with

  • A response rate (67.9  percent)
  • A low risk for a worsening of their disease (14.3  percent).

It should be recognized that these data are based on a retrospective analysis, and can only be considered as “hypothesis generating” at this time. It will also be evident to many readers that when a man has early castration-resistant disease and a PSA doubling time of ≤ 3 months, any benefits from antiandrogen withdrawal will be limited in their long-term benefit, so the value of this information may also be limited.

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