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Castrate serum T levels and prostate cancer-specific mortality

Posted Dec 26 2010 12:00am


A few weeks ago, a Letter to the Editor in the New England Journal of Medicine focused on the significance of castrate levels of serum testosterone ( serum T) in men being treated with LHRH agonists for advanced forms of prostate cancer.

The “right” level of serum T in men being treated with androgen deprivation therapy (ADT) has never been categorically established. As Crawford and Rove note in their letter :

  • The target serum T level for men being treated with LHRH agonists and LHRH antagonists as defined by the U.S. Food & Drug Admionistration – is < 50 ng/dl, which is equivalent to 50 μg/ml or 1.7 nmol/l. However, …
  • The typical serrum T level in men after an orchiectomy is 14 ng/dl, which is equivalent to 14 μg/ml or 0.5 nmol/l.

Over the years, there have been many specialists who have argued that the appropriate serum T level for a man who is being well-controlled on ADT should, in fact, be < 20 ng/dl (0.7 nmol/l).

The other key points made by Crawford and Rove in their letter are that:

  • About 85 percent of physicians who treat advanced prostate cancer with ADT do not routinely measure serum T levels at all.
  • Morote et al. have shown that 25 percent of men receiving continuous ADT with an LHRH agonist have a serum T level > 50 ng/dl
  • 44 percent of the same group of men studied by Morote et al. had a serum T level that was consistently < 20 ng/dl (0.7 nmol per liter).
  • Also, in the same group of men, Morote et al. demonstrated a direct correlation between serum T levels and time to development of castration-resistant prostate cancer (CRPC) .
  • Perachino et al. have also reported a significant association between serum T levels 6 months after initiation of ADT and overall survival.

With the rapid evolution of a wide series of new and development-stage drugs for the treatment of advanced prostate cancer, it seems to The “New” Prostate Cancer InfoLink that regular monitoring of serum T levels is now probably obligatory for men receiving continuous ADT. At the same time, we need prospective (as opposed to retrospective) clinical data on the association between serum T levels and prostate cancer-specific mortality. Such data should not be difficult to collect, given the large number of ongoing and upcoming trials on the management of late stage prostate cancer.

If the progression-free, disease-specific, or overall survival of men with advanced prostate cancer who are being treated with ADT is affected by their serum T level while they are on therapy, we need to know this. We also need to appreciate what this implies for men who are on intermittent ADT. Do these men need a serum T of < 20 ng/dl while they are on ADT to allow for their rising serum T while they are off therapy?

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