What is the appropriate serum T threshold for medical “castration”?

For many years, the formal threshold level of serum testosterone (T) used to define medical “castration” has been < 50 ng/dl. However, it is widely recognized that this level is probably not low enough to accurately define a medically castrate state.

Since the late 1990s, a variety of working groups have studied available data in an attempt to establish a more appropriate threshold level of serum T to define medically castrate status. In a detailed review published in 2009, Gomella argued that the most appropriate level was < 20 ng/dl, noting that in men who underwent true surgical castration (bilateral orchiectomy), serum T levels normally fell to < 15 ng/ml within a few hours after surgery.

However, a newly published article by Dason et al. suggests, on the basis of data from a small, prospective case series of men, treated between 2006 and 2011 at a tertiary cancer center in Canada with either an LHRH agonist or an LHRH antagonist, that the most appropriate level may actually be < 32 ng/dl.

Dason et al. measured serum testosterone levels every 3 months in a total of 32 patients being treated with ADT. They excluded all patients whose serum T level was > 50 ng/ml. They stratified the patients into two groups:

  • Group A comprised men whose mean serum T level was < 20 ng/ml.
  • Group B comprised men whose mean serum T level was < 32 ng/ml.

Then they followed these men over time until the patrients had castrate-resistant prostate cancer (CRPC), and here are their findings:

  • Average (mean) patient follow-up was 25.7 months.
  • Median progression-free survival times (i.e., times to CRPC)  were
    • 33.1 months for men with a serum T level < 32 ng/dl after 9 months on ADT
    • 12.5 months for men with a serum T level of 32 to 50 ng/ml after 9 months on ADT
    • This difference was statistically significant (p = 0.001)
  • Median times to CRPC were
    • 33.1 months for men with a first-year serum T level of < 32 ng/dl
    • 12.5 months for men with a first-year serum T level of > 32 ng/dl
    • This difference was also statistically significant (p = 0.05)
  • A serum T level of < 20 ng/dl (compared to a serum T level of 20 to 50 ng/dl) did not significantly predict any further reduction in median time to CRPC.

The authors conclude that their study does indeed support a lower serum T threshold (i.e., a serum T level of < 32 ng/dl) to define optimal medical castration as compared to the older standard of < 50 ng/dl. They add that,

Testosterone levels during ADT serve as an early predictor of disease progression and thus should be measured in conjunction with prostate-specific antigen.

It should be noted that this is a small study. It would be helpful to see such data being measured consistently in the context of a larger, randomized, controlled clinical trial so that we could confirm (among several hundred patients) the data presented by Dason et al. In the interim, it is certainly clear that a new standard needs to be established, and it appears to be very clear to The “New” Prostate Cancer InfoLink that measurement of serum T levels based on a standard procedure should be as routine as the measurement of PSA levels in men being treated with any form of ADT.

3 Responses

  1. Medical Oncologist Stephen Strum, well known as a specialist specifically in research and treatment of recurring and advanced prostate cancer, often remarks that one’s testosterone level should be at least < 32 ng/dl, but preferably near or below 20 ng/dl.

  2. The same level of clinically significant threshold for T (< 32 ng/dl) was discussed in an article by Morote et al. in Journal of Urology (see “Redefining clinically significant castration levels in patients with prostate cancer receiving continuous androgen deprivation therapy“).

  3. This was a small study, and the authors themselves do not consider it to have been definitive. Of 32 men who achieved T levels of < 32 ng/dl, 18 got to < 20, and 14 were in the range between. The authors say in their Conclusion: "Both direct and indirect evidence make it clear that there is a need for larger prospective studies involving the measurement of testosterone levels during ADT."

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