Assessment of serum T levels in men on androgen deprivation therapy

A paper in a forthcoming issue of European Urology recommends strongly that clinicians should monitor serum testosterone (serum T) levels during androgen-deprivation therapy (ADT) in men with prostate cancer.

While there are few data to suggest that serum T levels — alone or in combination with PSA levels — are associated with risk for prostate cancer, there have long been recommendations from some clinicians that regular assessment of serum T levels is highly relevant to knowing the effectiveness of ADT in men with progressive forms of prostate cancer. Indeed some have gone so far as to suggest that timing of hormonal treatment should be directly linked to serum T levels in a form of intermittent ADT, with dosing of ADT being based on whether the patient’s serum T level is being maintained below a specific cut-point (castrate level).

Originally, a castrate level of serum T was considered to be < 50 ng/dl (nanograms per deciliter). However, in more recent times a truer castrate level of serum T has been considered to be < 20 ng/dl, and that a serum T level of 50 ng/dl should be considered a cut-point for clear indication that a patient is no longer castrate. Assessment of serum T levels today should be based on mass-spectrometry assays and not on automatic immunoassays because the latter are not suitable for use in men on ADT.

Based on an expert roundtable held in May 2009, Schulman et al. have reviewed published data on the clinical applications of testosterone measurement in screening, diagnosis, and treatment of prostate cancer patients — and the full text of this paper is available on line.

The authors reached consensus on a series of recommendations:

  • Serum T measurement should not be used to determine risk for prostate cancer in the general population.
  • Serum T measurement can not be recommended to increase the specificity of PSA testing or to determine the aggressiveness of prostate cancer.
  • When ADT is initiated, serum T should be regularly checked (alongside serum PSA levels) to ensure adequate response to ADT.
    • If castrate levels of serum T are achieved on the first three determinations, testosterone monitoring may be ceased or reduced in frequency.
    • Patients not achieving castrate levels require further monitoring, with change in therapy considered if serum T levels are persistently elevated above castrate levels.
  • If PSA levels rise while a patient is on ADT, castrate levels of serum T should be demonstrated before castration resistance is assumed.
  • Serum T levels might be considered as a criterion for reinitiating ADT in patients receiving intermittent ADT, and should be further evaluated in this context.

These recommendations appear to offer a sensible compromise between ignoring serum T levels entirely (at the one end) and linking ADT directly to serum T levels on an ongoing basis (at the other).

Now we should be clear (as are the authors) that this paper is based primarily on  “expert opinion” rather than on a rigorous, evidence-based review of the literature. The “New” Prostate Cancer InfoLink would like to see clinical studies carried out that could be used to substantiate these recommendations, but that may be too much to hope for, given the widely ingrained habits and beliefs of many in the urologic oncology community.

It should also be noted that funding for the expert roundtable and development of this paper was provided by a pharmaceutical company — but since that pharmaceutical company is not in the business of selling testosterone tests, we do not see any particular conflict of interest here.

2 Responses

  1. I am now a veteran of monitoring my intermittent triple androgen deprivation therapy (Lupron, Casodex 50 mg, finasteride 5 mg x2, plus a bisphosphonate/calcium/vitamin D3 and nutrition/diet/supplements, exercise, and stress reduction in support) since 2000. I’ve been closely following the recommendations of doctors who are convinced that monitoring testosterone AND DHT is key to effective management of ADT.

    These recommendations should help advance the state of practice. I particularly like the recognition that the threshold for effective testosterone suppression should be <20 instead of <50. However, there is probably plenty of inertia in the system and that could slow change. Two years ago I served as a "consumer reviewer" (aka survivor representative) on a panel of researchers and physicians reviewing prostate cancer research proposals for the Congressionally Directed Medical Research Program. More than one proposal related to androgen deprivation, and the threshold of <50 was used in the proposal. I objected that that was a weak point, as <20 was the threshold used by experts. However, the panel’s consensus was that <50 was still standard, and that did seem to be the case, unfortunately. Hopefully, that will change.

    By the way, my own testosterone has been below 20 on two of my three completed cycles of triple therapy, the first and third, but was right about 20 for the second, even though my PSA declined to <0.01 for the first and second cycles, and to 0.04 as the nadir for the third, which I just completed.

    The recommendations look for a change in therapy if testosterone is "persistently" above castrate levels. I'll bet the docs I follow would not be so patient; instead, they would look for flaws in administration or storage of the LHRH-agonist drug, or for whether the coil popped out for Zoladex, or for unusually rapid clearance by the particular patient, in which case they would decrease the dosing interval.

    I'm curious why they did not look at DHT monitoring as well. Apparently it can remain high in some of us in spite of very low testosterone.

    I'm kind of doubtful that monitoring testosterone during the off-therapy period will be useful.

  2. Since testosterone is expected to rise while on intermittent androgen deprivation (IAD), the explanation “Serum T levels might be considered as a criterion for reinitiating ADT in patients receiving intermittent ADT, and should be further evaluated in this context” is not understood. Return to active ADT while on IAD is based on a rising PSA level, not on a testosterone level whether high or low. I would see more concern for considering reinitiating ADT if one’s dihydrotestosterone (DHT) level were near or over 30 ng/dl.

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