Testosterone therapy in untreated men with prostate cancer
Posted Mar 17 2011 12:00am
One of the most controversial issues in the management of prostate cancer is whether testosterone therapy can be given to men who have or are at risk for the recurrence of this type of cancer. Such use of testosterone therapy has been contraindicated for many years, but recent data has started to question this longstanding contraindication (which is based on the belief that high serum testosterone levels in men with prostate cancer are associated with more rapid rates of prostate cancer growth).
Morganthaler et al. have now and we believe for the first time reported data from a small series of symptomatic, testosterone-deficient men who received testosterone therapy while undergoing active surveillance for prostate cancer.
Here are their core findings:
13 symptomatic, testosterone-deficient men with untreated prostate cancer received testosterone therapy for an average (median) of 2.5 years (range, 1.0 to 8.1 years).
The average (mean) age of the patients was 58.8 years.
The Gleason scores of the patients at initial biopsy were either 6 (in 12/13 men) or 7 (in 1/13 men).
Among the 13 men, the average (mean) concentration of total serum testosterone increased from 238 to 664 ng/dl over time.
The average (mean) PSA levels of the patients actually fell over time (from 5.5 ± 6.4 ng/ml before initiation of testosterone therapy to 3.6 ± 2.6 ng/ml after treatment).
Prostate volume among the subjects was unchanged.
Patients received an average of two follow-up biopsies.
No local prostate cancer progression or distant disease was observed.
Morganthaler and his colleagues conclude that testosterone therapy in these symptomatic, testosterone-deficient men with untreated prostate cancer was not associated with prostate cancer progression in the short to medium term. And that is a fair conclusion.
They go on to argue that, “The longstanding prohibition against testosterone therapy in men with untreated or low-risk prostate cancer or treated prostate cancer without evidence of metastatic or recurrent disease merits reevaluation.” That will be a harder pill for most urologic oncologists to swallow but see the reference below to the new article by Coward and Carson.
The fly in the ointment here is that the patients Morganthaler et al. were treating with testosterone were men with a natural testosterone deficiency. In other words, their normal testosterone processing capabilities were less effective than those of “normal” males. It may well be, therefore, that even though it was possible to raise the serum testosterone levels of these patients, this could be done without raising their risk for prostate cancer progression. Whether that would be true for men who have prostate cancer and who process testosterone normally is still unknown.
The real question here is how we effectively address the underlying question of whether it is the serum testosterone level that actually affects prostate cancer or the testosterone level in the prostate (and the processes by which that testosterone is converted to dihydrotestosterone), which really drives prostate cancer growth. Morganthaler and his colleagues have argued for some time that maximal prostate cancer growth is achieved at low androgen concentrations. Their results in this study are consistent with that hypothesis. However, on their own, these data do not prove the validity of that hypothesis.
A detailed review of the entire subject of testosterone replacement therapy for men with prostate cancer has just been published by Coward and Carson. The entire text of this article is available on line for the interested reader. It may be of particular value to support group leaders. This review is supportive of the use of testosterone replacement therapy in men who have been successfully treated for localized prostate cancer and who have a testosterone level of < 300 ng/dl. The authors currently monitor their patients for a minimum of 6 months after first-line treatment for prostate cancer before considering the initiation of testosterone supplementation.