US study re-examines testosterone therapy in prostate cancer

Thursday, 28 April 2011- Men with low-risk prostate cancer and symptomatic hypogonadism had no evidence of cancer progression during long-term testosterone therapy, according to the results of a small clinical trial conducted by US researchers.

Neither the mean PSA level nor prostate volume changed significantly during testosterone treatment that continued for as long as eight years, reported Dr. Abraham Morgentaler of Beth Israel Deaconess Medical Center in Boston, and colleagues.

Cancer biopsies in two men suggested cancer upgrading, but subsequent biopsy in one patient and radical prostatectomy in the other showed no evidence of progression. The findings support the saturation hypothesis, which postulates that maximal prostate cancer growth occurs with low-level androgen stimulation, and higher levels elicit little or no additional growth, the researchers wrote in the April issue of the Journal of Urology.

"There has been a scare about testosterone for about 70 years that somehow it is a fuel for the fire in prostate cancer," Morgentaler said in an interview. "It's clear that's not the case. This study, although it's small, is the first time anyone has ever bothered to give testosterone and see what's happening in a prostate that has cancer."

Testosterone therapy has several beneficial effects in men with testosterone deficiency, including improvement in fatigue, libido, and sexual function. However, concern about potential stimulatory effects on prostate cancer has limited use of the hormonal therapy, Morgentaler and co-authors noted in the introduction to their findings.

The concern has its origin in observations that androgen deprivation slows prostate cancer progression, as reflected in decreased serum PSA, and that normalisation of testosterone in androgen-deprived men raises PSA levels.

Though modest and circumstantial, the evidence has supported a traditional ban on testosterone therapy in men with a history of prostate cancer. When asked to write a review of the issue several years ago, Morgentaler and his co-authors were stunned to find no published clinical data to support a prohibition of testosterone in men with prostate cancer.

Subsequently, Morgentaler found a single article, published in 1941 by future Nobel Prize winner Charles Huggins and colleague Clarence Hodges of the University of Chicago (Cancer Res. 1941; 1: 293-297). The article detailed the effects of various interventions on acid phosphatase levels in men with metastatic prostate cancer, including three men who received testosterone injections.

Huggins and Hodges reported data for two of the three men, one of whom had been surgically castrated before getting testosterone. "The general idea -- that adding testosterone to an otherwise relatively normal guy with or without prostate cancer will make the cancer grow -- is based on one individual," said Morgentaler.

More recently, results from several small studies have called into question the traditional paradigm of testosterone prohibition in men with prostate cancer. The studies, which collectively involved about 100 men with definitively treated prostate cancer and testosterone deficiency, showed no evidence of biochemical recurrence during treatment with testosterone for as long as 12 years.

With that clinical and scientific background, Morgentaler and co-authors examined the effects of testosterone therapy in 13 men with untreated prostate cancer undergoing active surveillance. The men had a mean age of 59, mean PSA value of 5.5 ng/mL, mean testosterone concentration of 238 ng/mL, and all but one had a biopsy Gleason score of 6 (one patient with Gleason 7).

After a median treatment duration of 2.5 years, the group's testosterone values averaged 664 ng/dL (P<0.001). Mean PSA level declined to 3.6 ng/mL, which did not differ significantly from baseline. Prostate volume also did not change.

The men had an average of two prostate biopsies during follow-up, and 54% of specimens had no evidence of cancer. Limitations of the study included its small size, retrospective design, inclusion of some men who had prostate cancer diagnosed after the start of testosterone therapy, and lack of generalisability to those with higher grade or higher volume disease.

On the basis of the results, the longstanding prohibition against testosterone therapy in men with untreated or low-risk prostate cancer merits re-evaluation, the authors wrote in conclusion. Use of testosterone therapy by prostate cancer patients should be guided by an individual patient's testosterone level and any associated symptoms, said Morgentaler.

"To be a candidate for testosterone therapy, one needs to have symptoms and a low level of testosterone confirmed by blood testing," he said. "In terms of giving it to men with a history of prostate cancer, the main impediment at this point is that there still are no large, long-term studies that can give us the bounds of safety data on this."

Before starting testosterone therapy, each of his patients must sign a consent form that spells out the unknown risks associated with the hormonal therapy, Morgentaler added.

Source. A, Morgentaler, et al "Testosterone therapy in men with untreated prostate cancer," Journal of Urology 2011; DOI:10.1016/.2010.11.084.

 

Edited by: JV


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