Data: May Be OK to Give 'T' to Men With Prostate Cancer

Nick Mulcahy

September 22, 2016

Clinicians may be able to safely give testosterone therapy to hypogonadal men who have been treated for prostate cancer or are on active surveillance for the disease, according to a study of a cohort of Canadian and Australian men.

In other words, it appears okay to give testosterone, or T, as it is commonly called, to men with prostate cancer, say the researchers, led by Jesse Ory, MD, a urologist at the University of British Columbia in Vancouver, Canada.

The finding goes against a long-held belief that testosterone would be harmful, as the hormone has been linked to the growth fo prostate cancer in studies that date from the 1940s. Indeed, a main treatment for prostate cancer – androgen deprivation therapy – aims to block testeosterone.

The idea of giving testosterone to men with prostate cancer has come about as more contemporary research, including other cohort studies, questioned this long-standing prohibition, the authors point out in the new study, which was published in the October issue of the Journal of Urology.

Testosterone supplementation for older men is controversial but popular in the United States. Testosterone deficiency, which is also called hypogonadism, increases in prevalence as men age, the authors point out.

The symptoms of the deficiency, which occurs in about 1 in 5 men older than 70, include decreased muscle mass, increased body fat and weight, low sex drive, and fatigue. Testosterone supplementation has been shown to improve symptoms.

The researchers note that there are no clinical trial results to guide clinicians in the use of testosterone supplementation in men with prostate cancer. To obtain data in this setting, they identified 82 hypogonadal men with prostate cancer who were treated with testosterone therapy at Vancouver General Hospital in Canada and Victoria General Hospital in Melbourne, Australia.

The median age of the patients was 75.5 years, and the median follow-up was 41 months. The researchers found an overall increase in levels of testosterone (P < .001) and prostate-specific antigen (PSA) (P < .001) in the entire cohort, including those on active surveillance. Importantly, no patients were upgraded to a higher Gleason score on subsequent biopsies, and none went on to have definitive treatment for prostate cancer.

Three men in the cohort (6%) experienced biochemical recurrence, but it is unclear whether these cases were related to testosterone supplementation or disease biology.

The rate of biochemical recurrence is lower than clinical norms, say the authors.

The patients in the study included 50 men treated with radiotherpy, 22 treated with radical prostatectomy, eight on active surveillance, one treated with cryotherapy, and one who underwent high-intensity focused ultrasound.

The mean PSA velocity in the radical prostatectomy, radiation therapy, and active surveillance groups were 0.001, 0.12, and 1.1 mg/L per year, respectively.

Overall, the PSA findings are similar to what is currently seen in the literature, say the researchers.

Testosterone therapy may be oncologically safe. Dr Jesse Ory and colleagues

The findings led the Dr Ory and his coauthors to conclude that "testosterone therapy may be oncologically safe" in this setting.

The authors also point out that several clinical trials involving testosterone therapy are in progress, including a randomized study of testosterone replacement in patients with low-risk hormone-refractory prostate cancer.

The results from these trials "could lead to a change in our current treatment approach," the authors acknowledge.

In the meantime, the use of testosterone therapy among hypogonadal men with treated prostate cancer or on surveillance "should be monitored closely with serial PSA measurements and involve a detailed discussion of the potential risks and benefits with the patient prior to initiation of therapy," they write.

History Lesson

The idea that using testosterone therapy in men with prostate cancer may be oncologically safe is in part an outgrowth of a theory known as the "saturation model," say the authors. According to that theory, testosterone exerts its maximal effect on androgen receptors and prostate cancer growth at low concentrations but has little to no impact at higher concentrations.

However, in an editorial in the same issue of the Journal of Urology, a pair of Canadian experts say that testosterone therapy may "promote prostate cancer progression" and cannot be given without emphasizing that.

The androgen receptor is a "driver" in prostate cancer, say Martin E. Gleave, MD, a urologist at the University of British Columbia in Vancouver, and Laurence Klotz, MD, a urologist at the Sunnybrook Health Sciences Center, University of Toronto.

Testosterone therapy is a "reasonable option" for symptomatic men with low testosterone levels who do not have prostate cancer (and are at low risk for the cancer), they write.

But there is "an onus on testosterone replacement therapy proponents" to robustly demonstrate safety with regard to prostate cancer risk.

"There is a plethora of low-level evidence from many small trials," they write, referring to studies such as the current cohort of 82 men. But underpowered studies cannot detect small but clinically meaningful harm from an intervention, they add.

There is also a history here, related to industry overplaying evidence, that clinicians can learn from, say Dr Gleave and Dr Klotz.

"HRT [hormone replacement therapy] in women is an apt cautionary tale, as the increased breast cancer and cardiovascular risks required larger studies to be demonstrated," they write.

One of the study authors has a financial interest with Genyous. The other authors and the editorialists have disclosed no relevant financial relationships.

J Urol. 2016;196:1082-1089. Full text, Editorial

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