Testosterone Produces Mixed Results in Prostate Cancer Study

No Increase in Biochemical Recurrence

Nick Mulcahy

July 18, 2013

In men with prostate cancer, the use of transdermal testosterone-replacement therapy (TRT) after radical prostatectomy produced an increase in testosterone levels, but also had the undesirable effect of increasing prostate-specific antigen (PSA) levels.

However, the use of TRT did not appear to increase biochemical recurrence rates during follow-up, which was a median of 27.5 months for treated men, according to a study published in the August issue of the Journal of Urology.

These findings amount to mixed results. But the study authors, led by by Alexander W. Pastuszak, MD, from Scott Department of Urology at the Baylor College of Medicine in Houston, highlight the lack of a higher biochemical recurrence rate in the treatment group, which they call "interesting and potentially significant."

This research adds to the limited literature on TRT in men with prostate cancer. Fewer than 600 men with prostate cancer have been treated with TRT (in a variety of ways) and studied, the authors note.

Their retrospective study involved 153 men who had undergone a radical prostatectomy — 103 who were hypogonadal and were treated with TRT and 50 who were nonhypogonadal.

A diagnosis of hypogonadism, which was made after surgery, was based on the presence of hypogonadal symptoms, including fatigue, insomnia, weight gain, worsening cognition, decreased libido, and/or worsening erectile function and serum testosterone. Even men with normal levels of testosterone (above 300 ng/mL) were treated with testosterone if they had hypogonadal symptoms.

On the basis of the study findings, it is "premature to postulate that TRT in men with a history of prostate cancer may be protective," the authors report.

The use of TRT in prostate cancer is controversial. This stems, in part, from earlier research that established the cancer as "androgen-dependent." Studies in the 1960s and 1970s also found that TRT led to "tumor growth and/or recurrence in patients with metastatic or advanced prostate cancer," they write.

"The landmark study that initially linked testosterone and prostate cancer was done in 3 patients with metastatic prostate cancer in whom castration resulted in regression of the prostate cancer," Dr. Pastuszak told Medscape Medical News in an email.

However, research conducted in the past 10 years has shown that TRT is not associated with prostate cancer recurrence or progression, according to the authors.

They also report that in "several studies" of patients treated with prostatectomy — all involving fewer than 60 men — TRT did not increase the risk for biochemical recurrence or progression. Their results support this.

"In vitro studies have demonstrated that prostate cancer cells respond to testosterone stimulation by growing. However, this does not appear to be the case in the setting of the normal human physiology and in the setting of most prostate cancer," Dr. Pastuszak explained.

The health benefits of TRT have become "more firmly established" and include improved vitality, sexual desire, bone health, and cardiovascular function, the study authors report.

Clinicians who give testosterone to men who have been treated for prostate cancer need to closely monitor these patients, said Wayne J.G. Hellstrom, MD, chief of the section of andrology in the Department of Urology at Tulane University School of Medicine in New Orleans, Louisiana.

"I wait 1 year before starting TRT. Initially, I follow their PSA values every 3 to 4 months for the first year. If no significant change occurs, I move to every 6 months for a year, then annually," he told Medscape Medical News in an email.

Dr. Pastuszak's team used a similar schedule. "We see them every 3 months with regular lab tests, evaluation of their blood counts and PSA, as well as rectal exams in those who have not had their prostates removed," Dr. Pastuszak said.

However, the use of TRT is explicitly discouraged in men with prostate cancer by the Endocrine Society's clinical guidelines on men with androgen-deficiency syndromes. They "recommend against starting testosterone therapy in patients with breast or prostate cancer."

Biochemical Recurrence Rates Similar

In their study, all of the men who received TRT had at least 1 PSA level that was undetectable after radical prostatectomy, Dr. Pastuszak and colleagues report.

In the TRT group, 26 men had high-risk and 77 had low/intermediate (nonhigh)-risk prostate cancer. In the reference group, 15 men had high-risk and 35 had nonhigh-risk prostate cancer.

In the TRT group, there was a small but statistically significant increase in PSA in the high-risk and nonhigh-risk groups beginning 18 to 24 months after TRT initiation. This suggests that "an overall trend toward increasing PSA does occur in men on TRT," the authors note.

In contrast, there was no overall significant increase in PSA in the reference group.

Men in the TRT group had significant increases in serum testosterone levels at almost all follow-up time points, which extended out to 36 months, the authors note.

Biochemical recurrence, defined as consecutive increasing PSA levels and patient referral for salvage radiation therapy, occurred in 4 patients in the TRT group and 8 in the reference group, but the recurrence rates were similar and nonsignificant. Notably, all recurrences in the TRT and reference groups were in high-risk patients.

Dr. Pastuszak has disclosed no relevant financial relationships. Some of his coauthors report financial ties to industry, including Endo and Eli Lily, both of which manufacture TRT.

J Urol. 2013;190:639-644. Abstract

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