Long-term 'T' Does Not Up Risk for High-grade Prostate Cancer

Nick Mulcahy

November 25, 2015

Testosterone replacement therapy taken for up to 5 years is not associated with an increase in the risk that older men will develop high-grade prostate cancer, according to a study with more than 50,000 men with prostate cancer.

The results were published in the December issue of the Journal of Urology.

This study extends the length of time testosterone therapy, commonly known as T, has been studied in men who are subsequently diagnosed high-grade disease, explain the authors, led by Jacques Baillargeon, MD, from the University of Texas Medical Branch in Galveston.

"To date only one population-based study has been done to examine whether exposure to testosterone therapy increases the risk of high-grade prostate cancer," they write, referring to an analysis that examined up to 1 year of testosterone therapy use before a diagnosis of prostate cancer (Urology. 2013;82:321-326).

With only a 1-year study in the medical literature, Dr. Baillargeon and his coauthors say that their "long-term" study of 5 years "offers novel and clinically relevant information to clinicians."

The extended time period is important because of the "slow growth of prostate cancer and the unknown latency period associated with testosterone exposure," they note.

Five years is a good length for this kind of retrospective data, Dr. Baillargeon explained.

The time that might fully cover the incubation period of prostate cancer — which is 15 years or so — would not be practical, he said. "When you require that kind of look-back period, you restrict your study sample a great deal," Dr. Baillargeon told Medscape Medical News. Men in a major database would have to be selected at 80 years of age and older to generate 15 years of treatment history, he said.

Other studies looking at various durations of use have shown that there is no significant association between the overall incidence of prostate cancer and testosterone therapy. But these studies have not focused on the most worrisome type of early-stage prostate cancer: high-grade disease.

For their study, Dr. Baillargeon and his team used Surveillance, Epidemiology and End Results (SEER)–Medicare linked data to identify 52,519 men diagnosed with incident prostate cancer from 2001 to 2006 who had at least of 5 years continuous enrollment in Medicare before their diagnosis and who met the study criteria.

The therapy was limited to injectable forms of testosterone, which was the only type that Medicare data captured at the time. High-grade disease was indicated by a Gleason score of 8 to 10.

In the study cohort, 574 men had used testosterone in the 5 years before diagnosis and 51,945 has not. The incidence of high-grade prostate cancer was 20.1% in the testosterone users and 27.0% in the nonusers.

After adjustment for demographic and clinical characteristics, exposure to testosterone therapy was not associated with an increased risk for high-grade prostate cancer (odds ratio [OR], 0.84; 95% confidence interval [CI], 0.67 - 1.05).

Importantly, the risk for high-grade disease did not increase as the number of testosterone injections increased (OR, 1.00; 95% CI, 0.98 - 1.01). This finding is a first in the literature, the authors report.

"No Clear Signal"

The results are heartening, a pair of experts suggests in an accompanying editorial.

"The authors found no clear signal that testosterone replacement therapy in this large population had any negative effect on the frequency of high-grade prostate cancer," write Culley C. Carson III, MD, from the University of North Carolina at Chapel Hill, and Roger Kirby, MD, from The Prostate Center in London, United Kingdom.

The editorialists explain why testosterone replacement therapy is unlikely to spur the development of prostate cancer.

Multiple prostate-specific antigen (PSA) studies of men taking testosterone replacement therapy have shown "only modest PSA increases and then usually in those with the lowest initial testosterone," they write.

The "saturation model" theory of testosterone and prostate cancer can explain this phenomenon, they add.

"The theory states that while prostate cancer is exquisitely testosterone sensitive at low testosterone levels, after androgen receptors are fully occupied further, testosterone does little to change prostate or prostate cancer dynamics," Drs Carson and Kirby write.

Another expert explained the saturation model using different terms earlier this year at the American Urology Association annual meeting.

At one time, the conventional wisdom in urology was that "prostate cancer was fire and testosterone was gasoline," said Tobias Köhler, MD, MPH, from the Southern Illinois University School of Medicine in Carbondale.

But a better analogy, he said, is that prostate cancer is a tree and testosterone is water. "You need a certain amount of testosterone for prostate cancer to develop, but if you keep piling on more and more testosterone [water], the tree doesn't develop into a sequoia," he explained.

This phenomenon means that it is likely safe to give testosterone therapy to men who already have prostate cancer, the editorialists point out.

"While more data are needed, healthcare providers can begin to consider treating hypogonadal patients who have prostate cancer with testosterone replacement therapy if they are symptomatic, have documented low testosterone, and are properly informed," they write.

Dr Baillargeon, his coauthors, Dr Carson, and Dr Kirby have disclosed no relevant financial relationships.

J Urol. 2015;194:1527-1528, 1612-1616. Editorial, Abstract


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