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Testosterone therapy did not increase prostate cancer risk in hypogonadal men
Hypogonadal men treated with testosterone therapy are not at increased risk for prostate cancer, according to research published in The Journal of Urology.
Ahmad Haider, MD, PhD, a urologist in Bremerhaven, Germany, and colleagues said testosterone treatment is safe in hypogonadal men if therapy guidelines are properly applied.
“These data suggest that treatment with testosterone does not increase the risk of prostate cancer and support previous arguments that place the fear of testosterone therapy and prostate cancer in a more rational perspective,” the researchers wrote.
The investigators analyzed data from 1,023 hypogonadal men who received testosterone therapy in three parallel, prospective, ongoing, cumulative registry studies. Two study cohorts (mean baseline age, 58 years) were treated by urologists since 2004, and one study cohort (mean baseline age, 41 years) was treated at an academic andrology center since 1996.
The men were treated when total testosterone was ≤12.1 nmol/L and symptoms of hypogonadism were present; testosterone undecanoate injections were administered in 12-week intervals. The median follow-up was 5 years and the maximum 17 years.
Examination of the prostate prior to treatment and monitoring during were performed; prostate biopsies were performed according to European Association of Urology guidelines.
The researchers assessed the amount of positive and negative biopsies and studied the incidence of prostate cancer and post-prostatectomy outcomes.
In the two urology settings, 11 patients were diagnosed with prostate cancer at proportions of 2.3% and 1.5%, respectively; incidence per 10,000 patient-years was 54.4 and 30.7, respectively. The andrology center reported no prostate cancer.
The investigators acknowledged inherent limitations in the registry study design, which lacked a control group, but noted the findings were compelling in the context of general screenings.
“The findings from these three independent registries with more than 1,000 patients treated for a median follow-up of 5 years with testosterone revealed an incidence of prostate cancer less than that detected in general screening trials,” the researchers wrote. “In the combined cohorts the incidence of prostate cancer was 1.08%, which is lower than that reported by [the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial] (7.35%) and [European Randomized Study of Screening for Prostate Cancer] (9.6%), respectively.”
Disclosure: The researchers report financial interest and/or other relationships with Astellas, Bayer Healthcare, Bayer Pharma AG, Clarus, Eli Lilly, Ferring Arzneimittel, GlaxoSmithKline, Jenapharm, Kade/Besins, Takeda and Teva.
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The study by Haider and colleagues provides invaluable real-world confirmation that testosterone therapy does not increase the risk of developing prostate cancer. Rates of cancer in more than 1,000 treated men followed for a median of 5 years, with the longest follow-up 17 years, were lower than reported rates in large populations.
It has taken many years, and many studies, to de-fang the long-held but unfounded belief that increasing serum testosterone causes de novo prostate cancer, or causes occult prostate cancer to grow rapidly. Hopefully, this study will provide additional reassurance for clinicians that have been hesitant to treat hypogonadal men due to fears of adverse events.
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In these men (age range, 15 to 84 years), 92 biopsies were done and 11 were positive for prostate cancer. Based on these data, the “rate” of prostate cancer was calculated as 1.08% among the 1,023-person cohort. This rate was contrasted with rates of 7.35% in the Prostate, Lung, Colorectal and Ovarian (PLCO) trial and 9.6% in the European Randomized Study of Screening for Prostate Cancer (ERSPC) trial. This led the authors to conclude, with caution, that testosterone does not increase the risk for prostate cancer in hypogonadal men.
Although this may be true and these data certainly are consistent with that hypothesis, this reviewer suggests that caution is still justified when considering such testosterone replacement. Among the two largest concerns from this analysis are that the ages of the men studied in the registries (15 to 84 years), as the authors pointed out, are quite different from the ages of men in the PLCO and ERSPC studies. In the latter two trials, entry criteria required that men be aged older than 55 years or 50 years, respectively. There is no doubt that these age differences could substantially modify “expected” rates of prostate cancer in these registries. No data are provided regarding the numbers of men in each decade of life in the registries, though mean ages were 59.53 ± 8.35, 57.37 ± 7.04 and 41 ± 12 years, respectively.
Secondly, follow-up is short. Although some men were followed for as long as 17 years in the registries, the median follow-up was 5 years. In the history of prostate cancer, this is a short time. Additionally, this analysis suffers from the unavoidable problems of any registry trial. Although individuals were considered “adherent,” given the small number of prostate cancer cases found and biopsies performed in these single-arm, essentially retrospective and relatively small series, the possibility for small frequencies of nonadherence to have large effects is real. Consequently, this reviewer would agree that this analysis provides some reassurance that testosterone replacement may be safe; it would be premature in my view to declare the answer “in.”
Considerable caution is still warranted, and careful counseling of individuals is indicated. It is clear that testosterone is the primary contributing factor to the genesis of prostate cancer in the average man. Testosterone signaling is of paramount importance — so restoring/enhancing such signaling by providing testosterone replacement in a manner that does not mirror normal testosterone secretion should be viewed with caution.