Study: More evidence of T therapy’s safety in some PCa patients

November 7, 2016

Testosterone therapy in hypogonadal men with prostate cancer who have had definitive treatment and in those on surveillance appears to be safe, according to a new study.

Testosterone therapy in hypogonadal prostate cancer patients who have had definitive treatment and in those on active surveillance appears to be safe, according to a new study.

Urologists and others have been cautious about using testosterone therapy in men with prostate cancer since the early 1940s, when Huggins et al published research suggesting reductions in testosterone caused metastatic prostate cancer to regress, while exogenous testosterone administration caused the cancer to grow (Arch Surg 1941; 43:209-23). But studies in the last 20 years, including a historical perspective by Abraham Morgentaler, MD, published in 2006, suggest the association is a myth and there is no scientific basis for thinking testosterone causes prostate cancer to grow (Eur Urol 2006; 50:935-9).

In this new study, published in the Journal of Urology (2016; 196:1082-9), Canadian and Australian researchers found similar results. They studied 82 hypogonadal prostate cancer patients treated with testosterone therapy. Among the subjects, 50 men had received radiation therapy, 22 had radical prostatectomy, eight were on active surveillance, one had cryotherapy, and one was treated with high-intensity focused ultrasound.

In a median 41-month follow-up, they found increases in testosterone and PSA levels among all the prostate cancer patients on testosterone therapy. PSA increased among active surveillance patients, but none were upgraded to higher Gleason scores, nor had they progressed to definitive treatment. While none of the radical prostatectomy patients experienced biochemical recurrence, three of the radiotherapy patients did. Whether those cases of biochemical recurrence resulted from testosterone therapy or the natural disease course is unclear, the authors write.

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The authors report PSA velocity was 0.001 ug/L/yr in the radical prostatectomy group, 0.12 ug/L/yr in the radiotherapy group, and 1.1 ug/L/yr among those on active surveillance.

Next: Dr. Ory discusses study results

 

Still, while the evidence points to a change in the current treatment approach, the authors note their trial is not randomized or placebo-controlled and is retrospective. If future randomized, controlled trials confirm these and other results, urologists might feel more comfortable using testosterone therapy in hypogonadal men with treated prostate cancer or men on active surveillance.

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Lead author Jesse Ory, MD, of Dalhousie University, Halifax, Nova Scotia, says that he has seen urologists take a mix of approaches regarding the use of testosterone therapy in men after prostate cancer.

“Some urologists are hesitant to prescribe testosterone therapy to men with treated prostate cancer and are waiting for data from a prospective, randomized, controlled trial before making any definitive choices on the matter. This approach is understandable, given the lack of level 1 evidence,” he said.

“However, the majority of the urologic oncologists I have worked with do practice a cautious, measured approach to the matter, based on the existing evidence. In patients with symptoms of hypogonadism and a low serum testosterone, who have been treated for prostate cancer and have an undetectable or stable PSA (often for at least 6 months), the subject is broached,” added Dr. Ory, who worked on the study with S. Larry Goldenberg, MD, and co-authors.

Dr. Ory says initial patient visits involve an open discussion about the risks and benefits of testosterone in this context and the need for closely monitored therapy. The patient subgroups whom urologists seem the most comfortable treating with testosterone therapy are those with an undetectable or stable PSA after radical prostatectomy or radiation therapy, followed by those on active surveillance, according to Dr. Ory. Extreme caution is used in men at a high risk of recurrence or progression.

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“The low numbers of patients studied on active surveillance, as well as the presence of active prostate cancer cells in situ makes many nervous,” he said. “I suspect this will only dramatically change once we have prospective, randomized, controlled trials to support the many retrospective studies done thus far.”

Next: The most surprising finding in the study

 

The most surprising finding in this study for Dr. Ory and colleagues was the lower incidence of biochemical recurrence compared to the rates seen in larger trials.

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“After looking into this further, there is some very early biochemical research that may suggest that being eugonadal is the most ‘protective’ for the prostate and slows growth of any active prostate cancer versus being hypogonadal,” he said, citing a study in the Asian Journal of Andrology (2016; 16:864-8). “This is very preliminary data, but it hints at an interesting future. Perhaps after treatment for prostate cancer, adding testosterone to ensure men are in a eugonadal state may confer a higher progression-free survival rate versus leaving them with low T. It's much too early to tell but would be a dramatic paradigm shift if true.”

The difference in biochemical recurrence, while interesting, should be viewed with caution, according to Dr. Ory.

“First of all, our average follow-up time is 41 months, which is less than what was done in [other studies]. This limits direct comparison,” he said. “Secondly, one could reasonably argue that our N is too small to expect to see a similar trend. These are valid criticisms, yet do not discount the findings entirely.”

At this point, the safest approach is a cautious, individualized approach, Dr. Ory says.

“In those who want to offer a trial of therapy, the body of research on this topic should be grounds to reassure our colleagues that testosterone therapy in this population is reasonable and safe. They should be reassured by over a dozen studies done to this point: All have either showed an equal or lower rate of biochemical recurrence, with no trials showing increased risk,” he said.

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