Pilot Study Eases Fears Over Testosterone in Advanced Prostate Cancer

Caroline Helwick

October 30, 2017

SAN ANTONIO — A small pilot study delivered a big message about the use of testosterone in men with advanced or metastatic prostate cancer, according to a "Best Abstract" presented at the Sexual Medicine Society of North America (SMSNA) Fall 2017 Scientific Meeting.

Testosterone therapy greatly improved quality of life in all the patients, without triggering the kind of complications that have made this treatment taboo for decades, reported Abraham Morgentaler, MD, director of Men's Health Boston at Beth Israel Deaconess Medical Center in Massachusetts. The study's first author was Yonah Krakowsky, MD, from the University of Toronto, Ontario, Canada.

"We have all been told you can never do this. That terrible things will happen quickly. That patients will be paralyzed or die," Dr Morgentaler told Medscape Medical News. "I'm not advocating that we give testosterone therapy to all men with advanced prostate cancer. But I think there is room for us to deviate a little bit from our historical idea that testosterone is bad in all cases."

While recognizing the potential risks of this practice and signing informed consent, seven men with advanced prostate cancer who had previously received androgen deprivation therapy (ADT) were given testosterone for up to 7 years. All experienced improvements in vitality, strength, sexual desire, and function, and none had a "precipitous progression or unexpected complication" during treatment, he reported at the meeting.

"What we did not see is maybe what's most important, and that was no vertebral collapse, spinal compression, or acute death. On the contrary, these men expressed gratitude for the opportunity to live a more satisfying and full life. They thanked us for our willingness to offer them a treatment that every other doctor said was going to kill them," he said. 

These 7 men were drawn from a larger study of 202 "all-comers" with prostate cancer who received testosterone therapy in his practice. After 47 months' median follow-up, no evidence of increased recurrence or progression risk was observed. Recurrence/progression rates were consistent with published rates for the various forms of prostate cancer treatments: 6.5% after radical prostatectomy, 2.0% after radiotherapy, 67% after high-intensity focused ultrasonography (2 of 3 patients), and 3.5% after active surveillance, the researchers reported at the meeting. 

Experience Contradicts Conventional Wisdom

John Mulhall, MD, from Memorial Sloan Kettering Cancer Center, New York City, called the findings in the patients with advanced prostate cancer "fantastic" but pointed out that they fly in the face of many published reports. "We have all this literature on the topic. Should we just ignore it?" he questioned.

"No, but I would say we have misunderstand those older data," Dr Morgentaler responded. He noted that there are differences between his patient population and those discussed in the bulk of the literature and that this can make a significant difference.

Rationale for Pilot Study

Testosterone therapy has been contraindicated for decades in men with a history of prostate cancer because of fears that it will "add fuel to the fire," he said. But recent favorable experiences in men after treatment with radical prostatectomy, radiation therapies, and even active surveillance have sparked a major re-evaluation of this contraindication.

Dr Morgentaler said he has been particularly "emboldened" by positive reports with "bipolar" androgen therapy, in which the body is alternately flooded with and starved of testosterone. Castration-resistant patients receive a high dose of testosterone every 28 days while also receiving luteinizing hormone–releasing hormone (LHRH) therapy. In addition to symptomatic improvement, tumor shrinkage has been observed along with declines in prostate-specific antigen (PSA), researchers from Johns Hopkins University in Baltimore, Maryland, have reported.

Although such studies suggest testosterone might actually have some therapeutic benefit, Dr Morgentaler's goal has been different: to help select patients who report being "miserable" on or after ADT live "better," not necessarily "longer."

Study Details

The seven men with advanced/metastatic prostate cancer, identified through a retrospective chart review, were treated with testosterone therapy between 2005 and 2016. Electronic records were reviewed for baseline characteristics, additional treatments, outcomes, and qualitative responses that were documented from patient communication. All men provided signed informed consent,  which indicated that the treatment may hasten disease progression and death.

All had symptoms characteristic of testosterone deficiency, including decreased sexual desire and function, decreased energy, fatigue, and impaired cognition. Average age was 69 years (range, 54 to 94 years). Pathology was a Gleason score of 7 to 9. Median PSA at initiation of testosterone was 2.1 ng/mL (range, 0 to 546 ng/mL). Five men presented with biochemical recurrence after definitive local treatment with radical prostatectomy or radiation. Four men presented with asymptomatic bone metastases.

Six of seven (86%) had previously undergone at least one injection of LHRH agonist or antagonist and discontinued it. One declined ADT despite the presence of bone metastases. Treatment consisted of injections, pellets, and/or topical forms of testosterone. Median treatment duration was 30 months; one patient received testosterone for 84 months.

Safe and Beneficial in All Men

All patients reported symptomatic benefits, including improved energy, cognition, libido, sexual function, and sense of well-being. There were no cases of disease flare, acute pain, or vertebral collapse.

One patient with an obstructed ureter and nephrostomy tube was able to have sex for the first time in 3 years. Another man was able to demolish his outdoor deck when his contractor failed to show up. "He was thrilled because he had been weak for years. This is who he used to be," Dr Morgentaler commented.  

Three patients are continuing on testosterone; two discontinued once PSA rose above 20 ng/mL; and two died of causes not related to prostate cancer. The rise in PSA may well be a manifestation of the disease course, but "it made us nervous," he acknowledged.

Dr Morgentaler said that on the basis of these encouraging findings, "we will start looking at this in a more careful way going forward." He hopes that the results of the pilot study, and the larger study in mostly earlier-stage disease, will shift the thinking about testosterone in patients with prostate cancer. "Until recently, men with testosterone deficiency were unable to experience the benefits of testosterone therapy if they had any prior history of prostate cancer, even if cured. These results suggest there may no longer be a need to continue this prohibition, particularly in men with low-risk disease."

Uncertainty Still Exists

Faysal A. Yafi, MD, director of men's health at the University of California Irvine, commented that "this is obviously a very contentious topic" that is being turned on its head by a "trailblazer in the field of testosterone therapy, particularly in prostate cancer."

Dr Yafi explained that the use of testosterone replacement in earlier-stage prostate cancer is not as controversial because there are "little to no data" suggesting testosterone is likely to increase the risk for prostate cancer. "Many urologists today will give testosterone replacement to men with low- and intermediate-risk, treated or untreated, prostate cancer in certain settings," he said.

However, the concerns about testosterone in men with metastatic prostate cancer are not likely to dissipate overnight. The effect of the hormone in this setting are unclear; clinicians will continue to fear the potential for the "flare of cancer" and "serious complications," and patients who choose to get testosterone may forego other new "life-prolonging" options now available for prostate cancer, he said.

On the other hand, Dr Yafi acknowledged that testosterone could have benefits in patients with advanced prostate cancer. "These men are usually quite weak and frail, and testosterone may improve their quality of life."

Dr Morganteler disclosed financial relationships with Aytu, Acerus, Antares, Bayer, and Endo. Dr Yafi has disclosed no relevant financial relationships.

Sexual Medicine Society of North America (SMSNA) Fall 2017 Scientific Meeting. Abstracts 132 and 340. Presented October 26, 2017.

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