Expert Highlights ‘Paradigm Shift’ Surrounding Testosterone Therapy for Metastatic Prostate Cancer

Mohit Khera, MD, MBA, MPH, Scott Department of Urology at Baylor College of Medicine

A paradigm shift has taken place over the past 2 decades with regard to perceptions around testosterone therapy as a treatment for metastatic prostate cancer, potentially opening the door for a novel strategy for the population, according to Mohit Khera, MD, MBA, MPH; however, he emphasized that confirmatory phase 3 research is necessary to push the needle forward for the treatment.

During the 2022 Society for Urologic Oncology (SUO) Annual Meeting, CancerNetwork^® spoke with Khera, a professor in the Scott Department of Urology at Baylor College of Medicine, about the potential benefit of high-dose testosterone therapy in select patients with prostate cancer.

In particular, he emphasized the potential promise of bipolar androgen therapy in which patients with prostate cancer have achieved benefit from high doses of testosterone. However, he noted the important of conducting further research into this strategy.

“It’s also important to foster these studies using bipolar androgen therapy in treating men with metastatic prostate cancer,” Khera said. “It's a completely novel way of treating metastatic prostate cancer. More research needs to be done.”

CancerNetwork^®: How has the perception surrounding testosterone therapy for metastatic prostate cancer changed over time?

Khera: Over the past 20 years, there's been a paradigm shift in our understanding of how testosterone therapy affects the prostate. When I was a resident 20 years ago, I was taught that testosterone was dangerous to give to men because it would increase the risk of them developing prostate cancer. When I finished my residency 6 to 7 years later, we started thinking that maybe it is safe. Now, there's a paradigm shift to think that testosterone therapy may be protective or therapeutic in the treatment of prostate cancer.

What data have we seen in support of testosterone therapy in this population?

There are some data to suggest that those patients with lower testosterone levels are more likely to progress on active surveillance. Many of us, including myself, are checking testosterone levels in men who are on active surveillance. We have also seen new modalities and treatments in terms of bipolar androgen therapy where we give men high doses of testosterone as treatment for metastatic prostate cancer. Ten years ago, that would have been unheard of to give high doses of testosterone to men with metastatic prostate cancer. But today, we're seeing improvements in patients with metastatic disease.

Where does research need to be focused to push the needle forward for testosterone therapy in prostate cancer?

It's important to realize that we've not had any randomized placebo-controlled trials assessing the use of testosterone therapy in metastatic prostate cancer; that's important. That's something that we need to consider doing in the future. But it's also important to foster these studies using bipolar androgen therapy in treating men with metastatic prostate cancer. It's a completely novel way of treating [this disease] and more research needs to be done.

What do you hope your colleagues from the community setting take away from your research?

Some urologists still believe that testosterone may increase the risk of prostate cancer. Many urologists are also uncomfortable giving testosterone because of this risk. They need to understand that the paradigm has shifted. In 2018, the American Urological Association put out testosterone guidelines stating clinicians should inform patients of the absence of evidence linking testosterone therapy to the development of prostate cancer.

Now, in those same guidelines, they do state that patients with testosterone deficiency and a history of prostate cancer should be informed that there is inadequate evidence to quantify the risk-benefit ratio of testosterone therapy. Further research needs to be done for testosterone [therapy] in men who have a history of prostate cancer.

Reference

Mulhall JP, Trost LW, Brannigan RE, et al. Evaluation and management of testosterone deficiency: AUA guideline. J Urology. Published online August 1, 2018. doi:10.1016/j.juro.2018.03.115