Top urologist/PCa patient: Could transdermal estradiol become an important hormone for treating advanced prostate cancer?

Some tips former AUA president to former U.S. President Joe Biden

(Editor’s note: Paul Schellhammer, MD, is one of the top urologists in the world. His CV is impressive:

—Professor, Urology/Eastern Virginia Medical School

—Chairman, Department of Urology/Eastern Virginia Medical School

—Director, Urology Training Program/Eastern Virginia Graduate School of Medicine

—Program Director, Virginia Prostate Center/Eastern Virginia Medical School/Sentara Cancer Institute

—President, American Urological Association (AUA)

—President, American Board of Urology

—President, Society of Urologic Oncology

He also is one of us—a prostate cancer patient. Paul has advanced PCa. He serves as a medical advisor to Active Surveillance Patients International.

I asked him what he thought about the treatment of former President Joe Biden, who is now undergoing radiation therapy.

He said, “No idea, and it must be confusing to the prostate cancer public as well. Would be so helpful to know who is calling the shots.”

Biden has been less than transparent about his treatment. That’s his right, of course, especially now that he’s out of the White House.

Paul noted about Biden: “Grade Group 5 metastatic disease with a 4–5 week course of radiation? Is it local plus bone/if local, why not deliver short-course SBRT and spare the multiple trips to radiation oncology?

“I’m also sure, as an 82-year-old like Biden would do better with transdermal estrogen for a better QOL [Quality of Life] experience. His experience could be a ‘teaching case’ instead of many why/what questions.”

Paul himself has used transdermal estrogen patches for years and points out some issues with their use in this essay. His essay may not have an immediate impact on most of us. But it will eventually help some of us who end up being treated.—Howard Wolinsky)

By Paul Schellhammer, MD

I thank Howard Wolinsky for giving me a chance to write for The Active Surveillor about transdermal estradiol (tE2) and its future role in prostate cancer (PCa) therapy. Active surveillance (AS) is a monitoring program for men diagnosed with low-risk PCa, with a low probability of progression that would threaten a PCa patient’s health and quality of life. However, the monitoring involved in a AS program by ~5 years typically identifies approximately 30-40 % of men whose disease is progressing, and they should thus proceed to treatment.

The common treatment options are radiation therapy (RT) or surgery. If radiation is chosen, there may be a discussion about the inclusion of androgen deprivation therapy (ADT) of variable duration (i.e., between 4 and 24 months) as part of the RT plan. This use of ADT as an adjunct to radiation is based on numerous large trials that demonstrate a survival benefit for combining ADT with RT. if you should be in the 30–40% progression group, below are some things to consider when discussing treatment options with your urologist and radiation oncologist.

The purpose ADT is to lower the male hormone testosterone to less than 20 ng/dl. Why?–Because testosterone stimulates PCa cancer cells to grow and multiply. The most common pharmaceutical agents used for ADT are termed LHRH agonists/antagonists. They can be delivered by injection or in pill form, and they are very effective in lowering testosterone to the targeted level. However, a little-appreciated effect of suppressing testosterone to this level is the virtual elimination of serum estrogen levels.

There are several estrogens, and all are commonly thought of as female hormones. But men normally also have estrogens in their bodies, of which the most common one is estradiol (E2). Men get their E2 from a simple chemical process that converts testosterone to estradiol.. This level estradiol is an essential contributor to overall male health. Most of the adverse events of ADT, which include hot flashes, sleep disturbance, weight gain, physical and mental fatigue (“brain fog”) and osteoporosis are secondary to this loss of E2. Although not as powerful as testosterone, E2 can even help preserve some sexual interest. Osteoporosis, which can lead to a high risk of fracture, is a critically important damaging effect of the absence of estrogens in men as it is in women after menopause.

Estrogens at high doses are themselves capable of lowering testosterone to castrate levels of less than 20 ng/dl. They can therefore achieve cancer control while at the same time reducing the adverse events of androgen suppression. Thus, using high-dose estrogen for ADT can improve the quality of life for the patient who needs androgen suppression to control their cancer

In a recently reported large trial in the United Kingdom, E2 was shown to be equivalent efficacy as the LHRH agents in controlling PCa. E2 is also much less costly than the LHRH agents.

Why then is E2 not discussed as a treatment option for ADT?

Approximately 75 years ago, a synthetic estrogen was the first drug therapy to lower testosterone–the other option was surgical castration. That estrogen back then was delivered as a pill. While effective in controlling PCa, it was associated with untoward cardiovascular side effects and was therefore abandoned.

We now know from the research out of the United Kingdom that the adverse effects of estrogens are associated with their oral ingestion. The cardiovascular risk can be eliminated by delivering the estrogen via the skin. Indeed, the E2 used in the recent UK study was administered via the transdermal route.

Because of the adverse cardiovascular events associated with oral estrogen therapy for PCa, the medical community may be reticent to discuss tE2 as an option for ADT despite its benefits in terms of both cancer control and quality of life compared to the LHRH drugs. I encourage PCa patients, who are exploring treatments for PCa after AS, to explore the option with their urologist and oncologist.

There is though, another barrier to using tE2 for ADT. The products currently available for the transdermal delivery of E2 are FDA-approved only for use in women. Efforts are now underway to have an estrogen delivery system approved for men seeking better options for ADT.

If you would like to know more about efforts to make tE2 products an approved option of ADT for men, view the Estradiol Initiative website.

Physicians may express reluctance to prescribe tE2 for ADT. Still, I invite you to initiate a shared decision-making discussion if RT with ADT is recommended for the treatment of your cancer.

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Ripped from the headlines: Are Bi-Parametric MRIs Ready for Prime Time?

By Howard Wolinsky

Ripped from the headlines: You can get a quick MRI and avoid gadolinium contrast and maybe avoid claustrophobia.

You can also learn more about this at an ASPI webinar, featuring researchers who have demonstrated that images from biparametric, non-contrast MRIs are as useful as those from traditional multiparametric MRIs with gadolinium contrast. Many patients have been concerned about potential brain issues because GAD crosses the blood-brain barrier,

This expert panel, comprising researchers from University College London and the University of Michigan, will examine the latest evidence on bi-parametric MRI and whether it is ready to replace multiparametric MRI in everyday clinical practice.

When: The session will run from 12:00 to 1:30 p.m. Eastern Time, Saturday, October 25.

Register here

https://zoom.us/meeting/register/zaRxI7dbTTq5lnlAd6ASAA

This webinar could change your life—or at least how your low-risk prostate cancer is monitored.

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Calling all AS spouses

There are support groups for spouses of prostate cancer patients. They tend to be targeted at women whose husbands have advanced prostate cancer. A small group of partners has been discussing starting what may be the first support group aimed at spouses of patients on Active Surveillance. If you’re interested, email me at howard.wolinsky@gmail.com