Research: Prostate Cancer Studies Explore New Treatment, Health Disparities

Research from Cedars-Sinai Cancer detailing the largest examination to date of prostate cancer in transgender women, as well as treatment options that improve outcomes in patients with recurrent prostate cancer, will be presented during the American Urological Association (AUA) annual meeting April 28-May 1 in Chicago.

Prostate cancer occurs in a gland near the bladder that produces seminal fluid and nourishes sperm. It often grows slowly, but can be aggressive and resistant to treatment.

“Despite advances in screening and treatment, prostate cancer remains one of the deadliest cancers,” said Stephen Freedland, MD, the Warschaw Robertson Law Families Chair in Prostate Cancer at Cedars-Sinai and associate director for Training and Education at Cedars-Sinai Cancer. “In these studies, we identify practice-changing new treatment options and shed light on a group of patients who are not on the radar for most clinicians.” 

Prostate Cancer in Transgender Women

Freedland is senior author of a research report detailing the first large case series of transgender women with prostate cancer, which is being presented at the meeting and simultaneously published in the peer-reviewed Journal of the American Medical Association (JAMA). The report suggests prostate cancer is far more common in these patients than previously thought.

“The entire medical literature on prostate cancer in transgender women, prior to this study, consisted of 10 case reports, leading some to believe it was rare. But this paper shows it isn’t as rare as those case reports suggest,” Freedland said. “Transgender women, no matter what gender-affirming surgeries they may or may not have had, have prostates and are at risk of prostate cancer.”

Freedland and co-investigators looked at data on prostate cancer patients in the Department of Veterans Affairs between 2000 and 2022 and identified 155 transgender women with prostate cancer. They noted that:

• The number of prostate cancer cases among transgender women was lower than expected, based on rates detected in cisgender male veterans.
• Only 8% of transgender women with prostate cancer were Black, while 29% of cisgender male veterans with prostate cancer were Black.
• Transgender women on estrogen—the most common feminization therapy—at the time of prostate cancer diagnosis had the most aggressive disease.

While the number of patients included was too small to allow for formal scientific conclusions, investigators theorize that lack of prostate cancer screening in transgender women—via a blood test for prostate specific antigen, or PSA—could be one of several factors that contribute to lower rates of prostate cancer diagnosis among these individuals.

“When a woman walks into a clinician’s office, the doctor doesn’t necessarily think of screening them for prostate cancer,” Freedland said. “But even among patients who have had gender-affirming surgery, we do not remove the prostate, which is a nuance that people don’t always think about.”

Freedland suggested lower rates of prostate cancer diagnosis among Black transgender women could be due to their reluctance to openly identify as transgender to their doctors, and thus doctors are not screening these patients. However, more study on this point is needed.

Lack of screening could also mean that prostate cancers in transgender women are detected at a later stage, when they are more likely to be deadly, Freedland said. But even transgender women who undergo PSA screening could have their prostate cancers missed if they are taking estrogen therapy, which causes PSA levels to drop.

“In cisgender men, we have traditionally considered PSA levels below 4 to be safe,” Freedland said, “but for patients on gender-affirming hormone therapy, PSA levels decrease dramatically and can even go down to zero. We don’t yet have data to determine where the cutoff value for PSA should be in transgender women, but we suspect that some of these cancers are currently being missed because the cutoff value being used is too high.

“We hope this report is eye-opening to people for whom this disease wasn’t even on the radar,” Freedland said. “The most important thing for transgender women and their healthcare providers to remember is that prostate cancer screening shouldn’t be neglected.”

Treatments Beyond the Standard of Care

Freedland is also senior author of research being presented at the AUA meeting that details new options for patients whose prostate cancer persists despite surgery and radiation therapy. The Phase III EMBARK clinical trial evaluated a drug that can boost effectiveness of the standard of care for recurrent prostate cancer—and works well on its own. 

Standard of care for recurrent prostate cancer is androgen deprivation therapy (ADT), using medication to drastically reduce levels of the male hormone testosterone, which fuels prostate cancer growth. Freedland and colleagues tested therapeutic options to address two common issues associated with ADT.

The first is that ADT does not completely eliminate testosterone, leaving some of the hormone circulating and able to stimulate tumor growth. The other issue associated with ADT is that it has challenging side-effects including loss of sexual function.

In this study of 1,068 prostate cancer patients from 244 sites in 17 countries, one-third received ADT alone (the standard of care), one-third received ADT plus enzalutamide—a medication that blocks the action of testosterone rather than lowering testosterone levels—and one-third received enzalutamide alone.   

Among patients receiving ADT plus enzalutamide, the risk of metastasis or death was reduced by 58% compared with ADT alone. And among patients receiving enzalutamide alone, risk was reduced 37% compared with ADT alone.

With both experimental options performing better than the standard of care, Freedland said some men might choose to add enzalutamide to their ADT treatment, while for others enzalutamide alone might be preferable.

“Some men might prefer enzalutamide alone as an option because it potentially allows them to avoid some of the side-effects associated with ADT, though further analysis of the trial data is needed to confirm that,” Freedland said. “The performance of enzalutamide, in combination with ADT and alone, is really impressive.”

The study was funded by Pfizer and Astellas Pharma, and the drug manufacturers are working toward securing Food and Drug Administration approval.

Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and the PHASE ONE Distinguished Chair, said that these two studies are examples of the breadth of prostate cancer research undertaken by Cedars-Sinai Cancer physician-scientists.

“Too many men in the U.S. still die from prostate cancer each year,” Theodorescu said. “Our investigators are dedicated to developing next-generation treatments to best care for each and every patient. They are committed to delving deep into the causes of prostate cancer detection and treatment disparities in underserved populations, such as the LGBTQ+ community that includes our transgender patients. Our goal is for all patients to receive the most effective, personalized care in the timeliest fashion.”

Learn more on the Cedars-Sinai Blog: Gender Affirming Cancer Screening