AUA 2023: Treating Prostate Cancer In Transgender Women

With a growing transgender patient population, urologists and other healthcare providers involved in the treatment of genitourinary malignancies should expect to see more transgender women being diagnosed with prostate cancer. Data shows that in 2022, 1.3% of people between the ages of 18 and 24 in the United States identified as transgender, compared to 0.55% of the country’s older adults.[1]

At the annual meeting of the American Urological Association (AUA), held April 28 – May 1, 2023 in Chicago, Ill, at the McCormick Place, Chicago, IL , researchers from Cedars-Sinai Cancer presented results from a study investigating prostate cancer disease rates in transgender women and the implications the growing number of transgender women may have for public health. [2][3]

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,” noted 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 this 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).[2][3]

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 explained.

Study
Together with his co-investigators, Freedland looked at data on prostate cancer patients in the Department of Veterans Affairs between 2000 and 2022.  The data included data about the gender-affirming hormone therapies used, prostate-specific antigen (PSA), PSA density [lower risk, <0.15 ng/mL/g]), bilateral orchiectomy status, biopsy grade group (grades 1-5, with 5 being most severe), and clinical stage (T1-T4, with T4 being most advanced).[2]

They identified 155 transgender women with prostate cancer.  Of these transgender women with prostate cancer 116 never used estrogen, 17 formerly used estrogen, and 22 actively used estrogen at diagnosis.

The media age at time of diagnosis was 61 years with 88% of patients white with a median PSA was 6.8 ng/mL/. The median duration of estrogen use was 32 months among former and active estrogen users, 43% (50 of 115) were biopsy grade group 1, and 45% (49 of 108) were clinical stage T1.  Of the patients being diagnosed with prostate cancer, 98% (152 of 155) had not undergone bilateral orchiectomy. Biopsy grade group 1 or 2 was found in 58 of 82 patients (71%) with no prior estrogen use, 9 of 16 (56%) with former estrogen use, and 9 of 17 (53%) with estrogen use at diagnosis. [2]

Based on the outcome, the researchers noted that the number of prostate cancer cases among transgender women was lower than expected, based on rates detected in cisgender male veterans. The data also showed that about 8% of transgender women with prostate cancer were Black, while 29% of cisgender male veterans with prostate cancer were Black.

Freedland and his team further noted that transgender women on estrogen, which is 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.

Lack of screening: Barriers to care
The most observed barriers to care in the transgender female population are varied, but generally include accessing resources, medical knowledge deficits, ethics of transition-related medical care, diagnosing vs pathologising transgender patients, financial restrictions of the patient, and health system determinants.[4]

“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 added.

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 observed. 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.

Estrogen and PSA levels
“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,” Freedland added.

“Too many men in the U.S. still die from prostate cancer each year,” noted Dan Theodorescu, MD, PhD, director of Cedars-Sinai Cancer and the PHASE ONE Distinguished Chair.

“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,” Theodorescu concluded.

Reference
[1] Schmidt C. Prostate cancer in transgender women. What do we know about the risk? A new paper investigates. Online. Harvard Health Publishing/Harvard Medical School.
[2] Nik-Ahd F, De Hoedt A, Butler C, Anger JT, Carroll PR, Cooperberg MR, Freedland SJ. Prostate Cancer in Transgender Women in the Veterans Affairs Health System, 2000-2022. JAMA. 2023 Apr 29. doi: 10.1001/jama.2023.6028. Epub ahead of print. PMID: 37119522.
[3] Nik-Ahd F, De Hoedt A, Butler C, Anger JT, Carroll PR, Cooperberg MR, Freedland SJ PD20-04 Trends in Prostate Xancer Diagnosis in Trnasgender women: A national Study. Presented during the 2023 AUA meeting, Session: PD20: Equity & Inclusion: Health Equity & Outcomes III. https://doi.org/10.1097/JU.0000000000003286.04
PD20-04: Trends in Prostate Cancer Diagnosis in Transgender Women: A National Study[4] Deebel NA, Morin JP, Autorino R, Vince R, Grob B, Hampton LJ. Prostate Cancer in Transgender Women: Incidence, Etiopathogenesis, and Management Challenges. Urology. 2017 Dec;110:166-171. doi: 10.1016/j.urology.2017.08.032. Epub 2017 Sep 4. PMID: 28882782.