The prostate gland is not removed during gender-affirmation surgery in transgender women. Hence, they are at risk of prostate cancer. A case series published in JAMA evaluated the prevalence of prostate cancer among transgender women and found that it was far more prevalent than thought to be.¹ Around 14 cases were detected per year among transgender women.

In this study, researchers from the United States reviewed records of Veterans Affairs on prostate cancer between 2000 and 2022. Data was also reviewed to establish transgender identity and diagnosis of prostate cancer. The data examined included to 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; 5 being most severe) and clinical stage (T1-T4; T4 considered as the most advanced).

A total of 155 transgender women with prostate cancer were identified. Of these, 116 had never used estrogen as feminization therapy, 17 had used estrogen earlier but stopped prior to diagnosis, while 22 were active estrogen users at the time of diagnosis of prostate cancer. At the time of diagnosis, the median age of the patients was 61 years and the median PSA level was 6.8 ng/mL.

Among the former and active users of estrogen, the median duration of estrogen use was 32 months. 43% were biopsy grade group 1 and 45% were clinical stage T1. Bilateral orchiectomy had not been performed in the majority of the patients (98%; 152/155) with prostate cancer.

Seventy-one percent (58/82) of patients without estrogen use, 56% (9/16) of former estrogen users and 53% (9/17) who were active estrogen users at diagnosis had biopsy grade group 1 or 2.

Biopsy grade group 4 or 5 was found in 23% (19/82) of patients who had never used estrogen; of these 12% were biopsy grade group 5. 25% (4/16) of former users had biopsy grade group 4 or 5 cancer with 6% having grade group 5. Among the active users, 35% (6/17) had biopsy grade group 4 or 5 cancer; of which, 29% were in grade group 5.

The median PSA density was 0.21 ng/mL/g in never estrogen users, 0.26 ng/mL/g among former users, while in active users, the median PSA density was 0.31 ng/mL/g.

These observations show that the occurrence of prostate cancer in transgender women is not as rare as believed to be based on the current evidence although the rates were lower than those in cisgender male veterans. However, the lower rates can be attributed to inadequate screening for prostate cancer owing to lack of awareness among both patients and doctors or associated stigma because of which the transgender women may not be open to identifying themselves as transgender. Also, raised PSA levels may be undetected due to falsely normal results or levels that are much below the cut-off of 4 among cis-gender men, due to use of gender-affirming hormone therapy leading to missed diagnosis. Delayed diagnosis means delayed treatment.

In the present study, transgender women on estrogen at diagnosis had the highest PSA density and the percentage of patients with biopsy grade group 5 prostate cancer was also highest among the active users suggesting that this group had the most aggressive disease.

Hence, they should be screened for prostate cancer. Surveillance strategies to optimize detection of prostate cancer in transgender women such as using a lower PSA cut-off level are needed for early initiation of treatment and better patient outcomes.

Reference

1. Farnoosh Nik-Ahd, et al. Prostate cancer in transgender women in the Veterans Affairs Health System, 2000-2022. JAMA. 2023 Apr 29;e236028. doi: 10.1001/jama.2023.6028.