PROSTATE CANCER Prostate Cancer in Transgender Women: Raising Awareness in Our Most Marginalized Populations
By: Farnoosh Nik-Ahd, MD, University of California, San Francisco; Jennifer T. Anger, MD, MPH, University of California, San Diego; Christi Butler, MD, University of California, San Francisco; Maurice M. Garcia, MD, MAS, Cedars-Sinai Medical Center, Los Angeles, California; Peter R. Carroll, MD, MPH, University of California, San Francisco; Matthew R. Cooperberg, MD, MPH*, University of California, San Francisco; Stephen J. Freedland, MD*, Cedars-Sinai Medical Center, Los Angeles, California (*Co-senior authors) | Posted on: 19 Sep 2023
Though prostate cancer has historically been thought of as a cancer affecting men, there are recent efforts to increase awareness of prostate cancer in transgender women (women with male assigned sex at birth).1,2 In light of ongoing marginalization and discrimination affecting transgender and gender-diverse individuals, we commend the AUA’s recent position statement on the commitment to caring for transgender and gender-diverse individuals.3 Urologists play a key role not only in the gender-affirmation process, but also in leading our understanding of prostate cancer in transgender women and in raising awareness of this important subject among patients and providers.
Though transgender women may undergo gender-affirming genital surgery via varying approaches, these women retain their prostates regardless of the surgery performed. As such, they remain at risk of prostate cancer and should still be considered for prostate cancer screening and undergo assessment of risk factors (similar to cisgender men), including family history and racial background. Historically, prostate cancer in transgender women was thought to be very rare with literature on this limited to only 10 case reports.4 Recently, however, we published the largest case series on this subject to date, which consisted of 155 transgender women within the Veterans Health Administration who were diagnosed with prostate cancer.5 We initially identified a cohort of 449 people with ICD (International Classification of Diseases) codes for both transgender identity and prostate cancer. After chart review to confirm transgender identity and prostate cancer diagnosis details, we identified 155 subjects. Patients were stratified by estrogen usage given it is the most common gender-affirming hormone and typically results in a castrate environment, and thus may impact prostate cancer diagnosis and aggressiveness. Specifically, we hypothesized that women on estrogen at the time of prostate cancer diagnosis may have worse disease (ie, the disease was already partially castrate resistant). Among this cohort, 116 had never used estrogen, 17 were formerly on estrogen (stopped prior to prostate cancer diagnosis), and 22 were actively on estrogen at diagnosis. Only 8% of transgender women with prostate cancer were of Black race compared to 29% of cisgender male veterans.6 The implications of these findings are that prostate cancer in transgender women is not as rare as suggested based on previous case reports. However, rates were ∼60% lower than expected based on estimates in cisgender male veterans. Interestingly, patients actively on estrogen at diagnosis had the highest PSA density and highest proportion of Grade Group 5 disease, both markers of prostate cancer aggressiveness. Thus, consistent with our hypothesis, transgender women on gender-affirming hormones may have more aggressive disease or potentially delayed diagnosis. Delayed diagnosis may be due to lack of awareness of the need to screen as well as patient avoidance of health care settings due to misgendering and mistreatment.7
It remains to be elucidated whether prostate cancer in transgender women is indeed less common or underdiagnosed relative to cisgender men. Specifically, several factors may contribute to possible underdiagnosis or delayed diagnosis that urologists, specifically, should be aware of. These include a lack of awareness that these women have prostates and thus are at risk of prostate cancer, lower PSA screening rates in transgender women, the suppressive effects of estrogen on prostate cancer development, or false reassurance from “normal” PSA values. Historic PSA reference ranges are based on cisgender male data, whereas transgender women on gender-affirming hormones would be expected to have significantly lower PSAs due to estrogen causing castrate testosterone levels. Thus, the historic reference ranges are likely inappropriate for transgender women on gender-affirming hormones, and a normal PSA value in a transgender woman on estrogen may indeed warrant further evaluation.
Key areas of future research include establishing new PSA reference ranges for transgender women that specifically factor in the effects of gender-affirmation hormones. Additionally, transgender women are notably absent from PSA screening guidelines from all leading organizations. Though transgender women not on gender-affirming hormones should undergo PSA screening as per cisgender guidelines, future work should aim to create guidelines on how best to screen transgender women on gender-affirming hormones, including both the timing of PSA screening relative to gender-affirming hormone therapy initiation and the optimal screening interval. Though not yet evidence based, we suggest screening transgender women on gender-affirming hormones at regular intervals and using a PSA cutoff of >1 ng/mL at any age, consistent with prior work,8 as cause for further assessment and/or careful surveillance. Note that further assessment does not necessarily mean immediate biopsy, but rather evaluation with possible repeat PSA tests and/or MRI. As the impact of estrogen and subsequent castration on other prostate cancer biomarkers remains unknown, secondary biomarkers should be used cautiously until more data are generated. Additionally, we encourage clinicians to be wary of a rising PSA in transgender women on gender-affirming hormones.1 For patients on finasteride, a weak form of hormonal therapy, the Food and Drug Administration suggests further investigation of a rising PSA, even if still within “normal” reference ranges.9 Similarly, we encourage clinicians to consider careful assessment of a rising PSA in transgender women on gender-affirming hormones, which are generally far more potent forms of hormonal therapy than 5α-reductase inhibitors. Like patients with a PSA >1 ng/mL, further assessment may include repeat PSA and/or prostate MRI to further risk stratify patients, with other biomarkers being used cautiously.
Finally, understanding the patient experience can be a powerful means of creating change, particularly in terms of decreasing the stigma and marginalization that may come with discussing a “man’s” cancer with transgender women. We encourage urologists to engage in patient-centered discussions on PSA screening with transgender women, understand the patient perspective, and serve as an ally to help understand potential barriers to screening and decrease delayed health-seeking behaviors. Clinicians should also be aware of additional barriers at the intersection of race, socioeconomic status, or access to care that may disproportionately affect transgender patients. As the number of individuals openly identifying as transgender continues to increase, urologists play a key role in our understanding of prostate cancer in this population and how to provide comprehensive, patient-centered care in a nuanced and thoughtful manner.
- Nik-Ahd F, Anger JT, Cooperberg MR, Freedland SJ. Prostate cancer is not just a man’s concern—the use of PSA screening in transgender women. Nat Rev Urol. 2023;20(6):323-324.
- Nik-Ahd F, Jarjour A, Figueiredo J, et al. Prostate-specific antigen screening in transgender patients. Eur Urol. 2023;83(1):48-54.
- American Urological Association. Transgender Care: Position Statement. 2023. https://www.auanet.org/about-us/policy-and-position-statements/transgender-care
- Deebel NA, Morin JP, Autorino R, Vince R, Grob B, Hampton LJ. Prostate cancer in transgender women: incidence, etiopathogenesis, and management challenges. Urology. 2017;110:166-171.
- Nik-Ahd F, De Hoedt AM, Butler C, et al. Prostate cancer in transgender women in the Veterans Affairs health system, 2000-2022. JAMA. 2023;329(21):1877.
- Makarov DV, Ciprut S, Walter D, et al. Association between guideline-discordant prostate cancer imaging rates and health care service among veterans and Medicare recipients. JAMA Netw Open. 2018;1(4):e181172.
- Seelman KL, Colón-Diaz MJP, LeCroix RH, Xavier-Brier M, Kattari L. Transgender noninclusive healthcare and delaying care because of fear: connections to general health and mental health among transgender adults. Transgend Health. 2017;2(1):17-28.
- Gooren L, Morgentaler A. Prostate cancer incidence in orchidectomised male-to-female transsexual persons treated with oestrogens. Andrologia. 2014;46(10):1156-1160.
- U.S. Food and Drug Administration. Full Prescribing Information: Finasteride. Accessed July 10, 2023. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/020788s028lbl.pdf