RE: Cancer Stage, Treatment, and Survival Among Transgender Patients in the United States

In “Cancer Stage, Treatment, and Survival Among Transgender Patients in the United States,” Jackson et al. (1) perform a retrospective analysis of patients diagnosed with cancer in the National Cancer Database between 2003 and 2016. In 2015, the American College of Surgeons updated their guidance on recording the “sex” variable so it will include “transsexual, natal male” and “transsexual, natal female” (2). The term “transsexual” will further be referred to as “transgender.” Although not specifically outlined by the American College of Surgeons, Jackson et al. (1) assume that “transgender, natal male” patients underwent gender affirmation surgery involving bilateral orchiectomy. The authors identified that transgender patients with prostate cancer were more likely to have worse overall survival (hazard ratio = 1.91, 95% confidence interval = 1.06 to 3.45) compared with patients who were cis-gender. Although a rare event, such cases can be devastating to patients and can be prevented by appropriate screening.

Prostate cancer screening has become increasingly complex, and there is no established guideline for prostate cancer screening for transgender patients (3,4). Prior studies involving transgender patients have been limited by small sample sizes and prior reviews have unsurprisingly determined there are limited data to further inform practitioners (2). One study suggested using a prostate-specific antigen (PSA) level of 1 ng/mL as the upper threshold of normal for transgender patients on antiandrogen therapy (5). However, this recommendation has not been validated and may not adequately reflect other causes for variations in PSA.

The use of novel biomarker tests in conjunction with PSA testing, digital rectal examination, family history, and possibly germline testing and multiparametric magnetic resonance imaging (MRI) could be useful adjuncts in this population (6). Biomarker tests such as SelectMDx and ExosomeDx tests have emerged as non–PSA-based urine tests. SelectMDx tests for mRNA levels of DLX1 and HOX6, and ExosomeDx tests for exosomal RNA levels of PCA3, ERG, and SPDEF. It is now believed that mutations in genes such as HOX6 and ERG contribute to androgen-independent prostate cancer (7). Although PSA levels can be affected by hormonal manipulation, the presence of these biomarkers in the urine of transgender patients may be useful in the determination of whether to pursue a prostate biopsy.

Furthermore, studies now support that between 6% and 16% of prostate cancer patients have an inherited predisposition. The most common germline mutations seen are those in the DNA repair pathway, and more specifically, the homologous recombination repair pathway, including BRCA1/2. Although such tests are not yet recommended in the screening population, emerging studies are investigating germline testing in patients who might be at risk for prostate cancer due to a family history of these mutations. Lastly, multiparametric MRI has redefined prostate cancer diagnosis and management. Its use as an additional study to determine whether to pursue biopsy is likely to be essential in guiding diagnosis. Ultimately, a comprehensive prostate cancer screening pathway for transgender patients involving PSA testing, family history, and digital rectal examination with consideration of novel biomarkers and possibly germline testing and MRI may play an important role in the future.

Funding

None.

Notes

Role of the funder: Not applicable.

Disclosures: The authors have no disclosures.

Author contributions: JJD: Writing—original draft; writing—review & editing. JTA: writing—review & editing. AS: writing—review & editing. CMJ: writing—review & editing.

Data Availability

No new data were generated or used for this correspondence.