This transcript has been edited for clarity. For more episodes, download the Medscape app or subscribe to the podcast on Apple Podcasts, Spotify, or your preferred podcast provider.
Sandhya Srinivas, MD: Hello. I'm Sandy Srinivas, host of the Medscape InDiscussion podcast series on prostate cancer. Today I'm really excited that we will discuss treating prostate cancer in transgender patients. I hope that we'll be able to highlight the barriers to diagnosis and treatment and the importance of providing gender-affirming care. It is my pleasure to introduce my guest, Dr Aria Olumi, who is an accomplished clinician educator and investigator, is a Janet and William DeWolf Professor of Surgery and Urology at Harvard Medical School, and is the chief of urology in the Department of Surgery at Beth Israel Deaconess Medical Center. Dr Olumi is internationally recognized for his multifaceted work in the field of urology and directs a lab funded by the National Institutes of Health (NIH). Welcome to the Medscape InDiscussion podcast, Dr Olumi.
Aria F. Olumi, MD: Thank you for having me. I am looking forward to this conversation.
Srinivas: Tell us what led you to urology, specifically the field of studying transgender patients.
Olumi: I became interested in urology in medical school because of mentors that I was involved with. I initially started working on bladder cancer research in a laboratory in medical school, looking at genetic modifications in low-grade and high-grade bladder cancer. In addition to my basic science mentor, I was also coupled with an outstanding clinical surgeon at University of Southern California. The combination of those two mentors was a result of me pursuing urology as a career.
Srinivas: How did you get into the field of taking care of transgender patients?
Olumi: Oftentimes in clinical medicine, we learn from our patients as far as the needs and areas where we should focus our attention. In our multidisciplinary genitourinary oncology clinic, we had the opportunity to meet a patient who had been seen for a third opinion for management of newly diagnosed prostate cancer. This was back in 2018. As a result of this woman presenting to our clinic — a new entity for me — the more research I did on the topic, the more I learned that there's a huge, unmet need and a gap in our knowledge, both as clinicians and healthcare providers, at all levels — from physicians to advanced practice providers, to nurses, to our office administrative staff — about how to really communicate with this patient population. That's how I became interested in learning more and providing appropriate care for our patients.
Srinivas: Well, it's really a pleasure to have you, and I'm looking forward to all of us learning from your experience and expertise in this topic. Maybe we can start off by you telling us how many transgender patients exist and what we know about the incidence of prostate cancer in transgender women.
Olumi: Let's perhaps start off by defining who is a transgender individual. "Transgender" is an umbrella term for people whose gender identity and/or expression is different from the cultural expectations based on the sex that they were assigned to at birth. I think understanding that definition is critically important for us as healthcare providers to identify and communicate with our patients in an appropriate manner. The number of transgender patients in the United States has been growing over the past decade. At last count, we have 1.4 million individuals in the United States who identify as transgender, about half a percent of the US adult population. But that number has doubled since its last count in 2011. Globally, it is estimated that about 1.2% of the population identify as transgender individuals.
Srinivas: Who is the team that is providing care for these patients? I would imagine that there must be a team of providers that they encounter. Talk a little bit about your experience. Who have you seen provide care for this group of patients?
Olumi: At our medical center, Beth Israel Deaconess Medical Center, we have a multidisciplinary clinic that is led by endocrinologists, urologists, plastic surgeons, obstetricians/gynecologists, and mental health specialists and social services personnel who care for transgender patients. A patient's need may vary depending on whether, for example, they just need general medical care or hormonal care or surgical care. The surgical care can be anywhere from facial surgery to breast surgery or genitourinary-related aspects of surgery. Depending on that, different surgical members of the team would obviously be involved in caring for those patients. It requires a multidisciplinary team and requires an institution that is sensitive to the needs of transgender patients.
Srinivas: Talk a little bit about the journey that the patient goes through. There is gender-affirming hormonal therapy, and then there is gender-affirming surgery. My understanding of gender-affirming hormonal therapy really involves patients having their androgens, their testosterone, suppressed. That's usually done by anti-androgens with either spironolactone or cyproterone acetate. Most of these women are on lifelong estrogen. Maybe you can tell us a little bit about the gender-affirming surgery that these patients go through.
Olumi: Typically for gender-affirming hormonal treatments, patients have been on hormonal management for many years. Usually it's a dual therapy. It's either androgen secretion suppression or a gonadotropin-releasing hormone (GnRH) agonist, or by suppression using spironolactone, as you mentioned, in combination with some kind of estrogen, estradiol replacement therapy. Estradiol replacement therapy is a cornerstone, plus one of the other treatment modalities, whether it is a GnRH agonist or spironolactone; in some cases, 5-alpha-reductase inhibitors may also be used. The gender-affirming surgery part of it can be quite involved and complex, and it can involve plastic surgeons for facial surgery; ear, nose, and throat specialists for vocal chord surgery manipulations; plastic surgeons for breast surgeries; and urologists or plastic surgeons in combination who may do different forms of gender-affirming, perineal, or genitourinary-related surgeries. Typically, individuals undergo orchiectomy, or removal of the testicles, and removal of the phallus, followed by creation of a neovagina. There are many different forms of creating the neovagina. I personally am not a reconstructive urologist. My area of expertise is urologic oncology, but we do have a specialist on our staff who is a gender-affirming surgeon; she's an expert in this area. It is an involved surgery. It does require experts in a multidisciplinary team to work collaboratively for best results and outcomes.
Srinivas: I think both you and I are at an institution where we have the luxury of having this multidisciplinary team. Outside of this type of high academic program, how do you foresee patients having access to this level of multidisciplinary team care, and can you discuss the competency and the education needed for providers to help care for these patients?
Olumi: It's challenging. This type of care, whether it's nonsurgical or surgical, is not often taught in medical school or a residency training program. It's only recently that this type of care is gaining more acceptance — even talking about caring for this population of patients, who have been marginalized for many, many years. In rural areas, I think it would be quite challenging for patients to have expert level of care for these types of complex, management strategies, particularly the technical aspect of the reconstructive surgery. Perhaps the hormonal therapy part of it could be managed by telehealth, or remotely, a little more easily than the technical surgical aspect of it, which really requires a team that works well together. Unfortunately, at this point in time, this is focused on certain areas of the country, at certain centers, which have been forward-thinking in providing this level of care for our patients.
Srinivas: It certainly sounds very complicated, and I'm really hopeful that episodes like this will help improve awareness and help meet the unmet needs for this group of patients. I wanted to switch gears to the topic for why we are here, which is how do we diagnose prostate cancer? Transgender women have a prostate in place. Removal of a prostate is not part of the surgery. How do we do prostate cancer screening for these patients? Screening is controversial, even in cisgender patients, but over the past many decades, we have had societies and guidelines give us some direction about what is the prostate-specific antigen (PSA) cutoff. What is the age at which PSA screening should start? What do we know about PSA screening in transgender women?
Olumi: I think it's important to identify the different levels of transgender patients. If an individual identified as a transgender individual, and they have been taking hormonal replacement therapy, multiple clinical studies have shown the risk for prostate cancer in that individual to be decreased. It's also important to identify that for individuals who may identify as transgender but are not taking hormonal replacement treatments, their risk for prostate cancer is equal to that of their cisgender counterparts. For individuals who have been on lifelong estrogen replacement hormonal therapies, the two aspects that we discussed earlier, with the GnRH agonist and estrogen replacement, studies have suggested that there may be about a fivefold decrease in rate of prostate cancer in transgender women. In some studies, it is suggested that approximately 4 out of every 10,000 individuals may be at risk of developing prostate cancer. The younger the individual starts the hormonal therapy, the more protective the hormonal therapy is for reducing that risk. The later in life that the hormonal therapy medications are induced, the risk for prostate cancer is closer to that of cisgender counterparts. Overall, in the biggest study that was done in the Netherlands, the risk for prostate cancer is about fivefold lower in individuals who have been on lifelong estrogen replacement therapy.
Srinivas: Once they do have the diagnosis, it could be a little more aggressive, given that they've been on hormonal therapy, correct?
Olumi: Yes, absolutely. That's absolutely true. Because of the suppression of the hormones that are involved in prostatic growth and prostate cancer risk, when prostate cancer presents in patients who have been on lifelong hormonal replacement therapy, those cancers tend to be more aggressive — at a higher grade, at a higher stage, and in a more advanced stage, called castration-resistant prostate cancer. These are more advanced stages of the disease and require more aggressive forms of therapy.
Srinivas: Given that these patients are on hormonal therapy, clearly that's going to have an impact on their PSA. The starting PSA is going to be low in many of these patients. In cisgender patients, we have a cutoff; even their PSA is age dependent. While we have thought about this magic number of 4, even that's altered in cisgender patients. Is there a PSA cutoff that we should be informing our primary care providers and other team members about who are caring for transgender patients — to have a PSA cutoff in mind that should then trigger a workup?
Olumi: Yes. A PSA cutoff of about 1 ng/mL is suggested for patients who are transgender and have been on prolonged periods of estrogen replacement therapy as transgender women. Those are just recommendations and suggestions, but I think using a PSA cutoff of 1 or greater, which may lead to additional screening tools, is a reasonable number to aim for.
Srinivas: Multiparametric MRI has become a standard tool that we use for all patients with prostate cancer. I presume that would be a good tool in these patients as well. I'm really curious about the other tests, such as digital rectal exam (DRE), which could be a challenge, and then maybe we can learn a little bit from you about the challenges associated with a biopsy to prove the diagnosis in these patients.
Olumi: Before we get to that, maybe you'll allow me to also touch upon the age of initiating screening and diagnosis as it relates to the 1 ng/mL cutoff value. For individuals who may not have a familial risk for prostate cancer, the recommended timing for initiation of screening is at about age 50. For those who may be of African American descent or may have a familial history of prostate cancer with a first-degree relative being diagnosed with prostate cancer, the recommendation is to start screening at around age 45. For those who may have a hereditary genetic risk associated with increased risk for prostate cancer, like BRCA1 or BRCA2 genes, the recommended age for initiation of screening is 40. I just wanted to mention that. We talked about multiparametric MRI, which is an important tool to utilize for assessment of the prostate, for any suspicious lesions that need to be targeted and biopsied. I think the challenges of performing the prostate biopsy in transgender women have been overcome. In many individuals who've had neovaginal surgery, their biopsies can be done through the neovagina or through transperineal prostate biopsies, which can also be done with the transneovaginal probe for the ultrasound imaging and then the transperineal approach for the biopsies to be obtained. Those are two approaches that can be used for the biopsies.
Srinivas: Once we make a diagnosis of prostate cancer, we use the same tools that we use in cisgender patients to stage them, such as either a CT, a bone scan, and now, more recently, PSMA-based PET imaging — that's something that should be offered to all of these patients. Assuming that somebody has localized disease, what's the next approach from a urologic perspective?
Olumi: From a urologic perspective, the options for treatment are either surgery or nonsurgical approaches. If it's felt that the cancer is too far advanced, then the approach is for systemic therapies. For localized cancer treatment management, the challenge from a surgical standpoint is that the surgical planes between the prostate, neovagina, and rectum have obviously been modified. If an individual is going to have surgery, there are significant surgical technique challenges that need to be taken into consideration so that the neovagina is not damaged for prostate cancer treatment. Similarly for nonsurgical approaches with radiation or radiotherapy, the effect of radiation to the colon and rectum is well recognized. However, less is known about how that radiation may affect the neovagina. I think the risk for neovaginal stenosis, bleeding and so forth, is less understood in this patient population. So again, we see the importance of being treated at a center that has a multidisciplinary approach and experience with managing transgender patients with this diagnosis.
Srinivas: I'm a genitourinary medical oncologist, and in this podcast series, we have discussed survivorship issues for patients who are on long-term androgen deprivation therapy, including bone health, where we focus on their risk for osteoporosis and on cardiovascular health — having a need to monitor lipids and hypertension. For this group of patients, it really feels that mental health is such a big part, given their past journey coming into this, and I think it reiterates your statement about the need for a multidisciplinary approach. In the last few minutes that we have, can you talk a little bit about what your message would be for providers to improve the quality of healthcare, from screening through treatment?
Olumi: I think the one important thing is for all individuals in the healthcare industry — from physicians to nursing staff to advanced practice providers, to medical assistants, to our office administrative staff — is to recognize that the number of transgender females is increasing globally, and more and more individuals are going to require our services and our compassionate care to appropriately care for them. Educating our healthcare providers so that they can be sensitive and appropriately communicate and manage this population of patients is of utmost importance. Also important is avoiding marginalization of the patient so that our patients follow up with us to get the appropriate care that they need and have the best outcomes possible. I think that that's a very, very important aspect. That's one thing that we have done at our institution; we have started educating our administrative office staff who answer the phone, who greet the patients when they check in. That goes a long way in providing a welcoming environment for our patients, particularly for transgender patients. I think having longitudinal registries is very important. Also important is being more inclusive in our language for clinical trials. Typically in prostate cancer clinical trials, inclusion criteria are listed as being a male individual; transgender females are excluded from these clinical trials. However, I strongly feel that this population of patients who present with prostate cancer provide a very unique opportunity for us to study the biology of the disease and potentially come up with new treatment strategies, because this is really the first population of patients that we would ever see who present with hormone-insensitive prostate cancer or castration-resistant prostate cancer, and newer therapies and newer approaches may need to be devised for caring for this population of patients. It also allows us to study the biology of the disease where we do not have that opportunity in cisgender patients.
Srinivas: What additional resources are you aware of, Dr Olumi, that would be helpful for patients as well as for providers caring for these transgender patients?
Olumi: Both for patients and providers, the World Professional Association for Transgender Health (WPATH) is a very well-organized society multidisciplinary group of physicians and healthcare providers who study and come up with strategies for providing the best possible care for transgender patients. They have resources available for patient education and physician education. Many excellent resources can be accessed through the WPATH website.
Srinivas: Thank you so much, Dr Olumi. I learned an incredible amount from our conversation, and this is going to be really helpful for our listeners as well. Thank you, all, for tuning in. Please take a moment to download the Medscape app to listen and subscribe to this podcast series on prostate cancer. This is Sandy Srinivas for the Medscape InDiscussion podcast.
Resources
Prostate Cancer in Transgender Women: What Does a Urologist Need to Know?
How Many Adults and Youth Identify as Transgender in the United States?
Gender-Affirming Hormone Therapy: An Updated Literature Review With an Eye on the Future
Prostate-Specific Antigen Testing
Prostate-specific Antigen Screening in Transgender Patients
Multiparametric MRI for the Evaluation of Prostate Cancer
BRCA2 Gene Mutation and Prostate Cancer Risk. Comprehensive Review and Update
PSMA PET-CT in the Diagnosis and Staging of Prostate Cancer
World Professional Association for Transgender Health (WPATH)
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Cite this: Prostate Cancer and Transgender Patients: Providing Gender-Affirming Care During Screening, Diagnosis, and Treatment - Medscape - Nov 21, 2023.
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