The Shocking Truth About Women and Bladder Cancer

 

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Dr. Armine Smith

 
In this episode of Bladder Cancer Matters, host Rick Bangs speaks with Dr. Armine Smith, Director of Urologic Oncology at Sibley Memorial Hospital and a leading expert in bladder cancer. They dive deep into the significant disparities in bladder cancer diagnosis and outcomes between men and women, exploring the biological, socioeconomic, and healthcare-related factors behind these differences.

Dr. Smith highlights the urgent need for better awareness, timely diagnosis, and gender-sensitive treatment options, including exciting new research into the role of the microbiome and sex hormones in bladder cancer progression. With her passion and expertise, Dr. Smith offers actionable insights for both patients and healthcare providers. Tune in to learn about these critical issues and how we can collectively work to improve bladder cancer care for women.

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Transcript

Voice over:

This is Bladder Cancer Matters. The podcast for bladder cancer patients, caregivers, advocates, and medical and research professionals. It’s brought to you by The Bladder Cancer Advocacy Network, otherwise known as BCAN. BCAN works to increase public awareness about bladder cancer, advances bladder cancer research, and provides educational and support services for bladder cancer patients and their loved ones. To learn more, please visit bcan.org.

Rick Bangs:

Hi. I’m Rick Bangs, the host of Bladder Cancer Matters. A podcast for, by and about the bladder cancer community. I’m also a survivor of muscle invasive bladder cancer, a proud owner of a 2006 model year neobladder, and a patient advocate supporting cancer research at the Bladder Cancer Advocacy Network, or as many call it, BCAN. Producers of this podcast. I’m pleased to welcome Dr. Armine Smith. Dr. Smith is the director of Urologic Oncology at Sibley Memorial Hospital, an assistant professor of urology at Johns Hopkins University and adjunct faculty at George Washington University. She’s also co-director of the Bladder Cancer Program For Women at Sibley Memorial Hospital, which is also part of the Greenberg Bladder Cancer Institute at Johns Hopkins Medicine. Dr. Smith has expertise in urologic oncology, with special interest in bladder cancer, complex urological reconstruction and organ sparing surgeries. She has been a recipient of multiple awards, including the Cleveland Clinic Innovator Award in 2006, and the Cleveland Clinic House Staff Association Award in 2010. In addition to a BCAN John Quale Fellowship Travel Award in 2012, A Women’s Achiever Award in 2023, Outstanding Clinical Instruction Award in 2023 as well.

Physician of the year in 2024, and recognition as a top doctor in D.C and Virginia from multiple years in a row. Dr. Smith has also contributed to various research, publications and presentations. Welcome, Dr. Smith.

Dr. Armine Smith:

Thank you, Rick. It is a pleasure to be here on Bladder Cancer Matters.

Rick Bangs:

It’s our pleasure to have you. So, I wanted to start with some statistics. So in the US, in 2023, just one year ago, 63,000 men and 20,000 women were diagnosed with bladder cancer. And this aligns with what we know to be the historical rates that favor, if we can call it favor, men, three to one in terms of bladder cancer incidents. And women tend to be diagnosed later and have poorer outcomes, particularly African-American women. So can you tell us what’s behind these disparities?

Dr. Armine Smith:

Well, these disparities are rooted in several factors. There are differences in anatomy and biological processes in women, as you correctly point out. While men are diagnosed more frequently, women unfortunately tend to be diagnosed at more advanced stages. Part of this delay is due to the way women present with these symptoms, which are often mistaken for other conditions such as urinary tract infections and you know, GYN type of bleeding. Another layer is racial disparity, particularly for African-American women, who face even worse outcomes. Access to healthcare, socioeconomic factors, potential biases in medical treatment, all contribute to these disparities. It’s not just the US problem. Globally we see similar patterns, but the extent of the differences varies depending on the local healthcare systems, countries, some societal factors as well.

Rick Bangs:

But if we went outside the US, we would see very similar statistics in terms of incidence, in terms of being diagnosed later as a woman and having poor outcomes.

Dr. Armine Smith:

That is correct. This is not unique to the US. There are some minor differences in countries, incidences and mortality. Although the statistics differ a little bit, and healthcare systems are different, many countries report similar gender-based disparities. The implications are significant, because it suggests that we need a worldwide effort to improve early detection and treatment success for women. So collaborating on research, sharing best practices internationally could help address these issues on a broader scale.

Rick Bangs:

Okay. So I want to talk about the causal factors here. So we talked a little bit about anatomy, so let’s probe a little bit on that. So as a male, my urethra is going to be longer. Does that contribute? Is it hormonal? Why would men have more incidence? Do I smoke more often?

Dr. Armine Smith:

Well, great question. And I think you’ve touched on some of these a little bit with the way you were leading me to answer this question. So when we talk about disparities in bladder cancer outcomes, we need to consider both biology and socioeconomics. These disparities don’t come from one cause. It’s rather combination of differences in exposures, in biology, how healthcare systems operate. So let’s go one by one. So first, bladder cancer is thought of as a cancer of exposures. So the environmental exposures play a key role. While smoking is the biggest known risk factor, men and women tend to have different patterns of exposure. Historically, men have had higher rates of smoking, but then more women started smoking over the years, and that may have been a contributor. Although it’s not just one answer to this. Because when we look at the patterns of smoking and look at not just gender, but also racial differences, that’s not just the answer. So we also look at occupational hazards, which are also critical. Many men have traditionally worked in industries like manufacturing and construction. Exposure to carcinogenic chemicals is more common in these types of industries.

We are learning more about occupational risks in women, particular are more women enter these industries. There’s some other occupations that make women prone to cancer, like anything that has to do with the hair dyes. And one thing to remember, there’s a big latency period between the exposure and the cancer growing pretty much. So when we see these temporal trends, we have to look back many, many years. So if anything is changing, we’ll see this years later. Let’s talk about the metabolic pathways. This is the biological side. These pathways are different between men and women. There is some evidence that suggests that men and women process certain carcinogens differently. Which may influence how bladder cancer develops and progresses in each gender. Additionally, sex hormones are different in men and women, such as estrogen and testosterone. This can all affect the body’s immune response and tumor development. The estrogen may play a role in how all these genitourinary organs develop and how it responds to treatment. Although I don’t feel like we have enough knowledge to fully understand this connection. There is a lot more research that is ongoing and hopefully more to come.

Another emerging area of interest is the microbiome. When we say microbiome, this refers to the community of microorganisms living in and on our bodies. We never really appreciated microbiome until maybe recently, where we learned that these microbiota have… It’s like their own ecology within the body, and they affect a lot of the very, you would think, unrelated systems in the body, just by their presence and their activity. The bladder has its own distinct microbiome. This can potentially influence how bladder cancer behaves, how it’s initiated, and how it responds to treatment. It’s very possible, differences in the microbiome between men and women could also contribute to the disparities and also disease outcomes. This is a very exciting area, special interest for me, and a lot of other researchers are also interested in this area. Should get some further exploration to give us some answers.

Rick Bangs:

So this is a relatively new areas. At least as I understand it, because I think for years people thought that urine was sterile, and now we are talking about bacteria in the urine, but it’s not the normal kinds of bacteria, right?

Dr. Armine Smith:

Yeah, there is always bacteria in the urine. And when I studied medicine, I studied urology. We all thought urine was sterile. And the thing is, there are bacteria, but they’re at the very low levels. So when we try to do the traditional testing of urine with culturing, not everything grows. But when we do some specialized testing with in-depth instruments like PCR, where we just are able to extract these minute portions of nucleic acids, then we see a host of different bacteria that live in urine. It doesn’t make us sick. They just live there.

So the anatomy, if I can touch on this a little bit more, and then some of the socioeconomics also how it translates to our discrepancies. So the anatomy of the female bladder and surrounding organs are very different from men. You talked about urethra, but even just looking at the bladder, women have a thinner bladder wall, because they don’t need to push quite as hard to get the urine out because of the absence of the prostate and the urethra being shorter, this may make them more vulnerable to deeper tumor invasion. When we as urologists resect or remove a portion of the tumor from a female bladder, knowing that, I’ve seen many, many times that people tend to go a little bit shallower, trying not to perforate the bladder. So when the pathologists examine tissue samples from women, they often get less muscle in the samples, and that can lead us to underestimate the tumor’s severity or the depth of the invasion.

The incomplete sampling can contribute to misdiagnoses or delayed treatments for women or inadequate treatments for women. Adjacent organs play a significant role. We know that women with stage IVA tumors have worse outcomes, and that’s because, let’s say stage IVA tumors in women include invasion of the uterus and vagina, whereas the IVA stage tumor in men, involves prostate. And these organs have a different tissue thickness, like almost I would say padding. And they have a different blood supply which can also cause different patterns of metastatic disease. So this is all biology and anatomy. So on the top of these biological factors that there is the issue of later diagnosis in women. We alluded to it in the beginning, but women, a lot of the times have a delayed workup for hematuria. And that is because, number one, women are used to seeing blood in the urine.

They grew up with the menses, and it just does not cause quite so much of an emergency to run to doctor as when the menses blood in the urine. And then because of the presence of the gynecological organs, when the woman reports blood in the urine, a lot of the times it’s attributed to GYN issues, leading to referral to gynecologists, and sometimes multiple diagnosis of urinary tract infections and treatments, instead of timely referral to urologist and a bladder cancer evaluation. This delay in diagnosis means that by the time many women receive the correct diagnosis, the cancer may be more advanced, which also can contribute to worse survival rates. I’ll stop here.

Rick Bangs:

Oh no, this is fascinating.

Dr. Armine Smith:

Long-winded answer.

Rick Bangs:

This is really fascinating. So just curious about something. So we see more female primary care doctors than we had historically. Do we have any data that suggests that they do a better job of referrals to urologists or not? Maybe there’s not enough data yet.

Dr. Armine Smith:

I don’t think we have enough data, but when you look at these patients with their long-winded road to get to urologists, some women, just because they have these urgent care clinics that are quite convenient and very easy to get into, a lot of the times that’s the first pathway, right? So they see something and then they call in or go to the urgent care, or I don’t want to point out any places in particular, but this minute clinics people go to. And the reflex for these providers is to give her diagnosis of UTI and give them antibiotic. And then sometimes the culture is sent or may not be sent. Sometimes it’s a tele-visit. So that is a little bit more delay, little by little and it just adds up.

Rick Bangs:

Wow. We’ve already talked about some anatomical differences, and these not only have an impact on diagnosis, but they also have impact on treatment. And I know I’ve heard a lot about differences in radical cystectomy from the surgeon’s point of view. So I think you’re perfect person to talk about that from both the surgeon’s perspective, as well as the patient’s perspective.

Dr. Armine Smith:

Absolutely. I’m so happy you asked me this question. This is another area of my passion, for I think, this needs to be improved for women. So let’s talk about the radical cystectomy in women. Women have different anatomy, anatomical parts. They have uterus, ovaries, parts of vagina that are sitting right next to the bladder. These structures require careful consideration during surgery, particularly when we aim to perform these organ-sparing procedures. Historically, when bladder cancer was removed in women via radical cystectomy, urologists did something called anterior exenteration. Meaning, the whole front of the pelvis was cleaned out, including the vaginal wall, uterus, ovaries, fallopian tubes. Nowadays, we put a lot more thought into this, and the surgical approach needs to be meticulously planned to preserve as much of the reproductive anatomy as possible, and oncologically safe, while ensuring the complete removal of the cancer. From a surgical perspective, as a urologist, navigating these additional structures adds to the complexity of the procedure.

We as urologists, unfortunately, are mostly trained in the male pelvis because we treat prostate cancer and there are a lot more urological conditions that are male prevalent. So there is the familiarity with the pelvis, and we must balance the cancer control with the knowledge and trying to preserve the function while protecting adjacent organs, sparing nerves that are critical for urinary and sexual function. The nerve-sparing techniques in women, this is another new exciting development that is becoming more disseminating. These techniques can help maintain better postoperative outcomes such as preserving continence and sexual function. And these are all the things that are particularly important for women’s quality of life after surgery. Now from the patient’s perspective, the outcomes of radical cystectomy can also vary significantly based on the type of urinary diversion used. So not only just removal of the bladder now, reconstruction of the bladder. Women have the same options compared to men when it comes to urinary reconstruction.

Unfortunately, there are disparities in how these options are offered to these patients. For example, neobladder urinary diversion, such as what you have, where bladder is constructed from a portion of the patient’s own intestine, are sometimes not even offered to women from certain providers because of the outdated belief that neobladders do not function well in women. So this misconception denies many women the opportunity for a more natural form of urinary control, which can have significant impact on their overall quality of life. It’s crucial… Again, one area of my passion. It’s crucial that women undergoing radical cystectomy have access to specialists that are familiar with urinary diversions in them and the nuances or female anatomy. A surgeon who understands the intricacies of organ sparing, nerve sparing techniques is really vital in ensuring the best possible outcomes for women, both in terms of urinary continence and sexual health. And providing women with comprehensive information about the reconstructive options involving them in the decision-making process is really essential to improving post-surgical satisfaction, long-term outcomes. That’s another long answer to a short question for you.

Rick Bangs:

But it’s so fascinating. Because I’ve heard this myth about neobladders not being a good fit for women and you didn’t hear… You do now, but you didn’t necessarily hear about nerve sparing as it related to women. So these are all things that are important, as a female patient, these are all things to consider in terms of the procedure that I’m getting and the surgeon that I’m working with and the questions that I might ask. So, this is wonderful.

Dr. Armine Smith:

That’s correct, yep.

Rick Bangs:

Okay. So we talked about RC. Now, would there be differences in other treatments as a bladder cancer survivor, if I’m female, where anatomy and physiology might create differences? Because I already heard you talk about the TURBT and the fact that the bladder is thinner, so that gets a little bit trickier and has some nuances. But what other impacts on treatments might there be?

Dr. Armine Smith:

There are impacts on treatment that are gender-based. For example, treatments like intravascular therapies for non-muscle-invasive bladder cancer, may work similarly in men and women. But even simplistically, the anatomical differences such as bladder size, urethral length, the overactivity of the bladder, which is sometimes more prevalent in women, can influence how these treatments are tolerated. Women who have more overactive bladder and less padding, may not retain the intravascular agents quite as well as men do. Beyond that, another exciting development that we are learning more that, immune responses in women can differ between genders. So for example, immune response to BCG therapy, we have seen in some studies that women may exhibit a more robust initial immune response due to a distinct hormone environment and immune system dynamics, which can influence how their bodies react to this treatment. However, this heightened early response can also predispose the immune system to burn out over time, where the body becomes less responsive to this therapy after the initial surge.

Why is this happening? We don’t know quite yet, but we think it can be influenced by women’s microbiome history of recurrent UTIs that precondition their cells to be a little bit more ready to fight, but also depleting them more readily. And I alluded to microbiome, the community of microorganism residing in the bladder, it plays a potential significant role in modulating the immune response to a lot of the immunotherapies that we give. Women, especially those with prior UTIs, may have a different microbial composition. And again, the preconditioned immune system plays a role. We don’t know how the hormonal differences influence response to certain therapies, but again, we need more research in this.

Rick Bangs:

So many opportunities here. This is phenomenal from a research point of view. All right. You’ve clearly done considerable work in this area and you’re very passionate about it and you’ve got this wonderful vantage point. So we’re going to play a game here. So I’m going to grant you superpowers. And because we’re playing a game, these powers have absolutely no boundaries. So you control all the actions of all the stakeholders. And so when I say stakeholders, who do I mean? Government, doctors, nurses, insurance companies, patients, advocacy groups like BCAN and institutions, you’re going to have control over all that. And I’m going to give you the researcher’s favorite thing, which is an unlimited budget. So what changes would you make to remove these disparities and level the playing field?

Dr. Armine Smith:

Well, you see all these levels where we can make a difference. So I think starting with the primary care providers that are referring the physicians, first I would work on raising awareness among both patients and primary care providers about the unique presentations of bladder cancer in women. Again, to reiterate, women’s symptoms are frequently misattributed to urinary tract infections and some other gynecological reasons for bleeding, which leads to delayed diagnosis. So educating primary care physicians to recognize these symptoms early and start a appropriate referral for women to get them evaluated would be one crucial step in closing this diagnosis gap. The other thing is… And this is probably very difficult to implement, but this is, we’re talking about this utopia, right?

Rick Bangs:

That’s right. That’s right. Because you have superpowers.

Dr. Armine Smith:

That’s right. So I would ensure that women, especially those in underserved areas, have better access to tertiary care centers and clinical trials. Time and again, we see in a lot of these cancer, a lot of these disease states that this is one of the things that’s really crucial for treating this complex conditions. See, the tertiary specialized centers offer more advanced treatment options, innovative therapies that are not always available in the community settings. They have, let’s say, pathologists who are more trained to look at urological cancers, medical oncologists, or urological surgeons that are really very well versed in the advances in treatments. Expanding access to clinical trials is a big one. This would allow more women to benefit from these cutting edge treatments, improve our understanding of gender-specific responses to therapies. A lot of the clinical trials on bladder cancer have a lot more men than women.

And certain races are underrepresented or overrepresented. So an ideal situation would like to have a sample that cuts across all cohorts of the patients to know how we can improve the treatments for everybody. Another focus would be implementing, I would say, stringent criteria for bladder tumor resections. So which would be, let’s say the insurance or the payer to ensure consistency and quality across the board. And the urologist and pathologist need to follow standardized guidelines to ensure complete and accurate tumor removal, which can… I think it’s probably number one thing that can drastically impact long-term outcomes. And patients who start with non-muscle invasive bladder cancer, which is the two thirds of the bladder cancer we diagnose, or even more. So this would involve both better training or more rigorous oversight. And again, if it’s mandated, that is usually followed better. A lot of times we look at the pathology reports for bladder cancer, and there’s some crucial information missing.

The lymphovascular invasion, the stage of the tumor, these unusual histologies of the bladder cancer are not reported. And whether it’s because the training or the knowledge, these are the things that we can do better. I would allocate resources to better cancer counseling and education. I think we live at the day and age where every patient should receive some sort of multidisciplinary evaluation that their care is optimized from the outset. If we can create patient navigator programs, this would help guide patients through the complex healthcare system, try to get their timely care, get their appointments scheduled, try to make sure all the specialists are involved and the patients would feel supported throughout their treatment journey. And then I think, if we have the money, I would invest heavily in research. As you see, there are a lot of deficiencies we still are working on. We need to better understand the biology, environmental, and the systemic factors that contribute to the bladder cancer incidents, how it arises, how it’s treated, disparities, particularly in women.

By funding studies that explore areas such as microbiome, hormonal influences, immune system responses, which is kind of the new ear of the treatments, we can develop more personalized treatments and improve outcomes for everyone facing this disease.

Rick Bangs:

So now we’re back in the real world, and everything you’ve mentioned individually to me is just… It’s like the practical perspective. But as a total, maybe you’d have to have the superpowers to get all that done. So where do we start? What do we prioritize back in the real world?

Dr. Armine Smith:

I think we can start by this, I would call it more or less low-hanging fruit. Improving education, education of both healthcare providers and patients. We do need to ensure that primary care physician, gynecologists are aware of symptoms of bladder cancer, not just attributing them to more other common conditions. Trying to make screening a little bit more accessible, affordable, not prescribing antibiotics in women when there is no urine culture. It’s like a really low-hanging fruit.

Rick Bangs:

Even as somebody who’s not a doctor, that was like, “Really? We do that?”

Dr. Armine Smith:

We do it a lot.

Rick Bangs:

Yeah.

Dr. Armine Smith:

So on the patient’s side, I think public education campaigns can encourage women to advocate for themselves when they feel something is wrong. And advocacy groups like BCAN, which is a huge group that has contributed, played a critical role in offering resources and support, partnering with everybody else who we can bring to partner with us and help move the needle in the right direction.

Rick Bangs:

So now if I’m an individual woman or a man, either one, what do you think I could do?

Dr. Armine Smith:

I think it’s really crucial to advocate for yourself. It’s crucial for individuals to be proactive about their health. So if you notice any unusual urinary symptoms, blood in the urine, pain during urination, frequent urinary infections, please don’t delay seeing a healthcare provider. Advocate for yourself. Especially if you feel concerns are being dismissed. Educating yourself on the risks of the bladder cancer, particularly if you have a history of smoking, exposure to chemicals can be very helpful. Second opinions, I can’t stress enough. They’re always a good idea. And some people feel bad about going to another specialist to get a second opinion. And there’s nothing wrong with that.

Rick Bangs:

I’ve never heard… I’ve never talked to any patient… And not that I’ve talked to the entire population, but I’ve never talked to a patient that like, “Oh, I really regret getting that second opinion.”

Dr. Armine Smith:

Yeah. No, I think it’s major. But I feel like, especially some patients feel like they’re going to offend their urologist or they can’t go back and it’s just not true. And if your provider is offended by it, so what?

Rick Bangs:

Well, maybe you’ve got the wrong provider.

Dr. Armine Smith:

Exactly.

Rick Bangs:

If my doctor doesn’t want me getting a second opinion, I be kind of saying, “I don’t know. Maybe this isn’t the right place for me.” So now where can people go if they want to learn more about this subject?

Dr. Armine Smith:

Well, I think the Bladder Cancer Advocacy Network or BCAN is a fantastic resource for anyone looking to learn more about the bladder cancer. I refer my patients a lot to BCAN website, because the website offers both educational material, support groups, blogs, access to expert device. So I think that’s my go-to resource.

Rick Bangs:

Yeah, and I think, weren’t you on a webinar too recently?

Dr. Armine Smith:

I think I’ve done some webinars for BCAN, yes.

Rick Bangs:

Yeah. On this subject, I think.

Dr. Armine Smith:

Right.

Rick Bangs:

Wonderful. Wonderful. Okay. That’s wonderful. All right. And any final thoughts you want to share?

Dr. Armine Smith:

Yes. I would like to encourage anyone listening, whether you’re bladder cancer survivor, a caregiver, someone at risk to stay informed, and to take an active role in your healthcare. Also help disseminate the knowledge about the bladder cancer. I think early detection and prompt treatment are critical, and I think as a community we can together work to close these gaps and improve outcomes for everyone affected by this disease.

Rick Bangs:

Wonderful. Okay. Dr. Smith, this has been a fantastic podcast and I want to thank you for helping us better understand the needs and disparities of women facing bladder cancer and some potential actions that we can take.

Dr. Armine Smith:

Thank you, Rick.

Rick Bangs:

If you’d more information on bladder cancer, please visit the BCAN website, www.org. In case people would like to get in touch with you, could you share an email address where they might be able to reach you?

Dr. Armine Smith:

Absolutely. You can email me with any questions. My email is [email protected].

Rick Bangs:

Excellent. Thank you. Just a reminder, if you’d like more information about bladder cancer, you can contact the Bladder Cancer Advocacy Network at 1-888-901-2226. That’s all the time we have today. Be sure to like, comment and subscribe to this podcast so we have your feedback. Thank you for listening, and we’ll be back soon with another interesting episode of Bladder Cancer Matters. Thanks again, Dr. Smith.

Dr. Armine Smith:

Thank you, Rick.

Speaker 1:

Thank you for listening to Bladder Cancer Matters. A podcast by the Bladder Cancer Advocacy Network, or BCAN. BCAN works to increase public awareness about bladder cancer. Advanced bladder cancer research, and provide educational and support services for bladder cancer patients. For more information about this podcast, and additional information about bladder cancer, please visit bcan.org.