Uterine Cancer: Symptoms, Diagnosis and Treatment Options

Podcast Transcript

Erica Newlin, MD:

Welcome to Ob/Gyn Time, a Cleveland Clinic Podcast covering all things obstetrics and gynecology. These podcast episodes are intended to help you better understand your health, leaving you feeling empowered to live your best. We hope you enjoy today's episode.

Hi, everyone. I'm your host, Dr. Erica Newlin. Welcome to Ob/Gyn Time. During this season, we are focusing on topics related to gynecologic oncology, meaning cancers of the female reproductive organs. On this episode, I'd like to welcome Dr. Anthony Rizzo, who'll be talking to us about uterine cancer.

Dr. Rizzo, thanks so much for joining me on the podcast.

Anthony Rizzo, MD:

Thanks for having me, Erica.

Erica Newlin, MD:

Can you tell us about your role in the Cleveland Clinic, and a little about your background?

Anthony Rizzo, MD:

I'm a member of the Gynecologic Oncology division. I joined the clinic about two years ago after finishing my training in gynecologic oncology at University Hospitals. I work primarily in the southern region, with most of my patients coming from around the Akron and Canton areas.

Erica Newlin, MD:

Great. And let's start by clarifying anatomy. Where is the uterus, and what purpose does it serve?

Anthony Rizzo, MD:

That's a great starting point. So the uterus is a reproductive organ in the female pelvis. It carries the fetus during pregnancy, so it's often colloquially referred to as the womb. It includes the cervix, which is what dilates during labor, and it resides at the internal end of the vagina. The fallopian tubes and ovaries sit on either side of it. Outside of pregnancy, the uterus and ovaries are part of the menstrual cycle. It produces menstrual blood during a woman's menses. And the uterus has three layers, which will become important in our discussion. The internal layer is what carries a pregnancy, often called the endometrium. The muscular layer, which is next, is called the myometrium. And then the outer layer, which faces the rest of the abdomen and pelvis, is called the serosa.

Erica Newlin, MD:

Yeah, and that brings us to our next question. Are there different types of uterine cancer based on those different areas of the uterus?

Anthony Rizzo, MD:

Certainly. Often, people when they think of uterine cancer, will refer to endometrial cancer, which is one type of uterine cancer. Both are a correct way to describe it, but when you talk to your gynecologic oncologist, or if you're diagnosed with a uterine cancer, you may find that there is many more types of uterine cancer. And, you know, for most people, you don't have to worry about those differences, but when we talk about each person, those differences become important. So, generally, we can break the cancers down by where they arise from within the uterus, and then even more than that, when we look at them under the microscope, or we get additional testing, and we can classify them further.

Erica Newlin, MD:

And would it be correct to say that there's different treatments based on where exactly in the uterus the cancer arises?

Anthony Rizzo, MD:

Certainly. Where the cancer arises and how it may behave will dictate how we design a treatment plan for each person.

Erica Newlin, MD:

Sure. And are there certain people more at risk for uterine cancer?

Anthony Rizzo, MD:

Well, any person who has a uterus is at risk for uterine cancer. For the most part, uterine cancers are diagnosed later in life. So, people at advanced ages are going to have a higher risk of developing a uterine cancer. Certain types of uterine cancer can be associated with different risk factors. Certainly overexposure to estrogen, for one method or another, will increase risk of endometrial cancer specifically. But other uterine cancers, really the only risk factor is being either perimenopausal, around the age of menopause, or post menopausal.

Erica Newlin, MD:

And what kind of situations might put someone at a higher estrogen level that might make them higher risk for endometrial cancer?

Anthony Rizzo, MD:

So certainly, at all stages of life, taking additional estrogen can put someone at increased risk. You know, interestingly, the estrogen that's given with birth control pills is not an excess of estrogen because it's often balanced by the progestin in it, so that doesn't really qualify. But if someone is using hormone replacement therapy, that can certainly be a risk factor. Certain medications like Tamoxifen, which are estrogenic can also be a risk factor. Certain conditions like polycystic ovarian syndrome or other things that cause an imbalance in how a person has a cycle every month can also increase estrogen exposure. And then finally, unfortunately carrying excess weight in the form of adipose tissue can be a really challenging risk factor, both to modify-

Erica Newlin, MD:

Mm-hmm.

Anthony Rizzo, MD:

... and to plan for, because just having the weight is not necessarily going to increase your risk, but certainly it makes us worry. And if, you know, your bleeding pattern isn't evaluated or monitored by an OB/GYN or your primary care, certainly that risk can go up.

Erica Newlin, MD:

Sure. And does family history play any role in risk for uterine cancer?

Anthony Rizzo, MD:

Family history is a very interesting risk factor. For most uterine cancers, there is not a hereditary component, but there are certain familial syndromes, and interestingly, they're shared with a family history of colon cancer. So individuals with a family history of uterine cancer or colon cancer definitely should discuss this with their physicians because we do have helpful screening if someone is, you know, at high risk based on that history, and we can often modify that risk.

Erica Newlin, MD:

Perfect. And then what symptoms would raise suspicion for uterine cancer?

Anthony Rizzo, MD:

Uterine cancer is interesting in that vaginal bleeding can be a warning sign, but not all vaginal bleeding needs to sort of raise the alarm bells. I think the most important thing is if vaginal bleeding is getting heavier or occurring after menopause, those would be the most worrisome signs. But really any abnormal vaginal bleeding I think should trigger a discussion with someone's primary care or OB/GYN, because even though most abnormal vaginal bleeding is not caused by cancer, it can be, you know, something that we can help you with. And certainly since it is a warning sign for cancer, it should be evaluated, hopefully promptly.

Erica Newlin, MD:

Sure. And if someone does raise those concerns about their bleeding to their physician, what kind of work up might be prompted, and how would uterine cancer be diagnosed?

Anthony Rizzo, MD:

It's really individualized for each patient. It depends on where they are in their life, either, you know, thinking about their reproductive goals, or maybe they're post menopausal. In most cases, the first step is going to be an exam with their doctor. Because as I said, uterine cancer is not the only thing that will cause vaginal bleeding. So an exam is often helpful to start ruling things in or out. The next steps are often potentially an ultrasound of the pelvis, which in most cases, it's helpful if that can be transvaginal. But again, at different stages of life, that can be more challenging. And then often, particularly is someone is post menopausal, an endometrial biopsy, which is a procedure that's often conducted in the office, relatively quick, sometimes uncomfortable, but we can manage that in most cases, is often the next step to help either evaluate for uterine cancer, or to obtain the diagnosis.

Erica Newlin, MD:

So, just to summarize a lot of this work up can be done by a general gynecologist to start off with. So if you have any concerns about your bleeding, you can go to your general OB/GYN and make sure to mention these things at your annual visit.

Anthony Rizzo, MD:

Certainly. And I think since often by the time a patient is seeing a gynecologic oncologist, you know, just having the word "oncology" in our title I think invites a lotta concern and anxiety, so knowing that a lot of vaginal bleeding is not going to be caused by a uterine cancer I think puts people at ease to start this conversation with someone who can evaluate for all the possibilities very efficiently, and often without that sort of fear hanging over someone's head.

Erica Newlin, MD:

For sure. And that does bring us to our next question, which is, if someone has received a diagnosis of uterine cancer, and is preparing for their visit with a GYN oncologist, what could they expect for next steps of work up? Is there a particular imaging or blood work they can expect? Again, respecting that it's probably individualized per patient.

Anthony Rizzo, MD:

Mm-hmm. I think, again, when you first meet with your gynecologic oncologist, the most important pieces of that work up are, you know, interviewing a patient, getting to know them and their circumstances, followed by an exam. Because while we often work closely with our general OB/GYN colleagues, there are some nuances that might be different when we're examining a patient. So I often, I try to help patients understand that, you know, the multiple exams is not because we're seeing something different necessarily, but because we're evaluating slightly different things. When your gynecologic oncologist sees you, the exam is to help them understand the anatomy, and to plan for a potential surgery or other treatments. Whereas, when your general OB/GYN is examining you, their priorities are a little bit different, getting a diagnosis or potentially getting a biopsy done.

Following that, you know, initial evaluation with an exam and an interview, in many cases, additional imaging may not be needed, but in some cases it will be. And that really is going to be decided by the patient with their gynecologic oncologist, because it's an individualized discussion. In most cases, additional imaging might include computed tomography, or CT scan, or in some cases, magnetic resonance imaging, or MRI scan. And both of those are to help us understand whether or not a cancer might have spread outside of the uterus, or to get some idea of that risk. Because that's one of the first decision points where we might modify a treatment plan.

Erica Newlin, MD:

And we've spoken a little about cancer staging in prior episodes, and recognizing it can be a very complicated system, do you mind recapping, what does cancer staging mean, and how is uterine cancer staged?

Anthony Rizzo, MD:

Certainly. So let's start with cancer staging. Cancer staging in general defines where a tumor is inside of a patient's body, and whether or not it has spread from a primary organ. In most cases, that information is useful prognostically first, we then use that information to help us tailor treatments down the line. But thinking about prognosis, what that would mean generally is that a stage one tumor, which would be considered earlier, will have a better prognosis than a stage three tumor even though both may be treatable, and in some cases, curable. But what is necessary to achieve that treatment plan will change based on that stage. Uterine cancer is interesting because we have learned a lot about uterine cancer in the last 10 to 15 years very quickly as more robust molecular information has been gathered. And so uterine cancer is not necessarily staged only by where it resides in the body, sometimes it has to do with those different types that I was alluding to earlier. A lot of that is minutia that, you know, patients may not want to wrap their head around initially-

Erica Newlin, MD:

Mm-hmm.

Anthony Rizzo, MD:

... and that's okay because that's what we're there for, to help people understand that, and to walk them through that. But certainly staging is one of several numbers people may see when they look at their pathology reports. And so I think most of us try to be a guide for people to understand that information.

Erica Newlin, MD:

And can you discuss when surgical treatment of uterine cancer would be the recommended treatment?

Anthony Rizzo, MD:

Certainly. So, one of the better things about uterine cancer is that the majority of them are actually diagnosed at an early stage, so typically stage one, confined to the uterus. And what that generally means is that surgery can play a very large role in achieving cure for a majority of patients. And that does not mean all, and certainly even some patients who cancer is not limited to their uterus, so stage two or higher, may be a candidate for surgery to start. But often, early disease, surgery's going to play the primary role, and that's because surgery also affords the opportunity for staging. Staging in uterine cancer is based on pathologic evaluation, so organs come out and we look at them under the microscope, and that helps us assign a stage.

Erica Newlin, MD:

Great. So, usually when we're talking about surgery, we're talking about a hysterectomy, so removing the uterus, and then can you talk a little about the role of lymph nodes? What are lymph nodes and where do they come into play?

Anthony Rizzo, MD:

Certainly. So staging for uterine cancer includes a hysterectomy, which is removing the uterus and cervix. That can be done through a variety of means, one big incision on the abdomen, several small incisions, often called laparoscopy or minimally invasive surgery, sometimes with robotic surgery, which is a variant of laparoscopic surgery. In addition to that, staging includes removing both fallopian tubes and both ovaries, because that's one of the places that uterine cancer can spread to. And then as you mentioned, the lymph nodes are evaluated. And that is something that, again, can be individualized for each patient, but in general, lymph node evaluation provides more information for prognosis because it gives us more definitive staging information. We're able to evaluate those lymph nodes under the microscope, and sometimes catch cancer that has spread microscopically, even only a few millimeters to those lymph nodes, which can make a big difference in how we would recommend additional treatments for those patients.

In general, we recommend sentinel lymph node evaluation for most patients now who have the most common type of uterine cancer, which is endometrial. But sentinel lymph node surgery is not appropriate for every patient with uterine cancer, and so that's something that we individualize in the discussion.

Erica Newlin, MD:

We've spoken about uterine cancer as primarily affecting women that are a little older in their lifespan, but are there options for younger women who may want to retain their childbearing options?

Anthony Rizzo, MD:

Certainly. So that is always a very difficult question to answer, and of course very unique and individualized for each circumstance. In general, uterine cancers that affect younger women tend to be those that can be treated with hormones in some cases as a way of preserving the uterus until someone can be done with childbearing. But that's not appropriate for every patient, and in cases where the patient and the provider decide to not proceed with a uterine preserving treatment option, we can often discuss preservation of ovaries, which would allow someone to have their own genetic child even though they would have to use a surrogate to carry that child.

I would say that in some cases where we worry that the patient's, you know, treatment and survival from the cancer is gonna be significantly compromised, we make every effort to meet patients where they're at with their goals, and that that's a multidisciplinary discussion often involving our colleagues from the reproductive endocrinology side of OB/GYN, and even a patient's general provider sometimes. Because often with these treatment plans, a lot of close follow up is necessary, and maybe you don't have to see your gynecologic oncologist for every visit. So these are really multidisciplinary plans that we make in those situations.

Erica Newlin, MD:

Sure, and we've talked about in previous episodes that if that is a concern regarding future fertility to bring that up early in the process-

Anthony Rizzo, MD:

Certainly.

Erica Newlin, MD:

... so we can involve our infertility specialist as well. When would first line treatment not be surgery for uterine cancer?

Anthony Rizzo, MD:

There are basically two main categories where we would discuss surgery as either a secondary or not an option at all. First would be if we have concern that the cancer has spread outside the uterus, and is not something that can be safely removed with an appropriate risk of recovery from that surgery. For example, if cancer has spread to someone's lungs, from the uterus to the lungs, that's not something that I think any of us would recommend starting with a surgery because the risk is that if it's in one spot outside the uterus, it could be in multiple. And we don't want to do a surgery that's going to compromise someone's recovery to the point where we can't give a more effective treatment, which in that case would be systemic, going everywhere in the body. That's often chemo or immunotherapy.

So that's the first situation where surgery may not be the first step. Some sort of biopsy may play a role, and often these are things that we would find on that CT scan or potentially MRI because similarly, if cancer has spread within the pelvis, say to involve a bladder or the rectum, often we may not start with surgery because that can be a very difficult surgery to recover from, and can compromise someone's normal stooling or urination, which are not changes that most people are expecting when they're being treated for a uterine cancer. So in those situations, we'll either start, as I said, with chemo or immunotherapy, or in some cases, start with radiation, in situations where it's locally advanced within the pelvis.

And then in cases where a patient is medically not safe to proceed with a surgery, 'cause this is considered a major abdominal surgery, we might recommend treatment with either chemotherapy, immunotherapy, or radiation, instead of surgery. In those cases, often patients' other medical problems, for example, things like cirrhosis, very, very serious heart or lung disease might be more risk than the surgery itself that we're contemplating, and so those treatments with chemotherapy, immunotherapy, or radiation can actually offer the same survival benefit by avoiding that risk of surgery. And so we make that sort of trade off. Those are very individualized discussions, and certainly a lotta questions need to be explored before a patient might feel comfortable with that, or a provider might feel comfortable recommending it. Those tend to be longer work up experience for patients, and a lot of anxiety associated, but ultimately that is often the safer way to proceed in those situations.

Erica Newlin, MD:

Sure. And on the other hand, in patients who have undergone surgery for their uterine cancer, how do you decide who needs additional treatment in addition to surgery?

Anthony Rizzo, MD:

That's a great question, and I think in general is one of the areas of our field that's changing fastest. Certainly with the introduction of new chemotherapy drugs, new radiation techniques, we get better and better at deciding who needs additional treatment, and balancing the risks from that additional treatment. In general, once you have your surgery, we have a wealth of information from that microscopic evaluation, and that assigning of a stage. For cancers that have spread outside of the uterus, generally we will recommend some type of additional treatment. In many cases, it's systemic therapy, or chemo, or immunotherapy. In some cases, even for cancer that is confined to the uterus, we may still recommend that systemic therapy, or we might recommend a course of radiation therapy. And that type of radiation can be very different based on those more nuanced factors.

Erica Newlin, MD:

And that brings us to our next question. Generally, what is the role of radiation and what does that look like in the treatment of uterine cancer?

Anthony Rizzo, MD:

I definitely think you could have a radiation oncologist on here to give a much more detailed-

Erica Newlin, MD:

We do (laughs).

Anthony Rizzo, MD:

... oh (laughs), much more detailed answer to this.

Erica Newlin, MD:

Yeah.

Anthony Rizzo, MD:

But in general, we think about radiation sometimes in the primary treatment of uterine cancer for people who are not medically fit for surgery, and that's often given from outside the body, beams of radiation directed towards the pelvis. For patients who have had their surgery, and we think that radiation will help lower the risk of the disease coming back, that can be given either as radiation from outside the body or from inside the body, called brachytherapy, targeting the vagina, which is one of the most common sites of recurrence for uterine cancer. And then finally, often we use radiation in the treatment of recurrent uterine cancer, either within the pelvis or in other sites of the body, because we can deliver a very focused dose that can help reduce the side effects that metastatic disease might cause.

Erica Newlin, MD:

And then moving onto chemotherapy, respecting that it's likely individualized per patient, in general, what does chemotherapy look like for the treatment of uterine cancer?

Anthony Rizzo, MD:

Sure. So in general, systemic therapy, which is chemotherapy or immunotherapy, 'cause we are using immunotherapy much more frequently in patients who have advanced uterine cancer, it consists of an IV infusion. Those drugs are given once every three weeks, and most commonly side effects that, you know, even though the drugs may be different for each circumstance, fatigue, often hair loss, changes in appetite or electrolytes and dehydration will go with pretty much any chemotherapy regimen we recommend. Other types of side effects unique to the drugs that are given will have to be a more individualized discussion.

Erica Newlin, MD:

And you've touched on this a little by mentioning immunotherapy, but are there any other additional treatments that may be used for uterine cancer?

Anthony Rizzo, MD:

Well we have many types of new drugs coming on the market very soon. In many cases, these are for more advanced or recurrent disease, which is a good thing, we don't have too much of that. But those drugs are technically chemotherapies, but they're designed a little bit differently. And so you may hear the term "antibody-drug conjugates", and those are more targeted therapies that we hope are going to be a better balance of the risk of the treatment with the benefit that they cause because they target the cancer cells specifically.

Erica Newlin, MD:

Great. Any other promising treatments on the forefront that may change how we're treating uterine cancer?

Anthony Rizzo, MD:

Personally, I think the most promising development is our better understanding of the molecular types of cancer. So we're, we're more understanding that uterine cancer may be, you know, tens or hundreds of different diseases when we get down to their genetic makeup, and more and more we're understanding how we can tailor our existing treatments that work quite well to give them to the patients who are going to need them. And so that's a double-edged sword. We're both treating the right patients with the right treatments, and we're going to hopefully remove the side effects that we cause by over treating another patient population. It's very early stages, and we're just starting to understand how molecular characterization can refine our prognostic information.

Erica Newlin, MD:

Sure. And then for people who have completed treatment for their uterine cancer, what does surveillance look like?

Anthony Rizzo, MD:

So surveillance for uterine cancer generally involves visits with either your gynecologic oncologist or your general obstetrician gynecologist every three to six months for the first two years. At those visits, you'll discuss symptoms that we worry about, things like vaginal bleeding, changes in your appetite, or abdominal pain. Then you'll have an exam, 'cause again we're looking at the vagina as a potential source of recurrence.

In some cases, those visits will trigger additional work up, like an imaging with a CT scan, or maybe a PET scan. Often, those things are not necessary, but those would typically be the next steps. After about two to three years, that regimen changes, and we start seeing you about every six months. And then after five years, we would see you annually. And the reason for that is that most uterine cancers will have a recurrence within the first three years, and then it, it starts to taper off after that. It's always important for someone who's had a uterine cancer, I think, to maintain a relationship with someone who they can talk to about gynecologic complaints, or can do an exam with them, because often that's something that's hard to meet someone out of the blue and get evaluated. But I also think it's important for us in the medical field to feel more comfortable discussing women's health problems. And so we can work at that from two angles.

Erica Newlin, MD:

For sure. And as we come to a close, what would you recommend or say to someone newly diagnosed with uterine cancer?

Anthony Rizzo, MD:

What I often tell my patients the first time I meet them is they're starting a journey, and uterine cancer in particular, everyone's journey is going to be a little bit different. That's probably true for every cancer. It's important to have some people who are going to go on that journey with you. Your gynecologic oncologist can be one of them, but really any person in healthcare or in your life that you trust can go on that journey with you. It's a lot of information to digest and process, and it's a lot to put your body through, but we're help guide and help you along that way.

Erica Newlin, MD:

Perfect. Well, thanks so much for joining us, Dr. Rizzo. It's been a pleasure.

Anthony Rizzo, MD:

Thank you. I've enjoyed it.

Erica Newlin, MD:

Thank you for listening to this episode of Ob/Gyn Time. We hope you enjoyed the podcast. To make sure you never miss an episode, subscribe wherever you get your podcast, or visit clevelandclinic.org/obgyntime.