Endometrial Carcinoma
Endometrial carcinoma. Endometrial carcinoma is the most common type of uterine cancer (accounting for more than 90% of uterine cancers).1
Uterine carcinosarcoma (UCS). UCS has been classified as a high-grade endometrial cancer.2 Although UCS accounts for only 5% of all uterine tumors, it accounts for 15% of deaths caused by uterine malignancies.2
Classification of endometrial tumors is based on histologic subtypes. These subtypes are broadly termed type 1 or type 2 and are based on clinical and pathologic features.3
Incidence in the United States
Endometrial cancer is the most common gynecologic malignancy in the developed world.5 In 2023, it was estimated that 66,200 cases of endometrial cancer would be diagnosed and 13,030 individuals would die from the disease in the United States.1
Epidemiology in the United States
From the mid-1990s, mortality rates for uterine cancer rose steadily, with a 0.7% annual increase from 2016 to 2020.1 Most patients with uterine cancer (67%) present with localized disease and have a 5-year survival rate of 95%.6 However, in patients with regional (20%) or distant (9%) metastasis, 5-year survival rates decrease to 70% and 18%, respectively.6
Risk Factors
An estimated 70% of uterine corpus cancers may be attributable to a lack of physical activity and excess body weight.1 Obesity can increase the amount of circulating estrogen, which is a strong risk factor for disease.1 Additional factors that may contribute to risk of uterine cancer include exposure to postmenopausal estrogen alone, late menopause, and a history of polycystic ovary syndrome.1 Medical conditions such as Lynch syndrome and type 2 diabetes may also be associated with increased risk.1
Unmet Need
Racial disparities remain among those with uterine cancer.1 Black patients are more likely than White patients to have advanced-stage or unstaged disease (44% vs 29%, respectively) and experience lower rates of 5-year survival (64% vs 84%, respectively; data from 2012-2018).1
References: 1. American Cancer Society. Cancer Facts and Figures 2023. 2. Cantrell et al. Gynecol Oncol. 2015;137:581-588. 3. Mendivil et al. Cancer Control. 2009;16:46-52. 4. American Cancer Society. What is endometrial cancer? https://www.cancer.org/cancer/endometrial-cancer/about/what-is-endometrial-cancer.html. Accessed October 19, 2022. 5. Raglan et al. Int J Cancer. 2019;145:1719-1730. 6. National Cancer Institute. Surveillance, Epidemiology, and End Results Program. Cancer Stat Facts: Uterine Cancer. https://seer.cancer.gov/statfacts/html/corp.html. Accessed September 1, 2022.
Resources
Screening Procedures in EC
Early detection of endometrial cancer (EC) may allow for early treatment...
and an improved prognosis. Here, Floor Backes, MD, and David Miller, MD, describe their experiences with screening for EC and their thoughts on the importance of early symptom detection and screening practices.
Click to expand transcript
[Dr. Backes]: We typically do not do screening or genetic screening at
the initial diagnosis. Absolutely, we want to have all patients ultimately
tested for at least Lynch syndrome, which is associated with a change in
mismatch repair proteins. So at our institution, we usually do this on the
hysterectomy specimen, but it is certainly possible to do this on the initial
endometrial biopsy, from either an office endometrial biopsy or a D&C,
and already get that initial screening done. So that's an important one
for future therapies, but also to diagnose patients or screen a patient if
they could have this endometrial cancer as part of Lynch syndrome.
Then, they can use preventative measures for family members, but also
preventative measures for other malignancies that they may develop
over, or at risk for, over their lifetime.
[Dr. Miller]: Unfortunately we don't have a screening test similar to a
Pap smear for endometrial cancer. So that's why it's important for us to
pay attention to early symptoms like we've already talked about,
abnormal bleeding, post-menopausal bleeding. We can identify a few
patients at risk who have been previously identified through our genetic
counselors and genetic screening as a consequence of other family
members having some sort of cancer. But again, we don't have a
screening test to help us yet—prevent endometrial cancers. If we pay
attention to symptoms, we're going to find the vast majority of those
endometrial cancers.
The Challenges With Molecular Classification in EC
The rise of molecular classifications in endometrial cancer (EC) may facilitate...
addressing unmet treatment needs for patients, but there are some challenges. Here, Floor Backes, MD, and David Miller, MD, share their thoughts on EC classification.
Click to expand transcript
[Dr. Miller]: So this is an evolving, rapidly evolving field for which the answer
may be a little bit different next year. But we have a number of different
schemes by which we can sort of triage endometrial cancer tissue to help us
identify what type of tumor the patient might have. We're now developing
trials, which may allow us to see if that molecular classifier can apply to
early-stage disease. And we have particularly some very appealing studies
where we may even be able to de-escalate our previous interventions,
maybe give the patient less therapy. For example, if a patient has a so-called poly hyper mutated patient, those patients do very well. Now, do
they do very well because they're poly hyper mutated or have we just been
treating them really well? And they respond to the things we usually do.
We don't know the answer to that yet, but we’re asking the important--we
hope to ask the important question of, well, maybe we can give them less
treatment, maybe less radiation or less chemotherapy. We still think surgery
is necessary. And so these, these molecular findings are informing our
therapies and we anticipate that they will be more informative as time goes
by.
[Dr. Backes]: Yeah, so Dr. Miller mentioned a couple of the different
classifications, and we really have been lucky that some of our colleagues in
Europe, as well as in Canada--in Canada with the ProMisE algorithm and in
Europe, through the PORTEC Alliance there--that they have kind of sorted
out these different populations. And Dr. Miller mentioned poly already as a
sub-classification that does well. We talked a little bit about mismatch
repair deficient category, and then we also have the copy number high or
more serous-like tumors and the no specific mutational profile category that
we know of.
Risk Factors in EC
Endometrial cancer (EC) has numerous risk factors. Here, Floor Backes, MD,...
and David Miller, MD, explain one of the major risk factors for EC as well as the correlation between obesity and EC.
Click to expand transcript
[Dr. Miller]: Well, the factors that increase the risk of endometrial cancer,
unfortunately, are similar factors that increase the risk of many diseases in
our society. And probably the leading controllable risk factor is obesity,
which increases the risk of many diseases, but it increases the risk of
endometrial cancer. There are some potential strategies that might mitigate
that. We know that if we do interventions for patients that we can improve
the risk of, or help patients not approach, obesity through various
interventions, whether those turn into actual therapies for endometrial cancer
will remain to be seen. But that's probably our biggest sort of controllable or
modifiable risk factor right now.
[Dr. Backes]: Dr. Miller already mentioned about obesity, weight loss. But
also, when we think about those patients that are overweight, and increased
estrogen exposure may play a role in more so in those patients. We think
oftentimes about low grades, grade-one endometrial cancers. And so in
those patients, other than our traditional chemotherapy, certainly they're
candidates for now a more wide array of therapies, but we also have to
remember that hormonal therapy may be effective for these patients as well.
So, and much more so in those low-grade tumors compared to high-grade
tumors, and we see that in this population particularly.
Predictors for Disease Advancement
Recurrence of endometrial cancer (EC) may be more common in certain...
patient populations. Here, Floor Backes, MD, discusses what predictors may increase the likelihood of recurrence.
Click to expand transcript
[Dr. Backes]: So the thought is currently that those patients with a mismatch repair deficiency do have a higher risk of recurrence, but we also know that compared to, for example, the grade ones, more advanced or more the grade-three tumors have a higher risk of recurrence. Patients with clear cell or serous cancers of the uterus, patients with uterine carcinosarcoma. Those are all much higher risk of recurrence and not just a local recurrence, but particularly also a distant recurrence, which is much more difficult to treat and, and very hard to cure, if possible at all. So, it definitely impacts how we manage these patients and also how we--what kind of treatments we recommend for those patients.
Postmenopausal Bleeding in Gynecologic Malignancies
Endometrial cancer (EC) can present in various forms. Here, Floor Backes,...
MD, and David Miller, MD, discuss the different patient types commonly seen in EC and how they factor into individual prognosis and risk levels.
Click to expand transcript
[Dr. Miller]: Well, I guess the good news and the bad news: the bad news, the
patient might have endometrial cancer. The good news is for the vast
majority of patients, it presents with symptoms, most characteristically post-menopausal
bleeding. And again, the stereotypical patient with endometrial
cancer is a patient who is obese, has some history of exposure to unopposed
estrogen, and that's sort of the good group of endometrial cancer patients
that we've recognized for decades. But there's also the group of endometrial
cancer patients who have the more higher [sic] risk types of endometrial
cancer, such as serous tumors. Fortunately, those too usually present with
symptoms, but they don't fit into a specific morphology that we tend to
stereotype endometrial cancer patients.
[Dr. Backes]: Most patients do present with the post-menopausal bleeding, but
we also sometimes see those patients that have had, cervical stenosis or
something like that, where patients do not necessarily present with cervical
cancer until it becomes metastatic to the cervix, vagina, or other areas. And
in those patients, sometimes we see much more advanced disease without
post-menopausal bleeding. And that is absolutely worrisome but absolutely
the majority of the patients, fortunately, presents with bleeding and can be
diagnosed early and treated effectively with surgery.
Racial Disparities in EC
Gynecologic health is an important topic in Black communities, where the...
incidence of endometrial cancer (EC) may be higher. Here, Floor Backes, MD, and David Miller, MD, share their thoughts on racial disparities in EC.
Click to expand transcript
[Dr. Miller]: We know that African American women, for example, appear to have a higher
incidence of some of our worst histology endometrial cancers, such as serous tumors and
carcinosarcomas. And in a number of different studies, they tend to have worse outcomes,
and then the issue is why, why is that? Is the tumor biology for those patients different? Is it
an access-to-care issue? Is it some sort of discrimination issue where they're not able to
access interventions that make a difference? It's a very complex problem that we need to
deal with.
[Dr. Backes]: And it's really important that we study this more and figure out are these
patients—are these changes in the tumors? Where are those coming from, how can we best
treat them, and do we need to treat some of these underlying molecular changes also
different [sic] for these tumors and these patients? Education I think, is also very important,
because in certain subpopulations, it is not as well known that post-menopausal bleeding is
not a normal thing. And so oftentimes also then gets ignored because “my mom and my
grandma had this, too, and so it must be normal.” But also improve just the awareness of
endometrial cancer of post-menopausal bleeding and early symptoms, so that we can
diagnose patients also earlier, rather than at advanced stages where the outlook is much
more difficult and treatments are much more difficult to get optimal results and cure.
Educational Gaps in EC
There are various educational gaps in endometrial cancer (EC). Here, Floor...
Backes, MD, and David Miller, MD, share their thoughts on what they believe to be the biggest educational gaps for physicians seeing patients with EC today.
Click to expand transcript
[Dr. Miller]: Our biggest educational gap is keeping up with the new
developments we have, just within endometrial cancer. A significant increase
in the application of molecular biology to actual treatment of patients. And
helping our colleagues, ourselves, keep up to date on that information, how
we can apply that information to, to our patients. So, education is very,
very, very important. If you're not up to date, you're not going to help your
patient as much as you could.
[Dr. Backes]: Yeah, and what Dr. Miller said, “Oh, you have endometrial
cancer, so this is a treatment you didn't have.” Then we said: “You have a
type one or a type two endometrial cancer, more a low-grade or a higher
grade.” And we started making some shifts in that. Then we go to these
different subcategories. And we're going even a step further now where
we're looking for certain mutations.
[Dr. Backes]: And even more important than just having education out there is
probably also finding time for education, because that is another one in the
current environment. There's so many things and things that we have to all
do, credentials and certifications and email and electronic medical records,
that just sitting down to take time to learn and to catch up and to go
through the education is another challenge, I think, that all health care
providers and team members are facing.
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