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Gynecologic cancer

Gynecologic Cancers:
Endometrial
Carcinoma

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

  • Type 1 tumors include grade 1 or 2 endometrioid adenocarcinomas.4 Endometrioid carcinomas are the predominant subtype and account for approximately 80% to 86% of endometrial cancers.3
  • Type 2 tumors include all endometrial carcinomas that are not type 1, such as papillary serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, and grade 3 endometrioid carcinoma.4 These cancers are poorly differentiated in histology.4

    • 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.

    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.

    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.