Rewriting the Prognosis: Advances in Endometrial Cancer Diagnosis and Treatment

ReachMD Announcer:
You’re listening to Project Oncology on ReachMD. On this episode, we’ll hear from Dr. Kathleen Moore, who’s a gynecologic oncologist and the Director of the Oklahoma TSET Phase I Program at OU Health Stephenson Cancer Center in Oklahoma City. She’ll be discussing how our approach to treating endometrial cancer has evolved. Here’s Dr. Moore now.

Dr. Moore:
I'm very happy to say that the treatment landscape for patients diagnosed with endometrial cancer is changing, and what is true today will likely change next year and beyond and that's very good.

Just to level set, most patients with endometrial cancer are diagnosed at early stage because often, postmenopausal bleeding that occurs is recognized as abnormal and patients seek care. And we can, in many cases, cure endometrial cancer with a surgery alone with or without some adjuvant radiation. But we are seeing alarming trends in that endometrial cancer is either the only or one of the only solid tumors increasing in both incidence and mortality and largely at the expense of people of color. And in addition to that, we're seeing a trend towards younger women being diagnosed with endometrial cancer similar to what we see in colorectal cancer, disproportionate number of people of color and higher-risk histologies.

So while it is true that endometrial cancer can be diagnosed early and cured with early intervention, we still see an increasing number of people presenting either with advanced-stage disease or disease that is, even though lower stage, very high risk for recurrence. And over the decades prior to this, we have tried to intervene in that early stage, local regional spread we know of high risk recurrence with a variety of things different types of radiation, adding chemotherapy with or after radiation, and have developed a number of risk stratification algorithms to try and identify these patients. And the truth is that none of it worked very well. We still have patients who recur or patients who present with advanced disease.

And in the 2000s and 2010s, the likelihood that someone was alive 24 months after diagnosis with recurrent or advanced-stage disease was about 30 percent, because not only did frontline paclitaxel and carboplatin not cure patients with recurrent or metastatic disease, but we also had nothing to treat them with in subsequent lines of therapy. We made things up, but the only thing we really had was the endocrine therapy progestin. And that's only for a subset of individual cancers that are driven by hormone receptors.

So that was the state of the world until 2023. We put into action finally the TCGA4 molecular subgroups, which are tumors that are POLE, tumors that are deficient mismatch repair or microsatellite unstable, tumors that are not mismatch repair deficient or mismatch repair proficient, and then tumors that are TP53. So these four subgroups. We finally, in following with our medical oncology colleagues and immune checkpoint inhibitors, brought those into the frontline metastatic setting in a number of big phase 3 global studies that enrolled all-comers but looked specifically at deficient mismatch repair tumors. And that was really the sea change for endometrial cancer because in deficient mismatch repair tumors, we saw what could be cures.

We haven't followed these patients long enough yet, which is an amazing thing to say because these studies were presented in 2023, and it's 2025, and we still have not seen final overall survival from these studies. So that already tells you that something has changed for patients with endometrial cancer in the past, we would have seen OS already.

ReachMD Announcer:
That was Dr. Kathleen Moore talking about the evolving landscape of endometrial cancer care. To access this and other episodes in our series, visit Project Oncology on ReachMD.com, where you can Be Part of the Knowledge. Thanks for listening!