Heterogeneity of Endometrial Cancer

Brad Monk, MD, FACOG, FACS: Hello, and welcome to this OncLive® Peer Exchange® entitled, “Evolving Treatment Paradigms in Endometrial Cancer.” My name is Brad Monk. Greetings from Scottsdale, Arizona. As you know, I work for US Oncology, Inc, here in Phoenix. I’m also a professor at Creighton University and the University of Arizona, also here in Phoenix.

Joining me today are 4 experts and friends. I am going to start with Nicoletta Colombo from Milan, Italy, at the European Institute of Oncology [Istituto Europeo di Oncologia]. Nicoletta, hi. Thank you. We are going to call each other by our first names; we are friends and colleagues. I am so thankful that they are here.

Next is Vicky Makker from the Memorial Sloan Kettering Cancer Center in New York. Vicky, hi. Also joining us is Domenica, who I know as Ketta Lorusso, from one of my favorite cities. Sorry, Nicoletta, I love Milan, too and New York—but Rome, Italy. Ketta, thank you for being with us.

Domenica (Ketta) Lorusso, MD, PhD: Hi. Thank you.

Brad Monk, MD, FACOG, FACS: Also here is Dave O’Malley from The Ohio State University. Welcome, Dave.

David O’Malley, MD: Thank you. I am very upset that you do not find Columbus, Ohio, to be one of your favorite cities.

Brad Monk, MD, FACOG, FACS: Well, it is—I’ve got no comment for that. Today, we will review current treatment options as well as emerging new strategies for the treatment of advanced and recurrent endometrial cancer, including exciting new data from the 2021 Society of Gynecologic Oncology [SGO] conference. Let’s get started. I was asked once if there was 1 word to describe endometrial cancer, what would that word be? That word is heterogeneous. It is so true; it is a constellation of diseases. Ketta, why don’t you kick us off and tell us what that means to you—the heterogeneity of endometrial cancer?

Domenica (Ketta) Lorusso, MD, PhD: For sure. For several years, we believed that endometrial cancer was a single disease. Then we discovered that there were at least 2 tumors, endometrioid and nonendometrioid tumors. Actually, the molecular classification of endometrial cancer reported that there were at least 4 different tumors with clearly different prognoses. This molecular feature may have clinical and therapeutic implications. The guidelines report that endometrial cancer should be profiled according to the molecular features because this has a clear impact on prognosis but also on treatment. We discovered 4 tumors—4 different tumors—in endometrial cancer.

The type with the worst prognosis is the TP53 mutation, for which chemotherapy is necessary, andchemotherapy is likely not enough. On the opposite end of the spectrum, we have the POLE-mutated tumor, which represents the best prognosis. For this tumor, it is possible that no kind of treatment is necessary. Then we have the 2 groups with intermediate prognosis: the MSI-high [microsatellite instability-high] or MMRd [mismatch repair deficient] tumors. These unstable tumors that have an intermediate prognosis do not seem to respond so well to chemotherapy. For these tumors, immunotherapy possibly represents the new standard in the future. Then there is the NSMP [nonspecific molecular profile] tumor, which has no specific molecular profile. This tumor has an intermediate prognosis, as it does not respond so well to chemotherapy; still, these tumors can respond to chemotherapy, but this tumor should probably be treated in the future with hormonal treatments. It is a very different scenario.

Brad Monk, MD, FACOG, FACS: I love that. Dave, do you talk that way? Do you say, “Oh, this is a p53-mutated endometrial cancer,” or do you still use “serous” and “endometrioid?” An endometrioid tumor, just as she says, could be MSI-high. It could be hormonally driven or p53-mutated, so the “endometrioid” term really isn’t helpful. Do you use that terminology, or is it still evolving?

David O’Malley, MD: I think it is really still evolving. We are challenged in getting our pathology colleagues on board in regard to some of this molecular testing at the local institutional level. We need to start talking about the molecular signature rather than the histology.

Transcript Edited for Clarity