Bradley J. Monk, MD, FACS, FACOG: I was asked the other day, “Brad, what’s the No. 1 word used to describe endometrial cancer?” One word. I said, “Heterogeneity.” It is a constellation of diseases. Brian, Dr Slomovitz, tell us a little about how we’re classifying these tumors at the molecular level.

Brian M. Slomovitz, MD: Sure. Thanks for that, Brad. Historically we’ve classified these primarily by traditional factors—histology and endometrioid being the most common—followed by serous and clear cell, which are some of the more aggressive histologic subtypes. We still classify them by stage and grade. But of all the cancers we’re treating, the molecular subtypes have really been well defined in endometrial cancer. Ever since Doug Levine published the first TCGA [The Cancer Genome Atlas] article on endometrial cancer, dividing endometrial into 4 distinct subtypes, we’ve really been able to define clear categories for disease and also come up with better treatment plans based on those categories.

Briefly, there’s MSI [microsatellite instability] high, and there’s the POLE mutations. The MSI high make up about 40% of endometrial cancers. POLE is in the single digits—not that common, with a good outcome. There’s the typical low copy number, we call them, endometrial cancers. Then finally, the most aggressive type, the type that are most likely to be ovarian cancers, the TP53 subtype. But they’re really well characterized. Not only can we easily divide the cancers into those groups, but those groups really are prognostic and can determine outcome.

Bradley J. Monk, MD, FACS, FACOG: It’s interesting. As gynecologic oncologists, we use the FIGO [International Federation of Gynecology and Obstetrics]staging system. We don’t use the TNM [tumor, nodes, metastases] system. Stage I is limited to the endometrium, stage II in the cervix, and stage III is in the nodes. But Katie, I’ve heard you talk about the molecular staging—maybe this is what Brian said—that there may be a molecular way to look at prognosis rather than disease spread. Tell us about that.

Kathleen N. Moore, MD: We still have work to do with that characterization. But certainly, alluding to what Dr Slomovitz just mentioned with the TCGA, there have been other interesting studies done in Europe that are consistent. When you look at endometrial cancers that have loss of TP53, which we are very used to seeing in ovarian cancer. But in endometrial cancer, we’ve known about it for a while. It’s mainly those patients with uterine papillary serous or very undifferentiated grade 3 endometrioid cancers can have this TP53 signature. They’re serous-like and they have a poor prognosis, even when you are controlling for stage.

A stage I, which is all confined to the uterus, endometrioid vs 1 of the loss of TP53 tumors, that latter tumor is going to have a much different prognosis if left untreated. How best to treat it—we’re going to talk about it in this session a little later. But we know that they’re much higher risk for recurrence. They make up a much higher percentage of those patients who present with advanced and recurrent disease, so are high unmet need. On the flip side, Dr Slomovitz also mentioned POLE. That’s an interesting group and we don’t understand it really well yet.

We have a sense that even though they are commonly found in undifferentiated tumors, they still have maybe a better prognosis. There’s been some retrospective looks that they do better than they should histopathologically. But it really hasn’t impacted how we treat them. More to come on that.

Bradley J. Monk, MD, FACS, FACOG: This is great.

Transcript Edited for Clarity