Transcript: Kathleen Moore, MD: There are various types of ovarian cancer. When you talk about ovarian cancer in general, we’re talking about the most common types, which are epithelial ovarian cancers. And there are a number of subtypes, which I’ll mention, but then there are some rare but still-important types of ovarian cancer. There’s a group called stromal tumors, or sex cord-stromal tumors. Those include tumors such as granulosis L or circular lighted tumors. And then there are germ cell tumors, which have different subtypes as well. And those are very important, rare, and treated very differently from the more common epithelial tumor. So that’s mostly what we’re talking about today: epithelial tumors.

So epithelial tumors are then subdivided further into the most common type, which is serous—or sometimes people will call them papillary serous—carcinomas. Those are the most common type. Then you’ll have endometrioid ovarian cancer, which is categorized as either high or low grade. And then we have clear cell, which is very rare and mucinous. And then there’s a subtype of serous ovarian cancer called low grade, which is a very different molecular tumor as well but still under the heading of epithelial ovarian cancer. So there are a number of subtypes under epithelial, which is the most common.

Knowledge of the type of ovarian cancer, the broad type and then the subtype, is actually becoming increasingly important. In the past, we did clinical trials and we did treatments just based on ovarian cancer. So if you had epithelial ovarian cancer, it didn’t matter what subtype, you treated them all the same. And to some extent that’s still a little bit true. We use a backbone of paclitaxel and carboplatin.

But we increasingly understand that those different subtypes or histologic subtypes, especially as they pertain to clear cell and mucinous and low-grade serous cancers, have very different molecular alterations that may respond to different therapeutics and different targeted strategies. So we are starting to individualize our clinical trials to certain types of histologic subtypes because we think they really do have potentially different responses to drugs and different prognoses.

When you talk about high-grade serous and high-grade endometrioid, which we tend to group together, they have very similar molecular profiles and prognostic profiles. Just like most ovarian cancer, they’re caught at a late stage. They are not likely curable, but their prognosis—meaning how long do patients live—is, in my opinion, quite good. It’s not long enough; it’s never long enough till we cure patients, but it can be years. So the median is right around 5 years, and sometimes much longer for certain subtypes.

Whereas if you look at clear-cell cancers, it’s somewhat less. Those tumors can respond to chemotherapy, but their responses overall tend to be less robust, and a lower percentage respond as well as the high-grade serous. And when they recur, there are less effective therapies. Mucinous cancers are very recalcitrant to the chemotherapies that we have and are a big challenge for us. And so those specific subtypes can have poor prognoses, and so we have a lot of work to do there.

Low-grade serous ovarian cancer is a very rare subtype. You often see it in younger patients. And so you can actually see long overall survival. So their prognosis again can be relatively good, but again, these tumors tend to not respond as well to chemotherapy, so they recur and we have this long line of therapies that women are on, sometimes for many years. So they tend to live about as long as their high-grade counterparts, maybe a little bit longer. But again, we have, I think, work to do there.

Michael Birrer, MD: The stage of diagnosis for ovarian cancer is very important for prognosis. As you know, 75% of ovarian cancers present with advanced-stage disease, stage III and IV; 25% with tumors that are essentially localized to the ovary or in the pelvis. Those tumors, that would be stage I and II, actually do quite well. So our 5-year survival might be anywhere between 85% and 90%. Compare that with stage III and IV tumors, where the 5-year survival may be 30% to 40%. And of course we have late recurrences, unfortunately. So if you want to look at overall survival, I’m a believer that we probably cure only 15% to 20% of advanced-stage ovarian cancers. We do much better with early stage. The cure rate is probably between 80% and 90%.

Progression-free survival for ovarian cancer is a little trickier because it depends on how you’re describing it. Certainly for advanced stage, stage III and IV, the progression-free survival after the initial surgery and chemotherapy is going to be between 12 and 20 months. That depends a lot upon the amount of tumor that’s left after surgery, because that’s a poor prognostic feature. And then, too, the recent exploration and validation of the value of maintenance therapy, which I think we’ll get into later on, has actually extended that progression-free survival remarkably, even after the first chemotherapy: up to 30 or 40 months.

Transcript Edited for Clarity