Beth Y. Karlan, MD: What’s New in Screening for Ovarian Cancer?
Beth Y. Karlan, MD gives an overview of what’s new in ovarian cancer screening at ASCO 2011. Beth Young Karlan, MD is Director of the Women’s Cancer Research Institute, the Division of Gynecologic Oncology in the Department of Obstetrics and Gynecology and the Gilda Radner Cancer Detection Program. Dr. Karlan is also a professor of obstetrics and gynecology at the David Geffen School of Medicine at the University of California, Los Angeles (UCLA).
The Group Room at the 2011 American Association For Cancer Research Annual Meeting was made possible, in part, by:
VIDEO TRANSCRIPT
Selma R. Schimmel, Founder & CEO, Vital Options International
This is Selma Schimmel at ASCO 2011 where we continue our discussion with physicians addressing a variety of cancer types and breaking news and new data. And now we’re going to talk about ovarian cancer with one of our nation’s leading authorities, Dr. Beth Karlan. Dr. Karlan is the Director of the Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sanai Medical Center in Los Angeles, California. She is also Professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California Los Angeles, UCLA. Hello, Dr. Karlan.
Beth Y. Karlan, MD, Dir. Women’s Cancers Research, Cedars-Sinai Medical Center, Los Angeles
Good to see you, Selma.
Selma R. Schimmel:
More on ovarian cancer- where are we with screening?
Beth Y. Karlan:
I think, for those of us who see ovarian cancer patients every day and have really invested our lives and our research into understanding and trying to make an impact on the disease, an effective screening test really has been our holy grail. We do a pretty good job when ovarian cancer is lucky enough to be found at stage 1 where we really can talk about cures and use that 4-letter word for over 90% of the women. So, we wouldn’t be having to talk about PARPs and other chemotherapy trials to look at just progression free survival if we can find a way to cure patients. So much of that will be surrounded in us being able to find the disease while it’s still confined to the ovaries, stage 1.
Beth Y. Karlan:
Reported here at this meeting were the results from the PLCO trial, which is the prostate, lung, colorectal and ovary cancer screening trial funded by the National Cancer Institute here in the US, and a very important trial in that it’s one of the first screening trials that is powered. It will enroll enough patients that we can have a mortality outcome. So it wasn’t just, were more cases found, but did it impact the overall mortality? Those patients who were screened, did they actually live longer than those that weren’t screened? So PLCO enrolled about 78,000 women between the ages of 55 and 74. The ovarian cancer arm that was presented here at ASCO focused on those women, so they were randomized into usual care, which is really no screening, because that is our standard currently, versus annual transvaginal ultrasound and annual CA125. And what was presented here was the overall survival and the morbidity and toxic data. In each arm of the trial there was no significant difference in the number of ovarian cancer cases found. So screening didn’t find more cases of ovarian cancer than the current usual care. There also was no down staging as a result of screening, there were just as many late stage cancers in the screened arm as there were in the unscreened arm. The biggest downer from the data was the fact that there was significant harm seen in the screened arm. There were over 1,000 false positive screens, either an ultrasound showing a cyst, was the most common one that led the patients to undergo surgery. And there were 166 patients who had significant surgical complications from the surgeries that were indicated because of the results of screening. And that gives us all a moment to pause. We want to find ovarian cancer early. And this was a general population risk- these were women who did not have a family history, and so there may have been even a downside to participating in the trial and having screening. Now, I think we need to keep this all in some perspective. There will be some good things that come out of this trial. Usha Menon, MD, from the UK, who discussed the trial did compare this trial to what is being done there – and those data won’t be available yet for a number of years – where they are looking at CA125 not just as a positive or negative result, but more as a dynamic variable in terms of the rates of change of CA125, and then using that as a trigger. So those data are still ongoing.
Selma R. Schimmel:
While this question may not relate to screening, per say, the HE4 test, how important is that now for the woman, who is already diagnosed or you’re undergoing surveillance, in combination with CA125? And also, is there an evolving role for PET technology?
Beth Y. Karlan:
HE4 is a complimentary tumor marker with CA125 and is being used in the setting of post treatment surveillance. For those women who have already achieved remission, adding HE4 to CA125 enhances our ability to find recurrent disease. We are currently conducting a clinical trial through our NCI-funded SPORE grant that we call the ‘novel markers trial’ that is randomizing patients to be screened with either CA125 alone or CA125 plus HE4 to see whether or not the addition of HE4, in the screening setting, will then trigger folks to go on to ultrasound and surgery for more appropriate causes. Data presented here at the meeting, looking at CA125 plus 4 other markers and constructing a composite algorithm and looking at the rate of change. And those data were then validated using a GOG set of stage 1 patients, and indeed a composite algorithm including HE4, CA125 and 3 other markers appeared to perform better than CA125 alone. We’re not quite there and I do – before I touch on PET technology that you asked – I do want to just say the PLCO trial did establish a very, very important resource for investigators. There’s a serum bank and every time women came in for participation in the trial, or not, we have a blood sample so that as we discover better markers we don’t need to do another large trial for 15 years, we have a bank of pre-diagnostic serum. So let’s say we have a patient, let’s say, who is diagnosed with ovarian cancer in year 6 of the trial, we have annual serum samples from her. So if we have a marker we can say, okay it went up a year before, 2 years before, and really have this resource that I think will really accelerate our ability to find a worthwhile screening modality. Because I do believe that that is in the near future. We are so committed to finding that that it is in the near future. I don’t think PET scans are going to be the answer. PET and PET-CT technology is very helpful, again, in the recurrent setting, and actually changes our planned therapy in about a third of cases where the addition of PET-CT might tell you someone should have surgery or shouldn’t have surgery when they have recurrent disease. In the screening setting, there is too many false positives along the way, it’s too costly, it really is best used with CT scans and the cumulative use of CT scans and the radiation associated with that might have too many deleterious effects for us to advocate that. But I do think as we understand more about ovarian cancer biology, the subgroups, as we now think of, type 1 ovarian cancers and type 2 ovarian cancers, we also can focus our screening efforts and resources to more appropriately focused- perhaps ultrasound will be better for type 1 tumors and biomarkers for type 2 tumors. So, I think the vast commitment of the medical scientific advocacy community and partners will advance our causes and our goals to really be able to detect ovarian cancer early and cure ovarian cancer no matter what stage at which it is diagnosed.
Selma R. Schimmel:
I really appreciate what you did, because you gave us a great comprehensive overview with these various, hopefully, from the screening, pre-cancer stage to women who are dealing with metastatic and recurrent disease.
Beth Y. Karlan:
Every day is a gift and we need to do our best to make the quality of every day the best for every person we interact with, especially women. Women with ovarian cancer continue to inspire me and enrich my life.
Selma R. Schimmel:
I’m one of those women and I’m one of the women that was a part of your early research. So sitting with you and seeing the research evolve, and having lost my mother and my grandmother to ovarian cancer, it’s inspiring just talking to you.
Beth Y. Karlan:
It’s mutual then.
Selma R. Schimmel:
Thank you, Dr. Beth Karlan; Director of the Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute at Cedars-Sanai Medical Center in our hometown of Los Angeles, California, Professor of Obstetrics and Gynecology at the David Geffen School of Medicine at the University of California Los Angeles.
Beth Y. Karlan:
Thank you so much, Selma.
Selma R. Schimmel:
Thanks, Dr. Karlan.
END OF VIDEO