Ovarian cancer screening with simple blood test

MD Anderson Cancer Center
Date: 09-09-2013

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Lisa Garvin: Welcome to Cancer Newline, a podcast series from the University of Texas and the Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment and prevention, providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin and today, our guest is Dr. Karen Lu. She is the Chair of the Gynecologic Oncology and Reproductive Medicine Department here at MD Anderson, here with some exciting news about a study on CA 125, which is a biomarker for ovarian cancer. Welcome, Dr. Lu.

Dr. Karen Lu: Thank you so much, Lisa.

Lisa Garvin: Let's talk about this. CA 125, this is part of an ongoing study, but you have updated findings, so what are you finding?

Dr. Karen Lu: So, CA-125 is an old marker. It's been around for a long time and we use it when we care for ovarian cancer patients as a way to monitor their disease. But there has always been the hope that perhaps we could use it for screening for women in the general population to detect ovarian cancer at an earlier stage.

Lisa Garvin: Tell me about when the study started. This is about an 11 year old study, correct?

Dr. Karen Lu: Exactly. This study is part of a -- our specialized Program of Research Excellence grant from the National Cancer Institute. And, we've really been focused on coming up with a strategy for early detection of ovarian cancer. We know that if we can identify ovarian cancer at its earliest stages, our cure rates can be as high as 90%. But, in over 75% of women with ovarian cancer, it's caught at later stages when our cure rates are not as high. So, this study has been ongoing and we're really testing a two-stage strategy in which the first stage is to do a simple blood test, CA 125 and to look at it over time. So each woman, essentially, develops their own baseline. And when we see that there's a change over that baseline, that will trigger us to do the second stage which is an ultrasound. So, in our study, we found that the vast majority of women just had to come back on an annual basis. Very small percentage, about 6% of them, had a slight increase in their CA 125 at some point and so we had them come back at three months to get another data point. And finally, less than 1% of the time, over this 11 year period, did we actually have to get an ultrasound.

Lisa Garvin: And this was over 4,000 women at several different sites, correct?

Dr. Karen Lu: Correct. It was over -- It was held, the study is ongoing in multiple sites throughout the United States.

Lisa Garvin: Well, let's talk about CA 125 and biomarkers. What is a biomarker exactly?

Dr. Karen Lu: Well, in this case, it's a simple blood test and essentially, the tumor secretes this antigen and it's measured and, like I said before, it's a biomarker that's been around for a long time and we use it for the care of ovarian cancer patients. And one of the things that's important to know is that there have been large studies that have shown that when you look at it at a single time point, it's not effective as an early diagnostic tool. So, we're really looking at it in a new way, where we're looking at the change over time.

Lisa Garvin: So that would be similar to the prostate-specific antigen test. Correct? Do they not set a baseline for men with prostate cancer?

Dr. Karen Lu: It's similar. It's similar in that what we're saying is that each individual is different. Someone may have a higher number, but their baseline stays at that higher value. Whereas, other women may have a lower value and it stay at that point. So each woman essentially becomes their own control.

Lisa Garvin: And I know that's something that's been needed for ovarian cancer for a long time, an early screening tool. I mean, we used to call ovarian cancer the silent killer. Is that still true to an extent?

Dr. Karen Lu: It is. It is. There certainly have been studies that have talked to women with ovarian cancer and those women have told us that they have had symptoms but they've been very non-specific, bloating, you know, increase in the size of their abdomen, difficulty with their bowel habits or their bladder habits. So they're non-specific so that when they go to talk to their doctor about these symptoms, their doctor, oftentimes, will say to them, oh, it's just menopause or, you know, we think it's inflammatory bowel symptoms and so that's why ovarian cancer, the diagnosis can often be delayed.

Lisa Garvin: But I think some women, including myself have been getting CA 125 tests at their doctor for the past three or four years. What was going on there? Was it being used as a screening tool in clinics?

Dr. Karen Lu: Well, it really shouldn't. And I would encourage women not to have it done. Right now, we know -- we have -- this study shows that there is some compelling data to suggest that this strategy, this two-stage strategy should work. The fantastic part is that there is a companion, similar study going on in the United Kingdom. We had 4,000 women in our study. This study is 200,000 women. It's a huge study that is powered to determine if this strategy will decrease mortality from ovarian cancer and that is the gold standard that we use for screenings tests. So they've actually completed all of their screening and they're just waiting to see survival over time and so, in 2015 we should have an answer to whether this screening strategy is going to be effective for women who are post-menopausal. So that's exciting. Our study gives us a little bit of insight into the early cases that can be picked up and that was the really striking thing about our study is that we picked up cancers in women who had been in the study for several years who had not -- who had very normal, low CA 125s and then we actually saw the CA 125s rise. We identified -- you know, they were triaged to an ultrasound. They had abnormal findings. They went to surgery and in all four cases, these individuals were identified with early stage ovarian cancer and that's in contrast, again, the 75% of women who were diagnosed with late stage ovarian cancer.

Lisa Garvin: And I think the evolution of CA 125 is interesting because, and this I did not know, that it was discovered actually 30 years ago by someone who is now a professor at MD Anderson.

Dr. Karen Lu: That's right. It was discovered by Dr. Robert Bast and he was at Dana-Farber at the time, but it's -- the marker itself is not new. And I think that's one of the things that we've learned as well is that, you know, we can't put all of our eggs in finding that perfect marker out there. It may be that there's no single marker that's a perfect marker. We've got to take what we have, continue to do discovery because discovery is important, but also be smarter about how we apply those biomarkers for clinical use.

Lisa Garvin: And I think that's interesting that something that was discovered 30 years ago, I mean, it actually evolves over time. At first it may not seem so great, but upon further study, it actually is great.

Dr. Karen Lu: Absolutely. I think that's been one of the surprising things to me personally. You know, I know that when I started this study, we were also doing many other discovery, biomarker discovery experiments in the lab and I think that over time we've really realized that it's not -- it's not just a new marker that's going to be helpful for us, but, you know, kind of being smarter with what we have.

Lisa Garvin: Because you said at one point that you were hoping to find something better than CA 125, but actually, CA 125 kind of rose to the top of the crop anyway.

Dr. Karen Lu: Absolutely.

Lisa Garvin: So, those women who have received CA 125 tests through their clinician, you're saying now that they should probably not be doing that. Can you explain that?

Dr. Karen Lu: Sure. I'm talking about low-risk women, so women at general population risk. And I think that's important because women who are at high risk, women who have a BRCA1 or BRCA2 mutation or women who have a very strong family history, we have different recommendations for those women. But I'm talking about the vast majority of women who are over 50, post-menopausal. Right now there's no recommendation, and in fact, the U.S. Preventive Task Force is very clear that there's no screening for ovarian cancer that is effective.

Lisa Garvin: Now, how does -- would this evolve to the clinical setting where we would actually use this as a screening tool?

Dr. Karen Lu: Well, like I said before, it's important for us to wait for the results of the UK, the United Kingdom, ovarian cancer screening study. Once we get those results, I think that we can start to consider whether ovarian cancer screening using this two-stage approach is going to be useful for the general population.

Lisa Garvin: I think we found that a lot of cancer-screening tools are kind of imperfect and do generate false positives. How do you hope to address that?

Dr. Karen Lu: So that's very important for ovarian cancer because it's not a common cancer. There's another reason why it's very important to have a very high specificity or in layman's terms, very few false positives. If you think about breast cancer, if you have a screening tool that is imperfect, we do a biopsy to confirm the diagnosis. But for ovarian cancer, in order for us to confirm the diagnosis, we actually have to do a surgery that incurs risk as well. And so if we have a high false positive rate of our ovarian cancer screening strategy, we're going to put women through surgery's that may be unnecessary. So, one of the things that this study clearly demonstrated is that this two-stage strategy had a very low false positive rate.

Lisa Garvin: And this study has merit as part of MD Anderson's Moon Shot Program for ovarian cancer. Does it not?

Dr. Karen Lu: So the Moon Shot Program for women's cancer is very exciting. There are several different aspects to it. The idea is that we really want to accelerate our findings and really our impact for ovarian cancer patients. So that includes discoveries for screening, discoveries for treatment for ovarian cancer, women and surgical innovation as well.

Lisa Garvin: So in closing, Dr. Lu, what sort of encouragement or information should they take from this discovery?

Dr. Karen Lu: I think there should be cautionary optimism. This study was large. It was done over a long period of time and it really showed us one of the few rays of hope for ovarian cancer screening in the general population. But it's important not to make a change in terms of clinical management right now. And I'm really hopeful as well that we'll have an answer in the very near future about whether this strategy is effective.

Lisa Garvin: And what about women who are post-menopausal and over 50? What sort of things should they be doing or asking their doctor?

Dr. Karen Lu: One of the things that we tell women is to really pay attention to their bodies and if they have symptoms that are worrisome to them that last more than two weeks to not ignore them, to speak to their physicians and to have their physicians think about ovarian cancer as a possible diagnosis.

Lisa Garvin: Thank you, Dr. Lu, for being with us today. Information about this ongoing study is available in the September 2013 issue of Cancer. If you have questions about anything you've heard today on Cancer Newsline, contact Ask MD Anderson at 1-877-MDA-6789 or online at mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.

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