Ovarian cancer is very hard to diagnose early. The disease rarely has easily noticeable symptoms in the beginning, and there is no effective way to screen for it. Because of this, most women with ovarian cancer are diagnosed and treated after it has spread elsewhere within the pelvis and abdomen. At that point, surgery and chemotherapy are less effective.
But there is reason to hope that researchers may have identified a strategy to overcome this hurdle. Evidence now suggests that the most common type of ovarian cancer usually starts as precancerous lesions in the fallopian tubes, the narrow tunnels through which eggs travel from the ovaries to the uterus.
MSK gynecologic oncologist and surgeon Kara Long Roche explains how this finding could radically improve early detection and treatment for women with ovarian cancer.
What made researchers suspect that ovarian cancer starts in the fallopian tubes?
Within the past decade, a growing number of women with high-risk mutations for ovarian cancer, such as BRCA1 and BRCA2, have opted for preventive surgery. The procedure, called a salpingo-oophorectomy, removes the ovaries and fallopian tubes. When pathologists studied the tissue, they found abnormal cells in the fallopian tubes, which they called serous tubal intraepithelial carcinomas (STICs). That led to the theory that these abnormal cells in the fallopian tubes could be the source of some ovarian cancers. But we needed more evidence.
How was a solid link made between STICs and ovarian cancer?
Pathologists can now use sophisticated tools, such as genomic sequencing, to analyze STIC cells. They have found that the cells share a lot of molecular and genetic characteristics with the most common form of ovarian cancer, called high-grade serous carcinoma. This type accounts for approximately 75% of ovarian cancers. A study published in November 2017 bolstered these findings. It used a mathematical model to estimate the average time between the development of STIC lesions and the onset of ovarian cancer. It came to about six and a half years. That’s a big window for possible intervention.
How could these lesions in the fallopian tubes be detected before they become cancerous?
Currently, it is impossible to biopsy fallopian tubes without taking them out. We are not able to do a screening similar to a colonoscopy, which involves inserting a camera into the colon to look for polyps before they become colorectal cancer. The fallopian tubes are very small, and the STIC lesions are microscopic in size. They can be detected only by pathologists examining tissue outside the body.
We’re trying to think outside the box for ways to access and analyze these cells. We are collaborating with Douglas Levine [a former MSK gynecologic oncologist who is now a part of NYU Langone Health] on an investigation into whether we can detect proteins or DNA fragments from these fallopian tube lesions in the blood or other body fluids. We are doing what is called uterine washing, where we use tiny tubes to inject saline fluid into the uterus. We collect the uterine fluid and look for these tissue-based biomarkers as early indicators of ovarian cancer. This research is still at an early stage, but we hope it can translate into clinical use.
How could early detection of these abnormal cells change treatment in women with a high risk of ovarian cancer?
It brings up a vital question: If we think ovarian cancer starts in the fallopian tubes, could we remove them as a preventive step? The only role the tubes play is to allow for spontaneous, natural, conception. They aren’t needed if you are using assisted reproductive technology, and they are not necessary to carry a pregnancy or to maintain normal hormonal status. For women with inherited BRCA1 or BRCA2 mutations, as well as a few others linked to a higher risk of ovarian cancer, we are investigating fallopian tube removal as an interim step before the eventual removal of the ovaries.
There is a lot of potential upside in removing only the fallopian tubes while leaving the ovaries intact. The procedure is straightforward, like having the tubes tied. It may offer protection against ovarian cancer without taking away a woman’s fertility or inducing early menopause, which are side effects of ovary removal. Research suggests that premature menopause might increase the risk of heart disease and other illnesses.
MSK is part of an ongoing clinical trial called Women Choosing Surgical Prevention. This study looks at how quality of life is affected when the fallopian tubes are removed first compared with the standard removal of fallopian tubes and ovaries at the same time. Is there actually a benefit? We think there is, but it needs to be validated.
What needs to happen before fallopian tube removal becomes a standard option for women to prevent ovarian cancer?
We need to better understand the process of ovarian cancer development. More evidence is needed on the protective effects of fallopian tube removal. If we can develop a way to reliably detect the precancerous cells, that would help women and their doctors make decisions about the best preventive approach. And most importantly, we need to do a better job of identifying high-risk woman with a genetic predisposition for this disease. We could prevent thousands of cases of ovarian cancer with counseling, giving women the option of risk-reducing procedures, and by making those procedures better.