Ovarian cancer is the most deadly of gynecologic tumors. For the past 25 years, scientists have tried to identify a screening test to detect ovarian cancer in its earliest stages, when the chance of cure is high. Unfortunately, multiple clinicaltrials with hundreds of thousands of participants have failed to identify an effective way to screen for ovarian cancer.
Fewer than 40% of those diagnosed with ovarian cancer are cured, and approximately 12,810 people in the U.S. die from the disease every year. In fact, the U.S. Preventive Services Task Force gave ovarian cancer screening a grade of D in 2018, meaning it recommends against periodic screening because it doesn’t improve survival and can prove harmful to patients.
Because no effective screening test currently exists, 70% of people with ovarian cancer are diagnosed at advanced stages, when chances of cure are poor. Around 60% to 90% of people with stage one or two cancer that stays around the ovaries and pelvis are disease-free five years after diagnosis, compared with only 10% to 40% of those with stage three or four cancer that has spread through the abdomen and beyond.
But even those with advanced disease have a higher chance of being cured if complete surgical removal is still possible. This makes early diagnosis all the more important for overall survival.
Without screening tests, many physicians wrongly assume that early diagnosis for ovarian cancer isn’t possible. As a gynecologic oncologist who treats hundreds of ovarian cancer patients each year, I was frustrated by these late diagnoses, and wondered if better recognition of its symptoms could help clinicians and patients identify ovarian cancer earlier.
Ovarian cancer has historically been called a “silent killer,” because clinicians thought its symptoms were undetectable. Patients were often diagnosed so late that doctors thought nothing could be done.
But there have been many studies over the past 20 years demonstrating that ovarian cancer does have early warning signs. My colleagues and I conducted one of the earliest studies in 2000. Our survey of 1,700 people with ovarian cancer found that 95% of patients reported noticeable symptoms three to 12 months before diagnosis. The most common symptoms were pain in their pelvis and abdomen, increased frequency and urge to urinate, difficulty eating or feeling full quickly, and bloating or abdominal distension.
Importantly, people with both advanced- and early-stage disease reported similar types of symptoms. Subsequent studies from multiple researchers further confirm that patients with even early-stage ovarian cancer experience frequent symptoms.
We also found that providers often misdiagnosed ovarian cancer as another condition. When we asked patients what their doctors told them was the cause of their symptoms, 15% had their symptoms attributed to irritable bowel disease, 12% to stress, 9% to gastritis, 6% to constipation, 6% to depression and 4% to some other cause. Thirty percent were given treatment for a different condition. And 13% were told there was nothing wrong.
One major issue has been distinguishing ovarian cancer symptoms from those of common gastrointestinal and urinary conditions. In another study, my team and I found that patients with ovarian cancer have symptoms with a recent onset and occur more than 50% of the month.
To facilitate early detection of ovarian cancer, my team and I compared the symptoms ovarian cancer patients experienced with those of patients without ovarian cancer. We developed an index that identified six important symptoms of ovarian cancer: bloating, increased abdominal size, feeling full quickly, difficulty eating, pelvic pain and abdominal pain. Symptoms needed to occur more than 12 times a month but to have lasted for less than a year.
Based on these criteria, our index was able to detect ovarian cancer in 60% to 85% of the patients in our study, a range similar to that achieved through diagnostic blood tests for ovarian cancer.
Preventing ovarian cancer
While early detection is important, there are also prevention strategies that can help reduce the risk of developing ovarian cancer.
If you have a family history of ovarian cancer, inform your doctor, who may recommend genetic testing to fully determine your risk, or prophylactic surgery to prevent the development of cancer.
Oral contraceptives, tubal ligation (or surgery to close the fallopian tubes), pregnancy and breastfeeding all reduce the risk of ovarian cancer.
Finally, up to 70% of ovarian cancers may arise from the fallopian tubes. Removing the fallopian tubes at the time of another surgery may be another option to help reduce the risk of ovarian cancer. This should be done only if you do not plan on becoming pregnant in the future.
Women with genes for endometriosis have higher risk of ovarian cancer
Researchers find odds of having ovarian cancer up to 2.6 times higher for women carrying genetic risk factors for endometriosis. These women also have a higher risk of developing certain ovarian cancers. A study of genetic markers in nearly 15,000 women with endometriosis and more than 25,000 women with ovarian cancer has found what researchers say is a causal link between the two conditions.
“We have estimated that the odds of having ovarian cancer over a lifetime is up to 2.6 times higher for women carrying genetic risk factors for endometriosis,” said the study’s lead author, Dr Sally Mortlock of the University of Queensland.
The genetic link was specific to certain kinds of epithelial ovarian cancer – the most common category, which accounts for an estimated 90% of cases.
Endometriosis – a condition in which the tissue similar to the lining of the uterus grows outside the uterus – affects an estimated one in 10 women of reproductive age.
“Endometriosis affects as many women as diabetes and asthma yet it has not received the same level of attention or funding, leaving women to suffer in silence,” Mortlock said. Mortlock emphasised that while there was a “significant overlap in genetic risk factors” between the two conditions, the overall risk for developing ovarian cancer was still low. She said having endometriosis increased the risk of developing ovarian cancer to one in 55, compared with an estimated ovarian cancer risk of one in 76 women generally.
“We explored specific areas of DNA that increase the risk of both diseases,” Mortlock said. The researchers found that women with 27 genetic markers – which have previously been strongly linked to endometriosis – were also more likely to have ovarian cancer. Using a statistical method known as Mendelian randomisation, the team were able to demonstrate a causal genetic link, and establish “directionality from endometriosis to EOC [epithelial ovarian cancer] risk rather than vice versa”.
“Some of these genes have important roles controlling the ability of our cells to adhere, or stick, to each other and respond to hormones,” Mortlock said. “This gives us clues that these pathways might be important in disease development and progression.” The identified genes could be used as future drug targets to treat both conditions, she said.
Tracy O’Mara, an associate professor at the QIMR Berghofer Medical Research Institute, who was not involved in the study, said the research demonstrated a causal relationship between the two conditions, which have previously been linked in epidemiological studies. “The relationship between endometriosis and ovarian cancer has [previously] been looked at observationally,” O’Mara said. “It’s nice that they’ve used these genetic techniques … it really shows the shared biology between the two.”
One limitation of the study is that its DNA data only included women of European ancestry. “Whether the results can be extrapolated to other ethnic groups is something that would need to be looked at as well,” O’Mara said. The research was published in the journal Cell Reports Medicine.
Chris Evert opens up about her stage 1C ovarian cancer diagnosis, saying she hopes her story will help other women watch for warning signs. Evert is undergoing chemotherapy, but says she knows how difficult the disease can be after watching her sister Jeannie die of the same cancer two years ago. NBC’s Anne Thompson reports for TODAY.
Encouraging trends abound in the management of ovarian cancer. As rates of ovarian disease continue to decline, there has also been a notable increase in tools for detecting it earlier in its course.
To better understand these developments, Medscape recently reached out to Rebecca Stone, MD, an ovarian cancer expert and associate professor of gynecologic oncology at Johns Hopkins University School of Medicine, in Baltimore, Maryland. This interview has been edited for length and clarity.
Medscape: There has been a decline in the rates of ovarian cancer in recent years. What are the possible causes of this?
Dr Stone: The number of new cases in the United States has actually been declining over the past two decades. This is thought to be attributable to the increased prescribing of oral contraceptive pills in the late 1990s and the uptake of preventive measures, such as risk-reducing gynecologic surgery for women with genetic predisposition to ovarian cancer, as well as opportunistic salpingectomy in the general population. Opportunistic salpingectomy was introduced about 10 years ago. It is a surgical means for primary prevention of tubo-ovarian cancer by removing both fallopian tubes at the time of elective surgery for women who have completed childbearing or in lieu of “tying the tubes” for women who desire permanent surgical sterility.
What can you tell us about a recent study suggesting that high-grade serous epithelial ovarian cancer may be detected earlier in the course of the disease by testing for TP53 clonal variants in DNA from Papanicolaou (Pap) tests performed during cervical cancer screening?
The idea here is that early mutational events that ultimately result in the development of epithelial ovarian cancer can be detected by performing gene sequencing on genetic material collected at the time of routine Pap smear screening done for cervical cancer. Pap tests are known to contain cells and genetic material shed from the fallopian tubes, where the precancerous lesions thought to give rise to epithelial ovarian cancer, predominantly serous epithelial ovarian cancers, start.
Researchers at the University of Turku have developed a test for ovarian cancer detection with a sensitivity 4.5 times higher than that of the conventional laboratory test. The simple lateral flow test is based on rapid detection of abnormal sugar structures directly from the blood sample.
The CA125 antigen, a plasma membrane glycoprotein found in the tissues of the female reproductive tract, is commonly used for the detection of ovarian cancer but works poorly on its own in identifying early stage cancers. The cancer specificity can be improved significantly when CA125 detection is combined with targeting aberrant sugar structures in the tumor.
The goal of the research group led by Professor Kim Pettersson at the University of Turku, Finland, is to develop novel tests that use the detection of modified sugar structures from the cancer tissue. The recently published article describes how the research group developed this rapid and sensitive point-of-care diagnostic test that can detect ovarian cancer from the patient’s blood sample.
Aberrant sugar structures can be used in early cancer diagnostics
With the easy-to-run and rapid test developed in the study, ovarian cancer can be more accurately detected from a blood sample in 30 minutes. The technologies of the Biotechnology unit at the Department of Biochemistry, as well as their expertise in label technology and rapid tests, were widely used in this study.
“When compared with the conventional CA125 diagnostics, the sensitivity of the new test was 4.5 times higher in detecting ovarian cancer,” says Doctoral Candidate Sherif Bayoumy, the first author of the study.
The aim is to expand further on these promising results to cover a larger group of patients and other cancers. The goal is to develop rapid tests for clinical use to facilitate to proceed to further examinations and treatment options.
“The received results are extremely promising for early cancer diagnostics. We are currently studying the functionality of similar approaches in other cancers. Detecting the disease as early as possible is extremely important when it comes to, for example, pancreatic cancer,” describes Professor Kim Pettersson.
Recent discoveries made by researchers at Texas A&M University could change the way ovarian cancer is understood and treated.
Dr. Abhishek Jain, assistant professor in the Department of Biomedical Engineering and the Department of Medical Physiology in the College of Medicine, collaborated with researchers from the Departments of Gynecologic Oncology and Cancer Biology at MD Anderson Cancer Center to gain a better understanding of the interaction among ovarian cancer tumors, blood vessels and platelets. They found that tumors break the blood vessel barriers so that they can communicate with the blood cells, such as platelets. When these tumors come into contact with platelets, they can then metastasize, or begin to spread to other sites in the body.
The collaborative research was recently published in the journal Blood Advances. Currently, researchers understand that platelets are one of the initiators of ovarian cancer metastasis but did not know what led to the introduction of the platelets to the tumor cells. Instead of struggling to view this relationship in animal models, Jain’s team brought a new solution to the table: organ-on-a-chip research.
Organs-on-a-chip are microfluidic medical devices the size of a USB drive. The team designed the OvCa-Chip to give researchers an easier window to view the biological processes between tumors and platelets.
In an interview with the International Society on Thrombosis and Hemostasis, Jain explained that “it basically is a microenvironment where ovarian tumor cells can be co-cultured along with their blood vessels, and then they can interact with blood cells. Once we learn about these interactions, we can then move forward to look into how drugs will impact these kinds of interactions.”
Viewing the interaction between tumors and blood vessels on the OvCa-Chip led the researchers to an extraordinary result — the tumor cells systematically broke down the endothelial cells, which are the barrier that lines the interior surface of blood vessels and prevents exterior interaction with blood cells. Once this barrier was gone, blood cells and platelets entered the tumor microenvironment and could be recruited for metastasis.
Harnessing this knowledge could change how clinicians approach ovarian cancer treatment, Jain said, suggesting that anti-vascular drugs could be considered along with anticancer treatments. A benefit of the organ-on-a-chip is that it can also test these novel drug treatments and drug combinations. Another application of the chips could be diagnostics.
“You have to understand that these are chips that are living. They contain living cells. The advantage is that these are all actually human samples. So what we think the future for this technology is, is perhaps we can advance it in the direction of personalized medicine where we could actually take stem cells from patients and other patient-derived cells and make this entire chip from a single patient.” Dr. Abhishek Jain, assistant professor in the Department of Biomedical Engineering and the Department of Medical Physiology in the College of Medicine.