8 reasons why ovarian cancer screening fails

Ovarian cancer is a nasty disease and the most lethal gynaecologic cancer. It affects 1300 women every year in Australia and the majority of these women will die of the disease.

Three out of four patients are diagnosed at stages 3 or 4 where the disease is widely spread and can be hardly controlled by treatments. The aim of ovarian cancer screening would be to shift cancers diagnosed at stages 3 or 4 towards stage 1 where treatments are more effective and survival would be much better.

Three very large research studies have been published to date and suggest that ovarian cancer screening should not be recommended. The largest study published this year involved 200,000 UK women.

These are the 8 reasons why major screening efforts for ovarian cancer screening fail.

1. The lack of a reliable test. The tumour marker CA125 is a protein secreted from cells of the abdomen, the chest and the heart. CA125 can be measured though a blood test but any process in abdomen, chest or heart, benign or malignant, will elevate the CA125 blood test reading (false positive test). Conversely, not all ovarian cancer types cause elevations in CA125 and we estimate that 10% to 20% of all ovarian cancer escape this test (false negative test). Transvaginal ultrasound was promoted to diagnose ovarian cancer for many years. Well-designed research studies have demonstrated that some ovarian cancers are so small so that they are not visible on ultrasound (false negative). On the contrary, some benign tumours alert doctors through ultrasound and lead to unnecessary surgery (false positive).  We simply need more specific and more reliable tests than the ones that are available at present.
2. CA125 and ultrasound tests can even cause harm if interpreted incorrectly. For example, a patient attends a well-women-check and her doctor finds a suspicious tumour on ultrasound. This patients CA125 reading is also elevated and the patient will be recommended to have explorative surgery. Overall, her risk of a surgical complication is 7%. Therefore, we accept that these tests result in unnecessary surgery and possibly in unwanted surgical outcomes.  
3. Too uncommon. Ovarian cancer is deadly but the lifetime risk of a woman in Australia is only 1.3%. For statistical reasons the intervention to screen for an uncommon disease needs to have a very large effect compared to a common disease.
4. In the past, women who were offered screening included women at the average1.3% risk to develop ovarian cancer during their life time. With BRCA andLynch testing becoming very affordable (the cost is as low as $400 in August 2016) a lot more women will have BRCA and Lynch testing. I suggest that women with BRCA or Lynch should be invited to screening trials rather than women at low risk.
5. The natural biology of ovarian cancer is poorly understood.  We don’t know what causes ovarian cancer and we also don’t understand the steps towards development of ovarian cancer. Emerging research suggests that the origin of some types of ovarian cancer is in the Fallopian tube rather than in the ovary. We also need to understand and identify the early stages of ovarian cancer. Once we are able to identify those, “early” interventions would likely be successful to prevent the disease in the first instance.
6. The regular PAP smear will not detect ovarian cancer. The PAP smear collects cells from the outside of the female genital organs, whereas the ovaries rest deeply inside the pelvis.
7. Lack of early symptoms. Ovarian cancer patients develop symptoms, such as urinary frequency, fullness, increase in abdominal girth or changes in bowel habits. Unfortunately, these symptoms reflect late stage disease. No “early” symptoms are known.
8. Lack of research funding and culture. As a gynaecological cancer specialist and researcher I can assure you that government funding for research has dramatically decreased in the last few years. Small and medium sized research projects can still be funded but big projects that require large amounts of funding are virtually impossible to do. Big research funding has largely stalled.

The burden of ovarian cancer is estimated to be an unbelievable 15,000 Quality of Life Years every year. To minimise this number, we need to invest into short-term and long-term research strategies.

In the short term research into the effectiveness of salpingectomy (removal of fallopian tubes) to reduce the incidence of ovarian cancer would most likely be effective. Women at high risk of developing ovarian cancer should have a salpingectomy instead of a tubal ligation and women who have a hysterectomy should have the fallopian tubes removed. These things are easy to do and inexpensive.

To achieve long term outcomes, lab-based researchers need to collaborate with clinicians and other experts to develop molecular treatments for this nasty disease. This can involve the development of novel molecules that identify cancer cells and allow making these cells visible for diagnosis. This can also mean that these molecules introduce anti-cancer agents that can destroy those cells.