An experiment in earlier detection of ovarian cancer

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For years medical students had it drummed into their heads in class, and the message was passed on to doctors in training by their teachers and their textbooks: ovarian cancer has no symptoms. The problem with the received wisdom is that it is wrong. Far from its historic portrayal as a silent killer, ovarian cancer is preceded by symptoms, as recent evidence shows.

Women who are ultimately diagnosed with the disease, and usually at a late stage, say that they did have symptoms, primarily gastrointestinal or urinary, for 3 to 4 months on average before diagnosis.

Because of these delays in diagnosis, patient groups have pressed for education about early symptoms among women and doctors. Last week, several US organisations, including the Gynecologic Cancer Foundation, the Society of Gynecologic Oncologists, and the American Cancer Society, released a consensus statement on the symptoms of ovarian cancer. The statement urges women to seek medical attention if they have new and persistent symptoms of bloating, pelvic or abdominal pain, difficulty eating or early satiety, and urinary urgency or frequency.

The case for a new approach to ovarian cancer diagnosis rests on dismal statistics. In the USA, ovarian cancer is the most common cause of death from a gynaecologic cancer, and the fifth most common cause of cancer deaths among women. Women with a family history of ovarian cancer, and those who carry mutations in the BRCA1 or BRCA2 genes, are at increased risk of the disease. About 22 000 US women will be diagnosed with ovarian cancer this year, and 15 000 deaths are predicted. The overall 5-year survival rate is 55%. But if the cancer is detected before it has spread beyond the ovary, the 5-year survival rate rises to 93%. If the diagnosis comes at a late stage (stage III or IV), however, as happens in 80% of all women with ovarian cancer, the survival rate is only about 30%.

Screening for the disease is difficult. The available screening tools, cancer antigen 125 and transvaginal ultrasound, have not been shown to be sensitive and specific enough to recommend them for the general population. No major medical organisation recommends routine screening in asymptomatic women. However, a UK pilot study, published in The Lancet in 1999, showed a survival benefit for screening using these two modalities. Final results will be reported in 2012. The hunt for specific biomarkers is on, but success is probably years away.

Because of the current limitations of screening, researchers have turned to specific symptoms as a potential method to identify the disease at an earlier stage. Studies of symptoms have confirmed that women with ovarian cancer have gastrointestinal, abdominal, and urinary symptoms. Such symptoms are, of course, often vague and associated with many other diseases and conditions, and for every ovarian cancer detected, many false positives might also result. But, according to a paper published in Cancer in 2007, ovarian cancer symptoms are more recent and greater in severity and frequency in women with the disease than in those without.

Given how relatively common and diffuse the identified symptoms are, will the consensus statement be of any use? The answer to that is likely to be mixed. On the one hand, anything that leads to greater awareness of the disease among women and puts ovarian cancer on the differential diagnosis list when women see their doctors with these complaints is commendable. On the other hand, the statement provides no specific guidance for doctors about what to do when such women present to them; the need for the challenging art of clinical judgment remains acute. Attention to early symptoms as recommended will certainly identify women who do not have ovarian cancer, and unnecessary, potentially harmful testing and procedures will result. There is no evidence whatever that detection based on these factors will substantially shift diagnosis early enough to affect mortality.

Despite these considerable limitations, the statement is a move in the right direction. Its chief contribution might be to improve communication between women and their doctors. To maximise its chance of success, the release of the statement should be combined with other efforts, especially increased funding for ovarian cancer research, which has been declining for the past several years; large prospective trials of early detection methods; ongoing education and awareness campaigns for the public and professionals; and development of standardised diagnostic algorithms for the disease.

The Lancet

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