Scientists in the US suggest that current tests for diagnosing ovarian cancer are not good enough and we need to develop better ways of detecting the disease much earlier.

The study is published on 28 July in the open access journal Public Library of Science and is the work of researchers from Stanford University School of Medicine and the non-profit Canary Foundation, an organization dedicated to the early detection of many types of cancer.

The idea of ovarian cancer scares women and their doctors because it is so hard to detect in the early stages.

The National Cancer Institute (NCI) suggests that estimates show that 21,550 women will be diagnosed with ovarian cancer and 14,600 women will die of the disease in 2009. Worldwide, around 140,000 women die of ovarian cancer every year, wrote the authors.

And it is no comfort that recent studies suggest current tests produce many false positives and don’t make any difference to the rates of death.

The symptoms of ovarian cancer are vague and often don’t manifest until the tumor is already several centimeters in diameter, by which time it is probably already spreading to nearby tissue and organs.

That is why the overall five year survival rate is only 46 per cent (it is lower for more advanced stages), but according to the NCI, if diagnosis is made early, before the tumor has spread, the five year survival rate is nearer 93 per cent.

The authors of the PLoS paper said that to be able to make a significant reduction in the death rate of ovarian cancer, tests would have to be able to find tumors smaller than 1 cm in diameter, which is about 200 times smaller than the size currently used to assess new tests.

While this seems like an almost impossible goal, there is some good news: it takes around four years before cancers of this size become life threatening, so the window of opportunity for early life-saving diagnosis is quite large.

Stanford biochemistry professor Patrick O Brown, who co-authored the paper with colleague Dr Chana Palmer, of the Canary Foundation, told the press that:

“We are miles away from detecting the most deadly ovarian tumors at this early stage.”

“But now we have a chance of actually designing an effective test that will allow us to treat them before they become deadly,” he added.

Current tests for ovarian cancer look for abnormally high levels of protein in normal blood, but Brown suggested that blood tests would be more effective if they could rely on new markers that are never produced by small cells.

Another approach could be to use new molecular imaging techniques or use fluid samples from the uterus or vagina where tumors are likely to be more concentrated, he said, explaining that:

“Reliable early detection would save so many more lives than many new blockbuster anticancer drugs.”

“If we can do this, which is no small challenge, the potential to go from a less than 20 percent chance of surviving five years to a relatively minor surgery that would have a very high cure rate is huge,” he added.

The authors explained that part of the difficulty of creating a new reliable test is that there is more than one type of ovarian cancer.

The deadliest form, serous ovarian cancer, accounts for about half of all cases but is responsible for at least 80 per cent of the deaths because unlike other forms of the disease, serous ovarian cancer starts spreading to other sites when tumors are quite small and in most cases before diagnosis.

A flaw with the design of current tests is that they are based on the assumption, derived from observations of how other cancers progress, that early stage tumors are just smaller versions of late stage tumors.

However, Brown and Palmer suggest that in ovarian cancer the early stage tumors are intrinsically different from the ones that occur later and thus can’t be found using tests designed according to principles used in other cancer tests.

As Brown explained:

“It dawned on me at some point that we were being somewhat glib about what it was we were trying to detect.”

“What we really needed to know is what the more-dangerous tumors looked like before we knew they were there,” he added.

Brown and Palmer realized such a source of tumors could be tissue from women with the BRCA-1 gene mutation. Some women who know they carry this mutation elect to have their ovaries and fallopian tubes removed to reduce the risk.

Also, Brown and Palmer found when they analysed some previous studies, that although these women appeared healthy when they have the surgeries, in around 8 per cent of cases, closer examination of the tissue shows they actually had early undiagnosed serous ovarian tumors.

They then pooled the results of several studies and estimated the prevalence, location, size and stage of the tumors, and by comparing the results with the incidence of diagnosed serous ovarian tumors in a similar group of women, they estimated that the window of opportunity for early detection and potentially successful treatment to be 4.3 years.

They also suggest that for most of this time the tumors stay at less than 1 cm in diameter, but once they get to 3 cm, more than half of them are at stages III and IV (ie spread beyond the pelvis). Compare this to the 10 cm average diameter of an ovarian cancer tumor at time of diagnosis.

Brown said they found that most serous ovarian tumors that they reviewed had progressed to an advanced stage nearly a year before diagnosis.

He and Palmer estimate that to halve the deaths from serous ovarian cancer, we would need an annual screening test that could detect tumors at around 0.5 cm in diameter, which is far beyond the range of any of the currently available tests.

However, Brown said he was not gloomy about this. He is now trying to find out if there might be ovarian cancer markers in fluid samples taken from the vagina or cervix, which would overcome the problem of marker dilution that occurs with blood samples.

His great hope is that he will find a truly cancer-specific molecular marker, a new protein or piece of DNA that occurs only in ovarian cancer cells.

He thinks it may also be possible to devise ovarian cancer imaging techniques similar to the mammogram for breast cancer.

“The Preclinical Natural History of Serous Ovarian Cancer: Defining the Target for Early Detection.”
Patrick O Brown and Chana Palmer.
PLoS Medicine, PLoS Med 6(7): e1000114, Open Access, July 2009.
doi:10.1371/journal.pmed.1000114

Source: Stanford University Medical Center.

Written by: Catharine Paddock, PhD