NEW YORK (GenomeWeb) – Studies from US and UK researchers have found that diagnostics firm Abcodia's ROCA ovarian cancer test could be useful for monitoring patients at high-risk of developing the disease.
The studies, one led by a US-based group and published in Clinical Cancer Research in January, and the other led by UK researchers and published in the Journal of Clinical Oncology in February, found that monitoring with the ROCA test could help detect ovarian cancers early in high-risk women who choose not to undergo recommended ovary removal, or risk-reducing salpingo oophorectomy (RRSO).
Steven Skates, an associate professor at Harvard Medical School as well as first author on the CCR paper and one of the developers of the ROCA test, said that he and his colleagues now hope to combine data from the two studies to examine the test's utility "in greater detail and with more power."
He noted that work is ongoing to demonstrate the test's ability to detect ovarian cancer and reduce mortality in the general population.
Developed by Skates and University of New South Wales researcher Ian Jacobs, the ROCA test uses longitudinal measurements of the ovarian cancer protein marker CA125 combined with transvaginal ultrasound to enable early detection of the disease.
While CA125 has proven a poor ovarian cancer biomarker to date, the ROCA test aims to improve its performance by repeating CA125 measurements over a series of years, allowing patients to serve as their own controls. Women are given an initial CA125 measurement, and based upon that are assigned different levels of follow up. In the case of a low-risk score, patients are instructed to come back for an additional CA125 measurement in a year; in the case of an intermediate-risk score, they are instructed to come back for an additional measurement in three months; and, in the case of a high-risk score, they are given a transvaginal ultrasound and referred to a gynecological oncologist.
The longitudinal measurements allow patients to serve as their baselines, the idea being that this can allow doctors to detect small but significant changes that might be missed comparing the marker against population-based cut-off scores.
The ROCA test has shown promise in some studies, including a 2013 Cancer study by MD Anderson Cancer Center researchers that found it could identify cases of ovarian cancer with 99.9 percent specificity and a positive predictive value of 40 percent in a cohort of 4,051 women followed over 11 years. A 2015 study published in JCO by a team led by Skates and Jacobs, who is a non-executive director at Abcodia, detected 86 percent of ovarian cancers with specificity of 99.8 percent in a cohort of 46,237 post-menopausal women age 50 years or older from the United Kingdom Collaborative Trial of Ovarian Cancer Screening (UKCTOCS).
However, some parties, including the US Food & Drug Administration have argued that the test still does not have data supporting its use either for monitoring high-risk patients or the general population. In September 2016, the FDA issued a communication that recommended against using blood-based ovarian cancer screening tests, and the ROCA test specifically.
Abcodia had launched the test in a limited release in the US and UK in 2015, but suspended sales in the US and limited them in the UK in response to the FDA letter.
Speaking this week, Skates said that the UKCTOCS study had found solid evidence that the ROCA test could help shift the stage at which ovarian cancers are discovered to earlier. But, he noted, whether this would result in improved mortality results was not yet known. The UKCTOCS researchers are currently conducting additional follow up on patients to assess what, if any, reduction in ovarian cancer deaths resulted from using the test, and these results are expected in 2019.
In the general post-menopausal population, the test has shown a positive predictive value of around 25 percent, meaning, Skates said, that for every four surgeries done based on the test, one will find ovarian cancer. He added, though, that of the remaining three surgeries, two of the three identified a different issue, such as a benign ovarian neoplasm, or metastases from another cancer, for which surgery would be indicated.
In addition to the possibility of unnecessary surgeries, Skates noted that there are perhaps smaller but still notable downsides, such as having to undergo transvaginal ultrasounds and the anxiety induced by, for instance, an elevated but ultimately insignificant CA125 score.
"That's the sort of the breakdown, the trade-off you've got to make," he said. "For earlier stage detection without a proven survival benefit, is that worth it?"
If, though, the researchers are able to demonstrate a reduction in mortality, "the debate swings," Skates said. "It's a little more clear."
"I think there's a reasonable rationale for the general population screening, but I can also see people arguing against it, and with good rationale," he said. "Until this three-year follow-up is completed, we certainly won't have any consensus and we won't have an unequivocal answer there in terms of what is the impact."
In the case of testing patients at high risk of the disease, such as women with BRCA1 and BRCA2 mutations or Lynch syndrome, the consideration is not unnecessary surgeries, but, rather, giving patients a false sense of security that might prevent them from undergoing RRSO, which is typically recommended for such women.
Because RRSO essentially brings about immediate menopause, some women at high risk of ovarian cancer may wish, against medical advice, to avoid or postpone surgery, and there is concern that availability of a test like ROCA might encourage them to do so.
The FDA letter addressed this issue directly, noting that high-risk "women and their doctors may not take appropriate actions to reduce their future risk if they rely on a result that shows no cancer currently present."
Skates said he and his colleagues were "certainly cognizant of that potential effect," and that they noted throughout the CCR paper that the ROCA test is not intended for monitoring high-risk women but only that it could be useful for women who decide against medical advice to not undergo RRSO.
"It's impossible to guard against that, but our hope is to have a measured-enough tone in our conclusions that it wouldn't influence the decision in a positive way to put off surgery any longer than what they would have without this [test] being available," he said.
In any case, Skates said additional studies are needed to establish the test's utility in this setting. The UK-based study published in JCO was large enough to conclude that the ROCA test could help detect ovarian cancer earlier in women at hig -risk who decline, against current medical guidelines, to undergo RRSO, though it did not reach any conclusions about whether this earlier detection would lead to reduced mortality, Skates said.
The trials detailed in the CCR paper came to less firm conclusions, but, he said, gave "encouraging enough results to warrant evaluation in larger cohorts."