ROCA Test for early detection of ovarian cancer rolled out in U.K and 5 US states, sparks concern!

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The results of  UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS)  was published in  the online edition of  The Lancet on  December 17, 2015.

                                  

The trial was conducted by Professor Ian Jacobs, who’s now based at the University of New South Wales Australia, and Professor Usha Menon from University College London, both of whom are gynecologists and have been working on early diagnosis of ovarian cancer since very long.

The trial data does show that annual screening by CA125 does detect cancer at an early stage and the risk of death due to ovarian cancer was reduced by 20% in women screened. Based on this the researcher estimated  that  for every 10,000 women screened every year with a blood test, about 15 lives could be saved, assuming the  women were screened for 7 to 11 years.

The researcher themselves say that “Further follow up to assess mortality reduction is required before firm conclusions can be reached”.

On the basis of the preliminary findings Cancer biomarker pioneer Abcodia Ltd, based in the Cambridge science & technology corridor has already launched the Risk of Ovarian Cancer Algorithm (ROCA^®) test which is currently being used by physicians in UK and USA.

In UK it is being used by private clinics and in USA it is available in 5 states namely Arizona, Illinois, Massachusetts, New Jersey and Texas on a self pay basis.

ROCA was co-invented by Professor Ian Jacobs and Dr Steve Skates, and was developed by analyzing the serum CA125 profiles of over 27,000 women, some of whom developed ovarian cancer, in a series of clinical trials in the UK and Sweden. 

The ROCA Test is a quantitative algorithm that takes into account women’s age, menopausal status, and CA125 levels over time to produce a score that indicates her likelihood of having ovarian cancer. The women serve as their own control when they are serially tested for CA 125.

The ROCA Test is the first step in a multi-modal assessment for ovarian cancer and is to be used to help physicians assess whether a woman should undergo additional testing, including transvaginal ultrasound scan of the ovaries.

The ROCA test is intended for:

• Post-menopausal women aged between 50 and 85, with no known ovarian cancer risk factors, 
• Women between 35 and 85, who are considered to be at high risk of ovarian cancer due to a family history of ovarian or breast cancer, 
• Women with mutation in specific genes such as the BRCA1 or BRCA2 or Lynch Syndrome genes.

The standard cut-off for healthy baseline levels of CA125  is 35 unit-per-millilitre (U/ml), but the levels show a considerable variation , including many cases where their baseline level are well above the standard. Moreover, some women with ovarian cancer have changing levels of CA125 that are well below this cut-off and therefore can be missed.

The ROCA Test reports a numerical score for the risk for ovarian cancer e.g. 1 in 5,000. In the clinical trials that validated ROCA, this risk score was then categorized as ‘Normal’, ‘Intermediate’ or ‘Elevated’ as a guide for clinical decision making on further follow up, such as transvaginal ultrasound scan.

Based on these levels, their risk of ovarian cancer (ROC) was interpreted on the algorithm as:

• normal – return to annual screening
• intermediate – repeat CA125 in 12 weeks (repeat level I screen)
• elevated – repeat CA125 and transvaginal ultrasound in six weeks (level II screen) with earlier screens arranged where clinically suspicious

The test detected 86 percent of ovarian cancers with specificity of 99.8 percent. By comparison, conventional fixed CA125 cutoffs of 35 U/ml or 30 U/ml identified 41 percent and 48 percent, respectively.

A separate randomized, prospective trial - the United Kingdom Familial Ovarian Cancer Screening Study (UKFOCSS) - evaluated ROCA in over 4,000 women who had a family history of ovarian/breast cancer, and/or a genetic predisposition to ovarian/breast cancer. Out of BRIP1, BARD1, PALB2 and NBN, it was estimated that the risk of ovarian cancer for women with the BRIP1 mutation was 3.4 times greater than that of the UK general population.

In a similar study led by MD Anderson Cancer Center researcher Karen Lu and published in the journal Cancer in 2013, the ROCA test was able to 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.

Lu and her colleagues at MD Anderson are also continuing their evaluation of the test separate from Abcodia's efforts, and the trial first detailed in the 2013 Cancer study is ongoing. Lu is also co-leading with Skates a study evaluating the test in a high-risk population.

"It's a public health standard for cancer screening that there has to be a decrease in mortality before a cancer screening test is recommended for the general public," she said. "So while the UK study and the US study have shown promise, it is really important to wait for the definitive [mortality and survival] data before using it outside a research setting."

Meanwhile, the Ovarian cancer national Alliance stresses the importance of more long term follow up of the UKCTOCS trial, more long term  mortality data and  a discussion with the scientific community to understand how the test will fit into the preventive strategies for the ovarian cancer.

Abcodia is going to be pursuing FDA approval for the test.

Limitations of the ROCA^®test:

• The ROCA^® Test is not intended to be used as the only test to determine whether the patient has a ovarian malignancy and the patient should proceed to surgery. The ROCA^® Test is only intended to provide you with a risk score that can help you to determine your patient's need for a transvaginal ultrasound screen, further imaging tests and other clinical assessment.
• The ROCA^® Test fails to detect all ovarian cancers. Up to 15 out of every 100 ovarian cancers in women having screening with the ROCA^® Test may be missed. Therefore, it is still very important that the patients and physician should  remain aware of the symptoms of ovarian cancer based on the history, demographic and physical findings.

Financial disclosure:

Two study authors of  UKCTOCS are co-inventors of the risk of ovarian cancer algorithm (ROCA), which is patented and licensed to Abcodia Ltd.
Two other study authors also declare financial interests through Abcodia Ltd.
One of the authors declared a consultancy arrangement with Becton Dickinson in the field of tumour markers. The remaining authors declare no conflicts of interest.

Reference:

http://www.businessweekly.co.uk/news/biomedtech/ovarian-cancer-test-rolled-out-across-five-us-states

https://www.morningstar.com/news/pr-news-wire/PRNews_20151202enUK201512027811/abcodia-announces-initial-us-availability-of-the-roca-test-to-aid-in-the-early-detection-of-ovarian-cancer.print.html

http://www.nhs.uk/news/2015/05May/Pages/New-ovarian-cancer-screening-technique-twice-as-effective.aspx

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2815%2901224-6/abstract
http://www.ovariancancer.org/2015/12/16/statement-coming-soon/
http://www.cancer.gov/types/ovarian/hp/ovarian-screening-pdq

Menon U, Ryan A, Kalsi J, et al. Risk algorithm using serial biomarker measurements doubles the number of screen-detected cancers compared with a single-threshold rule in the United Kingdom Collaborative Trial of Ovarian Cancer Screening [published online May 11, 2015]. J Clin Oncol. doi:10.1200/JCO.2014.59.4945.

 Bonislawski A. Abcodia to launch ROCA ovarian cancer test in UK and US this year. Genomeweb. 2015. https://www.genomeweb.com/proteomics-protein-research/abcodia-

Menon, U, et al. (2014). Ovarian cancer screening-current status, future directions. Gynaecological Oncology, 132(2), pp. 490-495.

Skates, S (2012). Ovarian Cancer Screening: Development of the Risk of Ovarian Cancer Algorithm (ROCA) and ROCA Screening Trials. International Journal of Gynaecological Cancer, 22, S24-S26.