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.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.
