In November 2022, the Journal of Medical Genetics published a paper that presents the results of a pilot national surveillance programme using the ROCA Test, for women with alterations in the BRCA1 and BRCA2 genes. The study was called ALDO, meaning ‘Avoiding Late Diagnosis of Ovarian cancer’. The paper is co-authored by 26 UK based clinical experts in the field of genetics and / or ovarian cancer. The study was conducted in collaboration with the North Central London Cancer Alliance who co-funded the work with Abcodia Ltd (now GENinCode Plc).
This paper is another incredibly important step forward in being able to detect ovarian cancer earlier. In this blog, we aim to explain why.
Background
Up to 4 out of every 10 women who carry alterations in the one of two genes, BRCA1 or BRCA2 will develop ovarian cancer. Ovarian cancer is a severe form of cancer that is typically diagnosed late when the cancer has spread. Symptoms can be confused with other more common illnesses and as a result, diagnosis is often slow. There are currently few options for these women. Depending on the specific BRCA gene alteration, doctors will generally recommend that a woman undergoes surgery to prevent ovarian cancer from developing. This involves removing both ovaries and fallopian tubes. However, this surgery will lead to a woman being unable to have a baby and it will trigger menopause if conducted in young women. Because of this, many women opt to delay surgery to allow them time to build their families and until they get closer to the natural menopause. The downside to such a delay is that they are left at risk of developing late-stage ovarian cancer. Having a routine test to look for ovarian cancer during this time may therefore be helpful.
What is the ROCA Test
The ROCA Test is an algorithmic method that assesses the likelihood that a woman has ovarian cancer, based on changes in a cancer antigen, CA125 found in the blood. If a woman’s ROCA score is outside the normal range, she would be referred for an examination of her ovaries using an ultrasound test. The ROCA Test works by building up a profile of the levels of CA125 which generally increases as ovarian cancer develops. As soon as there is a small change in a woman’s CA125 level, the ROCA Test will ‘flag’ a woman for an ultrasound test. In this way, the ROCA Test has been shown to identify more women with earlier stage ovarian cancer, when no obvious symptoms are apparent. Two previous academic trials, one in the UK and one in the US have shown that surveillance using the ROCA method can detect more ovarian cancers at an earlier stage.
Aims of the ALDO Study
The key objective of the ALDO study was to assess whether similar results could be seen when tested within the NHS, which strives to improve longer term outcomes for cancer and patient experience. The study was set up in 2017.
The Results
The ALDO study offered the ROCA Test to 767 women, aged between 35 to 83. All women carried an alteration in the BRCA1 or BRCA2 gene and had decided to defer preventative surgery. The women received the ROCA Test for an average of 1.7 years, so up to 6 tests during the study period.
During that time, most of the women (584) completed surveillance without having any abnormal ROCA results. All those women remained free from ovarian cancer during this period.
Nineteen women (2.5%) had surgery prompted by abnormal ROCA test results. Ovarian cancer was highly suspected in 8 of these women, 6 of which were confirmed to have ovarian or fallopian tube cancer at the time of their surgery. The two women who did not have ovarian cancer were diagnosed with endometriosis and ovarian cysts.
Of the six women picked up by the ROCA Test and diagnosed with ovarian cancer, half of these (3) were earlier stage disease (no visible tumour beyond the pelvis). During the surgery, in 5 out of the 6 women, it was possible to remove all the visible tumour. No patients required chemotherapy before surgery, which is common if women are diagnosed with tumours that are diagnosed late.
The paper helpfully provides a summary diagram from ALDO, plus the two previous academic studies in the UK and US, of the stages of ovarian cancers detected during ROCA surveillance compared to no surveillance. This diagram shows that if the ROCA Test is started before any ovarian cancer starts to develop (incident ovarian cancer), the stage at which ovarian cancer can be detected using the ROCA Test is reduced significantly, with only 53% being stages 3b, 3c and 4, compared to over 90% if women do not undertake ROCA surveillance.
Another observation from this study is that of the 3 of the 6 women detected by the ROCA Test to have ovarian cancer, the CA125 blood level was normal (i.e. less than 35U/ml). In addition, in 4 of the 6 women, there was no obvious tumour visible on the ultrasound scan. In all these women, without the ROCA Test to trigger further investigations, the cancer diagnosis would have taken longer and only occurred as symptoms developed.
Take Home Messages
Surveillance using the ROCA Test may be helpful ahead of preventative surgery.
If a woman is unfortunate to develop ovarian cancer during this period, it is more likely that the tumour will be small and it will be easier to remove it fully.
If a woman does decide to defer preventative surgery, then starting the ROCA Test as soon as that decision is made, is important. The ROCA Test has more chance of detecting ovarian cancer earlier if it can use CA125 levels determined before any cancer starts to develop.
How does the ROCA Test compare with other tests
There is no other surveillance test that has shown to detect ovarian cancer early. The use of a standard CA125 test (without the ROCA algorithm) or the ultrasound test have proven unable to detect ovarian cancer earlier
Key Limitations of the ROCA Test
The ROCA Test should not be viewed as an alternative to preventative surgery. If a woman opts to take the ROCA Test, it is always important to continue to evaluate whether the time is right for that preventative option.
Despite the ROCA Test being proven through these studies to detect ovarian cancer earlier, there is no evidence that ROCA surveillance can save lives. The ultimate benefit of any surveillance test is the ability to detect cancer early enough to reduce the number of deaths due to cancer compared to deaths without surveillance. There have been no studies in women with an alteration in the BRCA1 or BRCA2 gene to test this.
Availability of the ROCA Test
Currently, the ROCA Test can be obtained via ROCA Care from a number of private clinicians in the UK. The NHS does not yet offer surveillance for women with a confirmed alteration in the BRCA1 or BRCA2 gene, if they have chosen to defer preventative surgery. However, this is currently under review by NICE.