Earlier detection of ovarian cancer by monitoring serum cancer antigen 125 (CA-125)
The symptoms of ovarian cancer are fairly non-specific and the diagnosis is often delayed, so the condition is a candidate for a screening program. Serum cancer antigen 125 (CA-125) concentration has not been used for screening to date, because it is raised in patients with ovarian cancer only at a late stage and is also raised in diseases such as pelvic inflammatory disease and endometriosis.
A study published online in the Journal of Clinical Oncology on 11 May 2015 reported on more than 46,000 women at average risk of ovarian cancer who participated in the multimodal screening arm of the UK Collaborative Trial of Ovarian Cancer Screening. The women had their CA-125 concentrations measured at least once each year, usually over three years, between 2001 and 2011. The results were interpreted using a ‘risk of ovarian cancer algorithm’ (ROCA) based on age and whether or not CA-125 concentrations changed with time.
Women with a significantly increasing CA-125 value above their own baseline were considered to have an elevated risk and were offered a repeat CA-125 blood test and a vaginal ultrasound examination after six weeks (or earlier if there were suspicious signs and symptoms). Those with a relatively flat CA-125 profile were thought to have a normal risk and continued with an annual CA-125 blood test. Women with an intermediate CA-125 profile had a repeat CA-125 test after 12 weeks. A maximum of three flat or intermediate annual CA-125 tests were requested to minimise anxiety resulting from repeat testing. Women who remained in the intermediate group after three years were offered an ultrasound scan. All women with an abnormal ultrasound scan were referred clinically for further investigation and surgery if necessary.
The ROCA procedure correctly assessed as not at risk the 99.8% of women who did not have cancer. It also correctly identified 86% of those women who did have cancer. In contrast, the conventional single CA-125 cut-off of greater than 35 U/mL identified less than half (41%) of those with cancer.
Professor Usha Menon, trial co-ordinator at University College London commented: “There is currently no national screening programme for ovarian cancer, as research to date has been unable to provide enough evidence that any one method would improve early detection of tumours. These results are therefore very encouraging. They show that use of an early detection strategy based on an individual’s CA-125 profile significantly improved cancer detection compared to what we’ve seen in previous screening trials.”
Later this year the UK Collaborative Trial of Ovarian Cancer Screening will report results from the other two arms of the trial (women who were screened by ultrasound scan alone and a control group who were not screened) together with the most important factor for a cancer screening program: the number of lives saved.
The research was funded by the Medical Research Council, Cancer Research UK, the Department of Health and the Eve Appeal.