As reported in a paper published in the journal Clinical Cancer Research, two ovarian cancer screening trials imply that a protocol involving quarterly blood test to identify significant increases above each patient’s personal baseline in levels of the protein CA125, followed by ultrasound examination when such elevations are detected, could reduce the risk of diagnosis with advanced cancer in high–risk women who choose to delay recommended preventive surgery.

The two trials reported in the current paper utilize the Risk of Ovarian Cancer Algorithm (ROCA) – co–developed by Skates and Ian Jacobs, MD, FRCOG, of the University of New South Wales in Australia and University College London – which tracks CA125 levels over time to identify significant elevations above each patient’s baseline levels, even those that do not exceed the traditional threshold of 35. One trial conducted through the National Cancer Institute’s Cancer Genetics Network (CGN) – with additional patients from two ovarian Specialized Programs of Research Excellence (SPORE) and two Early Detection Research Network sites (EDRN) – was led by Skates. The other, conducted through the Gynecologic Oncology Group (GOG), was led by Mark H. Greene, MD, of the Clinical Genetics Branch at the National Cancer Institute (NCI).

Both trials followed similar protocols, enrolling women at elevated risk for ovarian cancer – based on either a strong family history of ovarian and/or breast cancer or the presence in the patient or in close blood relatives of risk–associated mutations in the BRCA1 or BRCA2 genes – who had not yet had risk–reducing surgery. Participants had CA125 blood tests utilizing ROCA every three months, compared with screening for raised CA125 values every 6 or 12 months as in previous screening studies. The investigators calculated a patient’s ROCA risk by analyzing the results of each new CA125 test, combined with previous results, and factors such as participant’s age and menopausal status.

Women at intermediate ROCA risk were referred for an ultrasound examination, while those at an elevated ROCA risk received both ultrasound and clinical evaluation by either a gynecologic oncologist or the site principal investigator. While the results of those examinations were used to guide decisions about surgical treatment, study participants were free to choose to have their ovaries and fallopian tubes removed at any time during the clinical trials, as is standard practice for women with a BRCA1/2 mutation. Between 2001 and 2011, the CGN trial enrolled 2,359 women at 25 U.S. sites. The GOG trial enrolled 1,459 women at 112 sites in the U.S. and Australia between 2003 and 2006 and screened them for five years. Among the more than 3,800 participants in both studies, 19 malignant tumors of the ovaries or fallopian tubes were identified during the study periods. Ten cases were diagnosed during screening, and nine were diagnosed by preventive surgery.

Of the ten cases, there was evidence that four were present at the outset of the trial, while six tumors were likely to have developed during the trial period after a CA125 baseline had been measured. While the algorithm can calculate risk without a baseline, ROCA works best when a baseline has been established. The results in these six cases reflect the benefits of a long–term ROCA screening program; all but one were diagnosed by ROCA, giving a sensitivity of over 80 percent ,and 50 percent were detected at early stages.

Another study – the UK Familial Ovarian Cancer Screening Study, led by ROCA co–developer Jacobs and published in the Journal of Clinical Oncology – found that a similar protocol using ROCA–based testing every four months was also better than current practice at diagnosing early–stage tumors in high–risk women.