Biomarker Velocity Outweighs Single Threshold In Ovarian Cancer Detection

UK researchers detect more incidences of ovarian cancer using an algorithm incorporating serial measurements of CA125 compared with models using a single threshold value

medwireNews: A risk algorithm that uses serial measurements of the biomarker CA125 can detect twice as many incidences of invasive epithelial ovarian cancer (iEOC) as methods using a single fixed cutoff, finds a UK-based study.

Although the effect of such screening on ovarian cancer-related mortality will only be known once follow-up is complete, “our current findings are of immediate importance as they highlight the need to examine serial change in biomarker levels in the context of screening and early detection of cancer”, says the team led by Usha Menon, from University College London.

A total of 46,237 postmenopausal women randomly assigned to the multimodal strategy arm of the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) underwent incidence screening, involving an annual assessment of serum CA125 levels. An individual’s risk of developing ovarian cancer was evaluated using the Risk of Ovarian Cancer Algorithm (ROCA), which took into account the individual’s age and their baseline CA125 levels as well as how they changed over time. These results were then compared with those of cases and controls to assign risk.

Screen-positive surgery was performed in 640 (0.2%) of 296,911 screens, with primary ovarian or tubal tumours detected in 154 women, including 133 cases of iEOC. And twenty-two interval iEOCs were diagnosed within a year of the most recent incidence screen, one of which was in a woman estimated to be at high risk but who was not referred for surgery as per protocol, the team reports.

Using ROCA alone resulted in an iEOC detection rate of 86.4% (134 of 155), whereas if fixed cutoffs of annual CA125 levels had been used, the rate would have been 41.3%, 48.4% and 66.5% for levels greater than 35 U/mL, 30 U/mL and 22 U/mL, respectively.

And the area under the curve for ROCA was significantly higher than that for fixed cutoffs.

“The numbers of unnecessary operations and complications were within acceptable limits and we were able to safely and effectively deliver screening for over a decade across 13 NHS Trusts”, said Usha Menon in a press release.

The researchers conclude in the Journal of Clinical Oncology: “[O]ur data support use of velocity based algorithms as opposed to a predefined single threshold [rule] in cancer screening strategies using blood biomarkers.”


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.J Clin Oncol 2015; Advance online publication 11 May. doi: 10.1200/JCO.2014.59.4945

medwireNews ( ) is an independent medical news service provided by Springer Healthcare Limited. © Springer Healthcare Ltd; 2015