Risk Algorithm Using Serial CA-125 Measurements Increases the Number of Screen-Detected Ovarian Cancers


Key Points

  • A strategy including serial CA-125 measurements interpreted by ROCA had a sensitivity of 85.8% and a specificity of 99.8% for cancer detection.
  • Use of ROCA doubled the number of screen-detected cancers compared with the use of a single CA-125 threshold.

As reported in the Journal of Clinical Oncology by Menon et al, findings in the United Kingdom Collaborative Trial of Ovarian Cancer Screening indicate that the number of screen-detected ovarian cancers is doubled by using the risk of ovarian cancer algorithm (ROCA) with serial CA-125 measurements compared with the use of single CA-125 threshold levels.

Study Details

In the trial, 46,237 women aged ≥ 50 years underwent screening using a multimodal strategy consisting of annual serum CA-125 measurements interpreted with ROCA, with findings classified as follows: normal risk, return to annual screening; intermediate risk, repeat CA-125 measurement; and elevated risk, repeat CA-125 measurement and perform transvaginal ultrasound. Women with a persistently increased risk underwent clinical evaluation. The performance of a single-threshold CA-125 measurement strategy vs ROCA was compared using receiver operating characteristic area under the curve (AUC) analysis.

Screen-Detected Cancers

After 296,911 person-years of annual screening, 640 women underwent surgery, with 133 having primary invasive epithelial ovarian or tubal cancer. Overall, 22 interval cancers occurred within 1 year of screening; 1 was detected by ROCA and was managed conservatively after clinical evaluation. The multimodal strategy had a sensitivity of 85.8% and a specificity of 99.8% for detection of cancers, with 4.8 surgeries per detection of 1 cancer. ROCA alone would have detected 87.1% of cancers, compared with detection of 41.3%, 48.4%, and 66.5% using fixed CA-125 thresholds at the last annual screen of > 35, > 30, and > 22 U/mL. The AUC values were 0.915 for ROCA (0.915) vs 0.869 using single CA-125 thresholds (P = .0027).

The investigators concluded: “Screening by using ROCA doubled the number of screen-detected [invasive epithelial ovarian or tubal cancer] compared with a fixed cutoff. In the context of cancer screening, reliance on predefined single-threshold rules may result in biomarkers of value being discarded.”

Usha Menon, MD, of the Institute for Women’s Health, University College London, is the corresponding author of the Journal of Clinical Oncology article.

The study was supported by the Medical Research Council, Cancer Research United Kingdom, Department of Health, Eve Appeal, and researchers at the National Institute for Health Research University College London Hospital Biomedical Research Centre. For full disclosures of the study authors, visit

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.