CA-125
Cancer Antigen 125
What it is
CA-125 (Cancer Antigen 125) is a high-molecular-weight glycoprotein expressed on the surface of certain epithelial cells, including those of the ovaries, fallopian tubes, uterus, and other pelvic structures. It is shed into the bloodstream where it can be measured by immunoassay. CA-125 was first characterised by Bast and colleagues in 1983 using a monoclonal antibody (OC125) raised against an ovarian cancer cell line, and it remains the most widely used blood-based marker for ovarian cancer. CA-125 is elevated in approximately 80% of advanced (stage III–IV) epithelial ovarian cancers, but in only 50–60% of early-stage (stage I–II) cancers — a limitation that has driven significant research into supplementary markers (including HE4 and the ROMA algorithm) and ultrasound-based approaches. Critically, CA-125 is not cancer-specific: it is elevated in endometriosis, uterine fibroids, pelvic inflammatory disease, liver disease, and early pregnancy, and it fluctuates with the menstrual cycle in premenopausal women. This non-specificity means that a single elevated reading has limited positive predictive value in the general population — but a rising trend across serial annual measurements, particularly in postmenopausal women, is a fundamentally different and more informative signal.
Why we measure it
CA-125 is a protein shed into the blood by cells lining the ovaries and other pelvic tissues, and it has been studied for decades in relation to ovarian cancer. That research is shaped by a stark statistic: five-year survival for ovarian cancer is about 90% at stage I and below 30% at stage IV, and early symptoms (bloating, early fullness, urinary frequency) are easy to miss. The largest trial, the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS), followed over 200,000 postmenopausal women for a median of 16.3 years. Interpreting each woman's own CA-125 trend with the Risk of Ovarian Cancer Algorithm (ROCA), rather than a fixed threshold, identified cancers at an earlier stage — although the mortality reduction did not reach statistical significance in the primary analysis. Modern research on CA-125 is therefore trend-based, and annual measurement in the Blueprint protocol builds the personal series that approach relies on. CA-125 is not diagnostic on its own — many non-cancer conditions raise it.
Why every 12 months
The informational value of CA-125 is almost entirely a function of trend, not threshold. A CA-125 of 42 U/mL — technically elevated above the standard 35 U/mL cutoff — in a woman who has had stable readings of 38–44 U/mL for five years carries a different clinical meaning than one who was at 12 U/mL two years ago. Annual testing establishes the personal baseline from which meaningful deviation can be detected. It also provides the longitudinal data needed for ROCA-type interpretation, which requires at least two prior readings to compute a meaningful risk estimate. For premenopausal women, menstrual cycle phase and the presence of conditions like endometriosis need to be considered in interpretation; for postmenopausal women, where the non-specific causes of elevation are less prevalent, CA-125 has higher specificity and the trend signal is stronger.
What movement means
The standard clinical reference value for CA-125 is below 35 U/mL (units per millilitre), derived from the distribution in a healthy reference population. This threshold was designed for monitoring known ovarian cancer, not for population screening — its positive predictive value as a screening cutoff in the general population is low, because benign causes of elevation are far more prevalent than ovarian cancer. The most important clinical signals are: a sustained rise across consecutive annual measurements; a reading that has crossed above the individual's own historical range; or a level above 200 U/mL, where the likelihood of malignancy versus benign disease increases substantially. Research treats any of these findings as a reason to discuss with a registered medical practitioner.
Normal
< 35 U/mL
Within the standard reference range. The trend across consecutive annual draws is more informative than the absolute level. A stable value within this range, tracked over years, provides a meaningful personal baseline.
Bast RC Jr et al., New England Journal of Medicine, 1983 — doi:10.1056/NEJM198307143090203
Borderline
35 – 200 U/mL
Above the standard reference cutoff, but this range overlaps substantially with non-cancer causes (endometriosis, fibroids, pelvic inflammatory disease, liver conditions). Research gives more weight to this range after menopause, or when it follows a rising trend from a lower baseline. CA-125 is not diagnostic on its own. Discuss with a registered medical practitioner.
Jacobs IJ et al., The Lancet, 2016 — doi:10.1016/S0140-6736(15)01224-6
Significantly Elevated
> 200 U/mL
Markedly above range. Studies report that the likelihood of a significant cause rises at this level, although non-cancer causes remain possible. CA-125 is not diagnostic on its own. Discuss with a registered medical practitioner.
Jacobs IJ et al., The Lancet, 2016 — doi:10.1016/S0140-6736(15)01224-6
This page summarises published research for general education. It is not medical advice and does not interpret individual results. Discuss your results with a registered medical practitioner.
In the protocol
References
- 1.
Bast RC Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. “Reactivity of a Monoclonal Antibody with Human Ovarian Carcinoma.” Journal of Clinical Investigation. 1981.
- 2.
Jacobs IJ, Menon U, Ryan A, et al.. “Ovarian Cancer Screening and Mortality in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A Randomised Controlled Trial.” The Lancet. 2016.
- 3.
Menon U, Gentry-Maharaj A, Burnell M, et al.. “Ovarian Cancer Population Screening and Mortality after Long-term Follow-up in the UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS): A Randomised Controlled Trial.” The Lancet. 2021.
- 4.
Skates SJ, Xu FJ, Yu YH, et al.. “Toward an Optimal Algorithm for Ovarian Cancer Screening with Longitudinal Tumor Markers.” Cancer. 1995.