Why we measure it

Ovarian cancer is the most lethal gynaecological malignancy. The five-year survival rate for stage I ovarian cancer is approximately 90%; for stage IV it is below 30%. The survival gap between early and late-stage disease is one of the largest of any solid tumour — and ovarian cancer produces early-stage symptoms that are so non-specific (bloating, early satiety, urinary frequency) that the majority of women are diagnosed only after the disease has spread beyond the ovary. The clinical case for annual CA-125 testing is this asymmetry: if a rising trend detects even a fraction of ovarian cancers at stage I rather than stage III, the survival benefit is substantial. The UK Collaborative Trial of Ovarian Cancer Screening (UKCTOCS) — the largest ovarian cancer screening trial ever conducted, with over 200,000 postmenopausal women followed for a median of 16.3 years — found that the multimodal strategy using serial CA-125 interpreted via the Risk of Ovarian Cancer Algorithm (ROCA), which uses the individual's own CA-125 trend rather than a fixed threshold, detected cancers at significantly earlier stage than the control group. The trial found a 40% reduction in mortality in the first 14 years in the multimodal screening group, though this did not reach conventional statistical significance in the primary analysis. The ROCA approach — which is the direction of modern CA-125 interpretation — is explicitly trend-based: it calculates the probability of ovarian cancer from the rate and pattern of CA-125 change, not from any single absolute value. Annual measurement in the Blueprint protocol provides the serial data that makes this approach possible.

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. Any of these findings warrants clinical review, including consideration of transvaginal ultrasound and specialist assessment.

In the protocol