Glycovariants of CA-125 in the early detection of ovarian cancer
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Importance
Two randomized trials have shown that screening with CA-125 is not of value for reducing ovarian cancer mortality. This appears to be because changes in CA-125 occur too late in the disease process to allow for surgical cure of early-stage disease.
Objective
To determine whether glycovariants of CA-125 could detect ovarian cancer years before clinical diagnosis.
Design
Case-control study of cryopreserved blood samples and data from the population-based Malmö Diet and Cancer cohort.
Setting
Population-based study in Sweden.
Participants
Serum was available for 17,297 women aged 44 – 73 collected at baseline in 1991-1996 and from 2,168 women re-sampled in 2007-2012. Participants’ records were linked to the Swedish cancer registry to identify 82 women with incident ovarian cancer diagnosed up to 10 years after blood draw. Cases were matched 1:3 with controls by age and venipuncture date.
Exposure
Serum was measured for CA-125 glycovariants Sialyl-Thomsen-nouveau (STn) and Macrophage-Galactose-Lectin (MGL) using GLYVAR ® Ovarian I and II assays (Uniogen), conventional CA-125 (CanAg CA125 EIA, Fujirebio) and HE4 EIA (Fujirebio).
Main outcome measure
Ovarian cancer.
Results
The CA-125-STn was associated with subsequent ovarian cancer (p=0.002). In the primary analysis restricted to cases within 5 years, the area-under-the-curve for CA-125-STn was 0.68; with moving window analysis suggesting retained predictiveness up to 5-7 years. Of the cases diagnosed within 5 years, 27% were in the top 5% of CA-125-STn levels (≥2.3 U/ml), with 35% and 49% of cases diagnosed in the top 10% and 20% respectively. Our findings were replicated by independent measurements of a separate aliquot from a subset of cases and controls. Neither CA-125, HE4 nor CA-125 glycovariants detected by MGL importantly predicted subsequent ovarian cancer.
Conclusions and Relevance
CA-125-STn can detect ovarian cancer several years before clinical diagnosis. Further research is warranted on larger cohorts with sequential samples to determine the shape of the relationship between CA-125-STn and risk, the value of longitudinal sampling of CA-125-STn, and whether other markers could be combined with CA-125-STn to more accurately predict ovarian cancer risk.
Key Points
Question
Can glycovariants of CA-125 detect ovarian cancer years before clinical diagnosis?
Findings
In a case-control study of 323 Swedish women followed longitudinally, the Sialyl-Thomsen-nouveau (STn) glycovariant of CA-125, but not conventional CA-125 or other markers, predicted ovarian cancer. Close to half of ovarian cancer cases within 5 years of blood sample occurred in the patients with the top 20% of CA-125-STn glycovariant levels.
Meaning
CA-125-STn can detect ovarian cancer several years before clinical diagnosis.
