A national study of more than 250,000 patients with ovarian cancer in the United States found that cancer antigen 125 levels at diagnosis could vary by race. 

Black and American Indian patients were significantly less likely to have elevated levels compared with White patients, raising concerns that current diagnostic thresholds may not be equally effective for all populations.

Cancer antigen 125 (CA-125) is a blood protein often elevated in patients with ovarian cancer. It is used internationally to help determine whether patients with a pelvic mass should be referred to a gynecologic oncologist. Most clinical guidelines define CA-125 levels of 35 units/mL or higher as elevated.

Investigators used data from the U.S. National Cancer Database, which covers over 70% of new cancer cases nationwide. Among 212,477 patients with measured CA-125 levels, 88.2% had elevated values at diagnosis. After adjusting for stage, comorbidities, and menopausal status, Black patients were 23% less likely to have elevated CA-125 levels compared with White patients. American Indian patients had similarly lower odds.

This pattern persisted when analyzing high-grade serous tumors, the most common and aggressive ovarian cancer subtype. In contrast, Asian patients showed a slightly higher risk of elevated CA-125 in certain subgroups.

Patients with nonelevated CA-125 levels experienced treatment delays. Among those with stage II to IV disease, patients with false-negative CA-125 results began chemotherapy an average of 9 days later compared with those who had elevated levels. Among Black patients, this delay extended up to 5 days longer compared with White patients when CA-125 levels weren't elevated.

The CA-125 threshold of 35 units/mL was established in the early 1980s based on data from predominantly White populations. More recent research has shown that baseline CA-125 levels can differ by race, even among healthy individuals. This raises the possibility that current thresholds may miss cases in racially diverse populations.

Study investigators noted that relying solely on existing CA-125 cutoffs may contribute to delayed diagnoses and treatment, particularly among historically underserved groups. They recommended further research to develop inclusive diagnostic guidelines that are sensitive to population-level differences.

The findings underscored the importance of evaluating how diagnostic tools are developed and applied, especially when they influence access to timely specialist care. Because ovarian cancer is often diagnosed at advanced stages, even modest treatment delays can have clinical consequences. The study added to evidence necessitating the prioritization of equity in cancer diagnostics.

Disclosures and funding information are available in the original study.

Source: JAMA Network Open