Cancer Antigen 125 Levels at Time of Ovarian Cancer Diagnosis by Race and Ethnicity
Authors: Anna Jo Bodurtha Smith, Emily Gleason, Sneha Kadiyala, Xingmei Wang, Elizabeth A. Howell, Anne Marie McCarthy
Journal: JAMA Network Open (2025)

Importance International guidelines use cancer antigen (CA) 125 thresholds to recommend which patients with pelvic masses should undergo evaluation by gynecologic oncologists for ovarian cancer. However, CA-125 thresholds were developed from White populations. If CA-125 levels differ among patient populations, current guidelines may contribute to delayed ovarian cancer diagnoses among women of other races and ethnicities than White. Objective To examine CA-125 levels at ovarian cancer diagnosis by patient race and ethnicity and associations of elevated CA-125 levels with timely treatment. Design, Setting, and Participants This retrospective cohort study included all patients with ovarian cancer diagnosed between January 1, 2004, and December 31, 2020, using the US National Cancer Database. The data analysis was performed between November 1, 2023, and July 10, 2024. Exposure Patient race and ethnicity as identified in the National Cancer Database. Main Outcome and Measures Cancer antigen 125 level was defined as elevated or borderline and negative or normal. Multivariable logistic regression models were used to examine the association of patient race and ethnicity with CA-125 level overall and for epithelial and high-grade serous cancers. Generalized linear models were used to examine the association of CA-125 level with days from diagnosis to chemotherapy start for patients with stage II to IV ovarian cancer. Results Of the 250 749 patients with ovarian cancer diagnosed between 2004 and 2020 (median [IQR] age, 62.0 [52.0-73.0] years; 0.4% American Indian, 3.7% Asian, 8.6% Black, 85.2% White, and 2.0% other or unknown race and 6.7% Hispanic, 88.8% non-Hispanic, and 4.6% of unknown ethnicity), 212 477 had measured CA-125 levels, and 88.2% had an elevated CA-125 level at diagnosis. Patients with American Indian, Asian, or Black race were less likely to have an elevated CA-125 level at ovarian cancer diagnosis than White patients. In multivariable analyses adjusted for stage, comorbidities, and menopausal status, Black patients had lower odds of elevated CA-125 levels (adjusted odds ratio [AOR], 0.77; 95% CI, 0.74-0.81) compared with White patients, as did American Indian patients (AOR, 0.77; 95% CI, 0.62-0.94). Among patients with high-grade serous ovarian cancer only, Black patients had a lower odds of having an elevated CA-125 level at diagnosis (AOR, 0.81; 95% CI, 0.73-0.91). Patients with stage II to IV ovarian cancer with false-negative CA-125 findings at diagnosis had 9.38 days longer (95% CI, 8.43-10.34 days) to chemotherapy start compared with patients with an elevated CA-125 level. Conclusions and Relevance In this cohort study of patients with ovarian cancer, American Indian and Black patients were 23% less likely to have an elevated CA-125 level at diagnosis. Current CA-125 thresholds may miss racially and ethnically diverse patients with ovarian cancer. Work is needed to develop inclusive CA-125 thresholds and diagnostic guidelines and not compound disparities in ovarian cancer diagnosis and treatment.