The first FDA-approved biomarker for ovarian cancer diagnosis was cancer antigen (CA) 125, which was initially reported in 1981. It is detected through blood analysis and produced by ovarian cancer cells. The discovery of CA-125 was a significant advancement, as ovarian cancer signs and symptoms are often mild, allowing for earlier detection and the triage phase, which increased survival rates.
International guidelines currently include a 35 U/mL threshold for gynecology oncology referrals. However, levels of CA-125 differ by race, with Native American and Black women having lower levels, which potentially leads to delayed or missed diagnosis. This underscores the need for diverse biomarker validation. The recent study published in JAMA Network Open aimed to investigate the racial and ethnic differences in CA-125 levels during diagnosis of ovarian cancer and the relationship between raised CA-125 levels and treatment time.
In this retrospective cohort study, U.S. patients with ovarian cancer were selected from the National Cancer Database (NCDB) for the period spanning January 1, 2004, to December 31, 2020. The primary endpoint was the presence of increased levels of CA-125 at diagnosis, and the secondary endpoint was the time to start treatment (chemotherapy) among patients with advanced stages II-IV ovarian cancer. The association between the racial-ethnicity of patients and CA-125 levels was measured using multivariable logistic regression analysis. The correlation of CA-125 levels from diagnosis to the start of chemotherapy in patients with stage II-IV ovarian cancer was estimated by generalized linear analysis. All statistical analysis was conducted through SAS, version 9.4. Â
A total of 250,749 patients were included in this study. The median age of patients was 62 years, with an interquartile range (IQR) of 52 to 73 years. The racial distribution included 85.2% White, 0.4% American Indian, 8.6% Black, 3.7% Asian, and 2% other race. Regarding ethnicity, 6.7% were Hispanic, 88.8% were non-Hispanic, and 4.6% were unknown.
The results showed that 88% of patients had elevated CA-125 levels among 212,477 patients with estimated CA-125 levels at diagnosis. Higher CA-125 levels were found to be less common in Asian, Black, and American Indian patients compared to White patients. Â
Black and American Indian patients were less likely to have increased CA-125 levels compared to White patients with an adjusted odds ratio (AOR) of 0.77 (95% confidence interval [CI], 0.74-0.81) and 0.77 (95% CI, 0.62-0.94), respectively in a multivariable model that adjusted for comorbidities, menopausal status, and cancer stages. Black patients were less likely to have higher levels of CA-125 during diagnosis of high-grade serous ovarian cancer (HGSOC) patients with an AOR of 0.81 (95% CI, 0.73-0.91).
It was observed that black patients had a lower incidence of raised CA-125 levels at every stage of cancer compared to White patients. While 10.9% of Black patients with stage III-IV ovarian cancer had non-elevated levels of CA-125 compared to 8.2% of White patients.
Increased CA-125 levels were associated with a 9.38-day shorter time to start chemotherapy among treatment-recommended patients with stage II to IV with a 95% CI of 8.43-10.34 days. Black patients experienced 3.26 days (95% CI, 2.43-4.09 days), and Hispanic patients had 3.51 days (95% CI, 2.52-4.51 days) longer time to start treatment compared to White patients. Â
This study’s limitations include NCDB covering only 85% of ovarian cancer cases, potential ethnic bias, varying CA-125 threshold, and lack of ancestry data.
In conclusion, this study found that American Indian and Black patients with ovarian cancer had a 23% lower likelihood of having increased CA-125 levels at diagnosis compared to White patients. Further research is required to establish CA-125 thresholds and recommendations to improve the diagnosis of ovarian cancer and reduce disparities. Â Â Â Â Â Â Â Â Â
Reference: Smith AJB, Gleason E, Kadiyala S, Wang X, Howell EA, McCarthy AM. Cancer antigen 125 levels at time of ovarian cancer diagnosis by race and ethnicity. JAMA Netw Open. 2025;8(3):e251292. doi:10.1001/jamanetworkopen.2025.1292
