Racial Differences in CA-125 Levels Tied to Ovarian Cancer Treatment Delays

Current cancer antigen 125 (CA-125) thresholds may miss racially and ethnically diverse patients with ovarian cancer, resulting in delayed chemotherapy initiation, according to a study published in JAMA Network Open.¹

CA-125, a protein produced by ovarian cancer cells and detectable through a blood test, became the first FDA-approved biomarker for cancer diagnosis and surveillance in 1981. Its discovery marked a breakthrough in diagnosing and triaging suspected ovarian cancer, particularly because patient symptoms can be subtle and easily attributed to benign conditions.

Consequently, CA-125 has been incorporated into national and international ovarian cancer guidelines. For example, the American College of Obstetrics and Gynecology recommends that postmenopausal women with an elevated CA-125 level and a pelvic mass be referred to or evaluated by a gynecologic oncologist.² Based on findings from the original 1981 study, most guidelines consider a CA-125 level of 35 U/mL or greater to be elevated.³

However, the original studies were conducted in Boston, Massachusetts, and validated in Minnesota, where the patient populations were predominantly White (80% in Boston; 98% in Minnesota).⁴ Compared with non-Hispanic White women, the researchers found that healthy Black women had CA-125 levels that were 10% to 37% lower, and Native American women had levels up to 20% lower.¹

If these differences persist in patients with ovarian cancer, current guidelines may contribute to missed or delayed diagnoses among women of other racial and ethnic backgrounds. The researchers emphasized the need to validate biomarkers in more diverse populations. To address this, they conducted a study to examine CA-125 levels at ovarian cancer diagnosis by patient race and ethnicity, as well as the association between elevated CA-125 levels and time to treatment.

Black and American Indian women with ovarian cancer were less likely to have elevated cancer antigen 125 (CA-125) levels at diagnosis, resulting in delayed chemotherapy initiation and highlighting the need for more inclusive guidelines. | Image Credit: jarun011 - stock.adobe.com

The retrospective cohort study included all patients diagnosed with ovarian cancer between 2004 and 2020 in the US National Cancer Database (NCDB). Each patient’s CA-125 level was classified as elevated or borderline and negative or normal using the standard threshold of 35 U/mL or greater.

The researchers conducted this analysis from November 1, 2023, to July 10, 2024. They used multivariable logistic regression models to examine the association between race and ethnicity with CA-125 levels overall and specifically for epithelial and high-grade serous cancers. Also, generalized linear models were used to analyze the association between CA-125 levels and time to chemotherapy initiation among patients with stage II to IV disease.

The study population included 250,749 patients diagnosed with ovarian cancer between 2004 and 2020. The median (IQR) age was 62.0 (52.0-73.0) years. Most patients were non-Hispanic (88.8%) and White (85.2%), followed by Black (8.6%), Hispanic (6.7%), Asian (3.7%), and American Indian (0.4%); some were also of other or unknown race (2.0%) and unknown ethnicity (4.6%).

CA-125 levels were measured at diagnosis in 212,477 (84.7%) patients, but non-White patients were less likely to receive this testing. Lower CA-125 measurement rates were also observed among younger patients, those with Medicaid or Medicare, those without insurance, those with lower education levels, and those treated at academic centers.

Among patients with CA-125 data, 88.2% had elevated levels at diagnosis. This proportion rose with each stage, from 68.6% at stage I to 96.7% at stage IV. Black patients were more likely to be diagnosed at advanced stages than White patients (66.0% vs 63.1%). Despite this, Black, American Indian, and Asian patients were less likely to have elevated CA-125 levels at diagnosis than White patients.

Multivariable analyses adjusted for stage, comorbidities, and menopausal status showed that Black (adjusted odds ratio [AOR], 0.77; 95% CI, 0.74-0.81) and American Indian (AOR, 0.77; 95% CI, 0.62-0.94) patients had lower odds of elevated CA-125 levels across all ovarian cancer histologies. Meanwhile, Asian patients were more likely to have elevated CA-125 levels for high-grade serous ovarian cancer (AOR, 1.30; 95% CI, 1.07-1.59).

Among patients with stage II to IV disease recommended to receive chemotherapy, those with elevated CA-125 levels began treatment an average of 9.38 days sooner (95% CI, 8.43-10.34) than those without elevated levels. Time to chemotherapy decreased with increasing disease stage as patients with stage II ovarian cancer received chemotherapy 8.05 days later than those with stage IV disease (95% CI, 7.28-8.82).

As for race and ethnicity, Black (3.26 days; 95% CI, 2.43-4.09) and Hispanic (3.51 days; 95% CI, 2.52-4.51) patients experienced longer delays to chemotherapy initiation than non-Hispanic White patients. In particular, Black patients with elevated CA-125 levels faced a 3.14-day delay (95% CI, 2.29-3.99), and those with nonelevated CA-125 levels had a 4.99-day delay (95% CI, 1.15-8.84).

The researchers acknowledged their study’s limitations, including the NCDB excluding data from patients living in Puerto Rico, those treated by the Veterans Health Administration, and those cared for in small, non–National Cancer Institute–designated cancer centers. As a result, the study population may be less ethnically diverse than the broader US and global ovarian cancer population, which could introduce bias into the findings.

Despite these limitations, they suggested future actions based on their findings.

“Further work is needed to develop inclusive CA-125 thresholds and guidelines for an ovarian cancer diagnosis and prevent compounding disparities,” the authors concluded.

References

1. 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
2. American College of Obstetricians and Gynecologists’ Committee on Practice Bulletins—Gynecology. Practice bulletin no. 174: evaluation and management of adnexal masses. Obstet Gynecol. 2016;128(5):e210-e226. doi:10.1097/AOG.0000000000001768
3. Kadiyala S, Gleason E, McCarthy AM, et al. Diagnostic guidelines for adnexal mass work-up and gynecologic oncology referral: a systematic review. Paper presented at: Society of Gynecological Oncology Annual Meeting on Women’s Cancer; March 14-17, 2025; Atlanta, GA.
4. Race of the population of the United States, by states: 1970. US Census Bureau; 1970. Accessed April 17, 2025. https://www2.census.gov/library/publications/decennial/1970/pc-s1-supplementary-reports/pc-s1-11.pdf