A common test for ovarian cancer may be less effective on black and Native American patients, a review of more than 200 000 patients has found.
One of the two most common ways to test for ovarian cancer is to check for elevated levels of a protein called CA-125 in the patient’s blood, according to the American Cancer Society.
But black and Native American women are 23% less likely to have an elevated CA-125 level when diagnosed with ovarian cancer, suggests the study.
The Washington Post reports that the University of Pennsylvania research, published in JAMA Network Open, reviewed the de-identified medical information of more than 200 000 ovarian cancer patients between 2004 and 2020 stored in the US National Cancer Database.
“Current guidelines may contribute to delayed ovarian cancer diagnoses among women of other races and ethnicities than white,” the study authors wrote.
The research that originally identified cancer antigen 125 (CA-125) as a tell-tale sign of ovarian cancer may have been performed on mostly white patients, though the race of the participants was not recorded, they added.
Alistair Forrest, head of genome biology and genetic diseases at the Harry Perkins Institute of Medical Research in Western Australia, who was not involved in the study, said the research added to similar findings published in a United Kingdom study last year.
The University of Pennsylvania study is “important as it recognises that not everyone is the same and that a test which works in one population may not be useful in another”, said Forrest, who researches ovarian cancer.
The study adds to other findings showing differences in health outcomes for ovarian cancer among different racial groups. There are “profound disparities” in ovarian cancer recovery depending on the race of the patient, according to a summary of findings from the 2023 Ovarian Cancer Evidence Review Conference.
The review said that ovarian cancer was most common in Native American and white women but that black patients were about 18% more likely to die of ovarian cancer than white women. There was no difference in mortality outcomes between Hispanic and white patients or Asian and Pacific Islander and white patients, it found.
It said the quality of care provided to each group could be a cause of the increased death rate and also noted that black women were more likely to be diagnosed when the cancer was already at an advanced stage.
Ovarian cancer is the fifth most common cause of cancer death in women in the United States and has an overall five-year survival rate of slightly less than half, the review noted. Survival is strongly correlated with early detection, it added.
The University of Pennsylvania study called for the development of more inclusive CA-125 thresholds and diagnostic guidelines, and for more research to understand why there could be differences in the CA-125 protein among different demographics.
The other most common way of testing for ovarian cancer is a transvaginal ultrasound, which detects unusual masses, said the American Cancer Society. It notes that “not everyone who has ovarian cancer has a high CA-125 level”.
In its early stages, ovarian cancer often causes no symptoms, or causes symptoms that are easy to attribute to less serious conditions such as bloating, abdominal and pelvic pain, trouble eating and the need to urinate more frequently, the organisation said.
“If you have these symptoms more than 12 times a month, see your doctor,” it recommended.
Study details
Cancer Antigen 125 Levels at Time of Ovarian Cancer Diagnosis by Race and Ethnicity
Anna Jo Bodurtha Smith, Emily Gleason, Sneha Kadiyala et al.
Published in JAMA Network on 20 March 2025
Abstract
Importance
International guidelines use cancer antigen (CA) 125 thresholds to recommend which patients with pelvic masses should undergo evaluation by gynaecologic 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. Generalised 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.
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Annual screening for ovarian cancer does not save lives — Large UK trial
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