Sensitivity of CA-125 by ovarian cancer histology.

e17557 Background: Women with ovarian cancer may have subtle symptoms, delaying diagnosis to late stage. Guidelines recommend use of cancer antigen 125 (CA-125) in the work up of suspected ovarian cancer, especially for which patients need referral to gynecologic oncology. Yet “normal” CA-125 thresholds of 35 units/mL in practice were developed in 1980s in a homogenous group of women with different distribution of ovarian cancer histologies than current. Our objective was to compare the sensitivity of different CA-125 thresholds across ovarian cancer histologies. Methods: We identified patients with newly-diagnosed ovarian cancer from the Penn Medicine Cancer Registry, 2009-2023 (n=2,785) supplemented with patients identified by ICD codes, 2020-2023 (n=1,342). CA-125 values obtained within 60 days of diagnosis were abstracted from the electronic health record. We examined the sensitivity of current CA-125 thresholds by histology. Results: Among 1670 patients with ovarian cancer and CA-125 at diagnosis, the median CA-125 at diagnosis was 255.0 (interquartile range 49.0-955.0) in epithelial tumors compared to 41.0 (IQR 26.0-264.8) for germ cell and 23.2 (IQR 16.0-53.5) for sex cord stromal tumors. Within epithelial tumor types, CA-125 ranged from 31.2 (IQR 21.0,92.0) in mucinous tumors, 34.0 (IQR 21.0,104.0) in borderline tumors, 193.0 (IQR 35.0,807.6) in low-grade serous to 466.0 (IQR 112.0,1328.0) in high-grade serous tumors. At diagnosis, 50% of patients with ovarian cancer had CA-125 <35 units/mL, including 20% of epithelial tumors. Lowering CA-125 threshold to 15 units/mL improved sensitivity to 92%. Conclusions: Current thresholds of abnormal CA-125, used for gynecologic oncology referral, miss up to half of individuals with ovarian cancer. Sensitivity is lowest for mucinous and borderline tumors that are increasingly common. Updated thresholds are needed to avoid delays in diagnosis, and strengthen the potential for cure, in ovarian cancer.