Differences in the Clinical Significance of CA125 for Detecting Progression among Histological Subtypes of Epithelial Ovarian Carcinoma

Serum cancer antigen 125 (CA125) is the standard tool for surveillance of patients with epithelial ovarian carcinoma (OC). However, its utility may vary by histological subtype. The present study included patients with epithelial OC who completed primary therapy (surgery and chemotherapy) at the National Defense Medical College Hospital (Tokorozawa, Japan) between January 2006 and December 2022, achieved complete or partial response, and had a post-treatment CA125 level of <35 U/ml. Recurrence was defined using the Response Evaluation Criteria in Solid Tumors criteria via computed tomography (CT) imaging. Surveillance included quarterly CA125 testing for 5 years, and semiannual CT in year 1 followed by annual CT. All patients were classified into Group A, which included clear cell carcinoma and mucinous carcinoma, or Group B, which included high-grade serous carcinoma and other subtypes. Among 243 patients, there were 85 in Group A and 158 in Group B. First, the diagnostic performance of the standard CA125 cutoff (≥35 U/ml) for detecting recurrence was evaluated. The sensitivity was 28.6% in Group A and 81.8% in Group B; and the specificity was 98.4% in Group A and 98.8% in Group B. Second, because the sensitivity in Group A was very low, the CA125 ratio and a combined model (defined as CA125 ≥35 U/ml or CA125 ratio ≥1.5) were introduced. The CA125 ratio was defined as the maximum CA125 value measured at CT surveillance divided by the CA125 value measured just after the initial treatment for patients with CA125 <35 U/ml. The sensitivity was 66.7% in Group A and 93.5% in Group B; and the specificity was 84.1% in Group A and 86.4% in Group B. In conclusion, the utility of CA125 for the detection of recurrence differs substantially between histological subtypes, highlighting the need for histological subtype-specific surveillance strategies in epithelial OC.