Serum CA125 levels in the context of ProMisE molecular classification provides pre-operative prognostic information that can direct endometrial cancer management.

OBJECTIVE

Previous research suggests serum CA125 reflects extra-uterine disease in patients with endometrial carcinoma (EC). Our objective was to determine if CA125 can identify patients with extra-uterine and/or nodal metastases, the association of this biomarker with EC molecular subtype, and to explore an optimal cutoff in this context.

METHODS

We assessed the association of CA125 levels with clinicopathologic and outcomes data on a cohort of 1107 molecularly classified EC.

RESULTS

Abnormal CA125 (>35kU/L) was associated with higher stage and lymph node metastases (LNM) in all EC and in each molecular subtype on univariate (p < 0.01) and multivariate (p < 0.05) analyses. POLEmut had the lowest median CA125 level and proportion of CA125 abnormal patients, and p53abn the highest proportion (p < 0.001). CA125 > 35 kU/L had a sensitivity of 0.82, specificity 0.53, positive-predictive-value 0.92, and negative-predictive-value 0.31 for LNM, with similar values for stage>I. CA125 > 35 kU/L was associated with worse overall (OS), disease-specific (DSS), and progression-free survival (PFS) in all EC, p53abn (OS, DSS, PFS), NSMP (OS, DSS), and MMRd (OS, DSS) subtypes. CA125 > 35 kU/L demonstrated a relative risk (RR) of 2.50 with presence of stage III/IV disease (p < 0.001) and RR 18.4 for the presence of synchronous endometrial and ovarian carcinomas (SEOC)/co-existing adnexal malignancies (CAM) (p < 0.001). An exploratory cut point, optimized for correlation with DSS (CA125 > 24 kU/L) show similar association with clinical parameters and survival outcome.

CONCLUSIONS

CA125 levels are associated with molecular subtype, stage>I disease, and SEOC/CAM. CA125 remains a useful clinical tool in the triage of EC in the era of molecular classification.