CA-125 Early Dynamics to Predict Overall Survival in Women with Newly Diagnosed Advanced Ovarian Cancer Based on Meta-Analysis Data

SIMPLE SUMMARY: Cancer antigen 125 (CA-125) is a protein found at a high concentration in the blood of patients with specific types of cancer, mainly ovarian cancer. In 2004, the Gynecologic Cancer Intergroup (GCIG) proposed criteria defining response to treatment, as well as disease progression, based on the CA-125 concentration. Ever since, for the follow-up of ovarian cancer patients, the CA-125 concentration and/or CT-scans are used. This paper aims to compare different summaries of CA-125 evolution in the 3 to 6 months following treatment initiation in newly diagnosed advanced ovarian cancer and explore their prognostic capacity to predict overall survival. Based on individual patient data from the GCIG meta-analysis, we propose the most appropriate timeframe between follow-up and the prediction horizon in order to obtain robust, dynamic, individual predictions. ABSTRACT: (1) Background: Cancer antigen 125 (CA-125) is a protein produced by ovarian cancer cells that is used for patients’ monitoring. However, the best ways to analyze its decline and prognostic role are poorly quantified. (2) Methods: We leveraged individual patient data from the Gynecologic Cancer Intergroup (GCIG) meta-analysis (N = 5573) to compare different approaches summarizing the early trajectory of CA-125 before the prediction time (called the landmark time) at 3 or 6 months after treatment initiation in order to predict overall survival. These summaries included observed and estimated measures obtained by a linear mixed model (LMM). Their performances were evaluated by 10-fold cross-validation with the Brier score and the area under the ROC (AUC). (3) Results: The estimated value and the last observed value at 3 months were the best measures used to predict overall survival, with an AUC of 0.75 CI 95% [0.70; 0.80] at 24 and 36 months and 0.74 [0.69; 0.80] and 0.75 [0.69; 0.80] at 48 months, respectively, considering that CA-125 over 6 months did not improve the AUC, with 0.74 [0.68; 0.78] at 24 months and 0.71 [0.65; 0.76] at 36 and 48 months. (4) Conclusions: A 3-month surveillance provided reliable individual information on overall survival until 48 months for patients receiving first-line chemotherapy.