CA125 Kinetics as a Potential Biomarker for Peritoneal Metastasis Progression following Taxane-Plus-Ramucirumab Administration in Patients with Advanced Gastric Cancer

Simple Summary Patients with advanced gastric cancer (AGC) often discontinue treatment when peritoneal metastases progress, particularly during second- or third-line chemotherapy. To prevent serious complications like bowel obstruction or increased ascites burden, it is crucial to identify predictors of peritoneal metastases before they occur. In this study, serum carbohydrate antigen 125 (CA125) concentrations were found to be associated with increased ascites burden in patients with AGC and served as a prognostic factor. Moreover, CA125 kinetics, measured at a median interval of 28 days after initiating taxane-plus-ramucirumab treatment, were found to be associated with the ascites response. Furthermore, an increase in CA125 concentration exceeding 0.0067% per day, as determined by receiver operating characteristic curve analysis, predicted the progression of peritoneal metastases. Thus, monitoring CA125 kinetics is vital for predicting the progression of peritoneal metastases and can help determine the optimal timing for subsequent chemotherapy.Abstract Currently, no established marker exists for predicting peritoneal metastasis progression during chemotherapy, although they are major interruptive factors in sequential chemotherapy in patients with advanced gastric cancer (AGC). This multicenter retrospective study was conducted from June 2015 to July 2019, analyzing 73 patients with AGC who underwent taxane-plus-ramucirumab (TAX/RAM) therapy and had their serum carbohydrate antigen 125 (CA125) concentrations measured. Of 31 patients with elevated CA125 levels above a cutoff of 35 U/mL, 25 (80.6%) had peritoneal metastasis. The CA125 concentrations before TAX/RAM treatment were associated with ascites burden. The overall survival was significantly shorter in the CA125-elevated group. CA125 kinetics, measured at a median of 28 days after chemotherapy, were associated with the ascites response (complete or partial response: -1.86%/day; stable disease: 0.28%/day; progressive disease: 2.33%/day). Progression-free survival in the CA125-increased group, defined by an increase of 0.0067%/day using receiver operating characteristic curve analysis, was significantly poorer among patients with peritoneal metastases. In conclusion, this study highlights that CA125 kinetics can serve as an early predictor for the progression of peritoneal metastasis during TAX/RAM treatment.