A multicenter retrospective cohort study evaluating the clinical significance of CA125 in later line of patients with metastatic colorectal cancer.
Authors: Ito Ken , Ando Takayuki , Ueda Akira , Motoo Iori , Kito Yosuke , Ishiguro Atsushi , Tanaka Kazunari , Hosokawa Ayumu , Nakashima Koji , Wakabayashi Toshiki , Muto Osamu , Dazai Masayoshi , Yoshida Taichi , Yamamura Takahiro , Harada Kazuaki , Kawamoto Yasuyuki , Sakamoto Naoya , Komatsu Yoshito , Yuki Satoshi 
Published: January 2023

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Background: The peritoneal dissemination is one of the metastatic forms of gastrointestinal cancer and has a poor prognosis. It has been reported that the presence of CA125 in mesothelial cells lining the peritoneum is involved in the elevation of CA125 due to peritoneal dissemination and inflammation of cancerous ascites, and CA125 may be a useful predictor of peritoneal dissemination in gastrointestinal cancer. It has also been reported that CA125 correlates with ascites volume and prognosis. However, there are no reports evaluating the clinical significance of CA125 in the later line of metastatic colorectal cancer (mCRC). Therefore, we conducted a multicenter retrospective study. Methods: We retrospectively analyzed the clinical data of 121 patients who received trifluridine/tipiracil (FTD/TPI) or Regorafenib from January 2012 to May 2018 in 10 centers and had the result of serum CA125 just before the treatment. Patients who had received either FTD/TPI or Regorafenib were excluded. In this study, the levels of ascites were classified as follows: "none" as undetectable by computed tomography scanning, "mild" as confined to the pelvic cavity or upper abdomen, "severe" as continuous from the pelvic cavity to the upper abdomen, and "moderate" as between "mild" and "severe". RECIST ver.1.1 was used for analysis of tumor response. Survival analyses were performed with Kaplan-Meier method, log-rank test and Cox proportional hazards model. Results: There were 75 patients in the baseline CA125 normal group (group N) and 46 patients in the high group (group H). ECOG PS tended to be worse in group H than in group N (ECOG PS (0/1/2) 26/43/6 and 9/28/9 in N and H groups, p=0.076). There were significantly more patients with ascites in group H than in group N (Yes/No 7/68 and 26/20 in N and H groups, p<0.001). Furthermore, ALP, CRP, CA19-9 and NLR were significantly higher, and Alb was significantly lower in group H than in group N. Baseline CA125 correlated with baseline ascites volume (p<0.001). PFS and OS were significantly shorter in group H compared to group N (PFS; 1.9 vs. 3.0 months; HR 1.576 [95%CI 1.081-2.299]; p=0.016, OS; 4.1 vs. 11.0 months; HR 2.418 [95%CI 1.634-3.576]; p<0.001). The rate of change for CA125 was significantly higher in patients with progressive disease on first evaluation CT compared to patients with disease control (p=0.002), and PFS and OS were significantly shorter in the increased CA125 group measured first after treatment than in the non-increased CA125 group (PFS; 1.9 vs. 4.6 months; HR 3.104 [95%CI, 2.004-4.809]; p<0.001, OS; 5.9 vs. 13.0 months; HR 2.199 [95%CI, 1.474-3.282]; p<0.001). Conclusions: In this retrospective analysis, baseline CA125 correlated with ascites volume in later line treatment of patients with mCRC, suggesting that increased CA125 may be a predictive and prognostic factor. Clinical trial information: UMIN000040059 .