Prognostic value of circulating tumor cells associated with white blood cells in solid cancer: A systematic review and meta-analysis of 1471 patients with solid tumors

Background: The clinical relevance of circulating tumor cell-white blood cell (CTC-WBC) clusters in cancer prognosis is a subject of ongoing debate. This study aims to unravel their contentious predictive value for patient outcomes. Methods We conducted a comprehensive literature search of PubMed, Embase, and Cochrane Library up to December 2022. Eligible studies that reported survival outcomes and examined the presence of CTC-WBC clusters in solid tumor patients were included. Hazard ratios(HR) were pooled to assess the association between CTC-WBC clusters and overall survival (OS), as well as progression-free survival(PFS)/disease-free survival(DFS)/metastasis-free survival(MFS)/recurrence-free survival(RFS). Subgroup analyses were performed based on sampling time, treatment method, detection method, detection system, and cancer type. Results A total of 1471 patients from 10 studies were included in this meta-analysis. The presence of CTC-WBCs was assessed as a prognostic factor for overall survival and PFS /DFS /MFS /RFS. The pooled analysis demonstrated that the presence of CTC-WBC clusters was significantly associated with worse OS (HR = 2.44, 95% CI: 1.74–3.40, P < 0.001) and PFS/DFS/MFS/RFS (HR = 1.83, 95% CI: 1.49–2.24, P < 0.001). Subgroup analyses based on sampling time, treatment method, detection method, detection system, and cancer type consistently supported these findings. Further analyses indicated that CTC-WBC clusters were associated with larger tumor size (OR = 2.65, 95% CI: 1.58–4.44, P = 0.0002) and higher alpha-fetoprotein levels (OR = 2.52, 95% CI: 1.50–4.22, P = 0.0004) in hepatocellular carcinoma. However, no significant association was found between CTC-WBC clusters and TNM stage, depth of tumor invasion, or lymph node metastasis in the overall analysis. Conclusions CTC-WBC clusters are negative predictors for OS and PFS /DFS /MFS /RFS in patients with solid tumors. Monitoring CTC-WBC levels may provide valuable information for predicting disease progression and guiding treatment decisions.