Tian X, Ge D, Zhang F, et al. - For metastatic relapsed cervical cancer (MRCC), there are currently limited and inefficient treatment options as well as there exist no reliable indicators to guide therapeutic selection. In this study, deep sequencing analyses were conducted targeting 322 cancer‐related genes in plasma cell‐free DNA and matched white blood cells in 173 serial blood samples from 82 locally advanced CC (LACC) or MRCC patients and when possible, during treatment. In the MRCC samples, five notable nonsynonymous mutant genes (PIK3CA, BRAF, GNA11, FBXW7, and CDH1) as the metastatic relapse significantly mutated (MSG) genes were identified. Significantly shorter progression‐free survival (PFS) and overall survival (OS) were reported for MRCC patients with any detectable MSG mutations vs those without detectable MSG mutations. In addition, analyses of matched pre‐ and post‐ chemotherapy plasma indicated partial remission (PR) and stable disease (SD) in significant correlation with a decrease in the number of MSG mutations after chemotherapy. Among the patients included in the longitudinal tracking ctDNA analysis, there was a rise in MSG mutations earlier in response to disease progression than radiological imaging. Per these findings, longitudinal monitoring with ctDNA in liquid biopsy samples is valuable for both predictive and prognostic information during treatment.