Objective:We investigated the correlation between the number of circulating tumor cells (CTCs) and whole-body metabolic tumor volume (WBMTV) measured by 18F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT).The aim was to evaluate the value of the incorporation of CTC number and WBMTV in the prognostic prediction of stage Ⅲ small-cell lung cancer (SCLC).Methods:One hundred and twenty-nine patents were enrolled in this study.All patients were treated with four cycles of a platinum-based regimen and concurrent chest irradiation,followed by prophylactic cranial irradiation.Blood samples for CTC analysis were obtained from 112 patients before the initiation of chemotherapy (as a baseline),after cycle 1 and after cycle 4.CTCs were measured using the CELLSEARCH(R) system.The patients underwent pretreatment FDG PET/CT WBMTV,which included all malignant lesions.The Spearman rank test was used to determine the correlation among CTC counts,WBMTV and disease stage.Overall survival (OS) and progression-free survival (PFS) curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank test.Results:The number of CTCs at baseline did not correlate with WBMTV before the initiation of therapy (P=0.241).The number of CTCs at baseline and the WBMTV before the initiation of therapy were independent relevant factors for PFS and OS.The subgroup analysis (Group A:CTC count ＞19.5 and a WBMTV ＞266.5 cm3;Group B:CTC count ＞19.5 and a WBMTV≤266.5 cm3;Group C:CTC count ≤19.5 and a WBMTV ＞266.5 cm3;Group D:CTC count ≤19.5 and a WBMTV ≤266.5 cm3) showed that the differences were statistically significant in the median PFS (Group A vs.D,P＜0.001;Group B vs.D,P=0.018;Group C vs.D,P=0.029) and in the median OS (Group A vs.D,P＜0.001;Group B vs.D,P=0.012).Conclusions:CTC number and WBMTV are related to progression and death in patients with SCLC.The incorporation of CTC number and WBMTV scans can provide a detailed prognostic prediction for SCLC.