Prognostic value of circulating tumor cells' reduction in patients with extensive small-cell lung cancer

tObjectives: Circulating tumor cells (CTCs) have been hypothesized to be a prognostic factor in small-celllung cancer (SCLC), and different cutoffs have been proposed to identify patients at high risk. We assessedthe prognostic value of CTCs in patients with extensive SCLC.Materials and methods: CTCs were assessed with the CellSearch system in 60 extensive SCLC patients. CTCcount at baseline or after one cycle of chemotherapy (cycle-1) or as change after chemotherapy wereanalyzed separately. Primary outcome was overall survival. The accuracy of prognostic role was assessedby Harrell’s c-index. “Optimal” cutoffs were derived by bootstrap resampling to reduce the overfittingbias; accuracy improvement was estimated by calculating the difference of c-indexes of models includingclinical variables with or without CTCs.Results: CTCs were identified in 90% (54/60) of patients at baseline, in which CTC count ranged from0 to 24,281. CTC count was strongly associated with the number of organs involved. The prognosticaccuracy was only marginally increased by the addition to clinical information of “optimal” CTC cutoffs atbaseline and after cycle-1. Conversely, a reduction of CTC count higher than 89% following chemotherapysignificantly improved prognostic accuracy (bootstrap p-value = 0.009) and was associated with a lowerrisk of death (HR 0.24, 95% CI 0.09–0.61). When previously proposed cutoffs were applied to our cohort,they showed only marginal improvement of the prognostic accuracy.Conclusion: CTCs have useful prognostic role in extensive SCLC, but only the change of CTC count afterthe first cycle of chemotherapy provides clinically relevant information. Previously reported CTC cutoffswere not prognostic in our cohort of patients.