PURPOSE: This study aimed to evaluate the relationship between CTC levels and prognosis in patients with smallcell lung cancer (SCLC).PATIENTS AND METHODS: In total, 51 consecutive patients with newly diagnosed SCLC, starting chemotherapy or chemoradiotherapy, were prospectively enrolled (30 patients in the training set, 21 in the validation set).Blood samples were drawn at baseline, after chemotherapy, and at relapse.CTCs were isolated using the CellSearch System (Veridex LLC).RESULTS: Two or more baseline-CTCs were detected in 35 patients, 68.6% (95% CI, 55.0-79.7).The Cox proportionalhazards ratio (HR) signifying the difference between the unfavorable (above threshold) and favorable (below threshold) groups was maximized at a threshold of 8 CTCs, with a HR of 9.54 (95%CI, 2.18-68.05).The favorable group showed better survival than the unfavorable group in the validation set (p =0.0320, by log-rank test).Patients with <8 CTCs post-treatment or at relapse also lived longer from the time of blood collection than those with ≥ 8 CTCs (p =0.0282 and 0.0006).Patients whose CTC level remained <8 cells after treatment (defined as reference) showed better survival than those whose CTC level converted from ≥ 8 to <8 cells, with a HR of 7.46 (1.96-30.42), or whose CTC level remained or converted to ≥ 8 cells after treatment, with a HR of 4.18 (1.04-17.46).CONCLUSIONS: CTCs were highly detectable in SCLC and lower CTC levels were strongly associated with better survival.Consistently favorable CTC levels were associated with better outcomes than unfavorable pre or post-treatment CTC levels.