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Objectives: In patients with metastatic castration-resistant prostate cancer (mCRPC), the finding of less than five circulating tumor cells (CTCs)/7.5 mL blood before start of cytotoxic treatment or shortly thereafter indicates prolonged survival. In this descriptive pilot study, we investigated whether this association depends on the sequence of the therapeutic attempts. Patients and methods: CTCs were determined in 41 mCRPC patients before and 2-3 months after starting first-line treatment with docetaxel (group 1) or second-line treatment with either radium-223 (group 2) or placebo/best supportive care (group 3). A "favorable" CTC count was defined as,5 CTC/7.5 mL blood. The results were related to overall survival. Pretreatment, six of ten men in group 1, three of 19 in group 2, and three of 12 patients Results: in group 3 had a favorable CTC count, leading to a significant difference between first- and second-line therapy (P=0.04). Decrease of pretreatment elevated CTCs to a favorable CTC count was significantly more often observed in patients on first-line therapy (three of four patients) than on second-line treatment (two of 26 men) (P=0.03). A favorable CTC count before or shortly after treatment start was observed in nine of ten patients on first-line and in eight of 31 men on second-line therapy (P=0.01). A favorable CTC count pretreatment or 2-3 months after therapy start was associated with beneficial overall survival in the three groups combined and in each group analyzed separately. Conclusion: In mCRPC, a favorable CTC count before or 2-3 months after start of therapy is associated with length of overall survival, though such favorable CTC counts are observed significantly less often in patients on second- than on first-line therapy. [ABSTRACT FROM AUTHOR]