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Optimal treatment sequences for metastatic castration-resistant prostate cancer are unknown. This retrospective study assessed outcomes in patients with metastatic castration-resistant prostate cancer receiving second-line taxane chemotherapy versus second-line androgen receptor-targeted therapy (ART), after failure of first-line ART, in a real-world setting. In patients who have previously recieved ART, second-line taxane chemotherapy, versus alternative ART, may be associated with improved outcomes, particularly among patients with a worse disease prognosis.