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This is the second-largest retrospective analysis addressing the controversy of whether adult rhabdomyosarcoma (RMS) should be treated with chemotherapy regimens adopted from pediatric RMS protocols or adult soft-tissue sarcoma protocols. A comprehensive database search identified 553 adults with primary non-metastatic RMS. Increasing age, intermediate-risk disease, no chemotherapy use, anthacycline-based and poor chemotherapy response were significant predictors of poor overall and progression-free survival. In contrast, combined cyclophosphamide-based, cyclophosphamide + anthracycline-based, or cyclophosphamide + ifosfamide + anthracycline-based regimens significantly improved outcomes. Intermediate-risk disease was a significant predictor of poor chemotherapy response. Overall survival of clinical group-III patients was significantly improved if they underwent delayed complete …