From collision to conversion, the molecular renaissance of uterine carcinosarcoma in the era of antibody-drug conjugates: a scoping review

INTRODUCTION: Uterine carcinosarcoma is a rare aggressive uterine malignancy increasingly regarded as a metaplastic endometrial carcinoma rather than a true collision tumor. Its marked molecular heterogeneity has important implications for classification, prognosis, and treatment. AREAS COVERED: This scoping review summarizes histogenesis and molecular landscape of uterine carcinosarcoma and evaluates clinical evidence for immunotherapy, targeted therapies, and antibody-drug conjugates. PubMed/MEDLINE, Scopus, and ClinicalTrials.gov were searched from inception to 29 July 2026, supplemented by citation searching and targeted searches. Most tumors exhibit a copy-number-high genomic profile or are classified as p53-abnormal, whereas mismatch repair-deficient and POLE-mutated tumors represent smaller but clinically relevant subsets. The clinical evidence base for immunotherapy remains extrapolated from broader endometrial cancer trials, although direct prospective evidence from small uterine carcinosarcoma cohorts is emerging. Earlier unselected targeted approaches showed modest activity, whereas biomarker-selected strategies, particularly HER2-directed trastuzumab deruxtecan, have produced encouraging signals. EXPERT OPINION: Molecular profiling is likely to refine treatment selection and sequencing, especially in advanced or recurrent disease. However, progress depends on standardized biomarker assessment, international multicenter trials, and mandatory carcinosarcoma-specific outcome reporting. Surgery and platinum-based chemotherapy are likely to remain the therapeutic backbone, while future progress will depend on integrating validated biomarkers into disease-specific treatment algorithms.