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The standard treatment of high-risk localized extremity and trunk soft-tissue sarcoma is wide local excision and radiation therapy, which can be delivered pre- or postoperatively. Improved care for sarcoma patients at expert centres with multidisciplinary tumour boards, specialized pathologists, surgeons, radio-oncologists, and medical oncologists, according to national or international guidelines, has improved outcomes. Yet, a substantial number of patients will experience disease recurrence with metastatic spread and ultimately die from their disease. In many solid tumours neo/adjuvant chemotherapy has become an accepted standard treatment, whereas in soft-tissue sarcoma discussions on the use of cytotoxic therapy in localized and resectable disease are ongoing. Some centres demonstrated the feasibility and now treat with concomitant neoadjuvant chemoradiotherapy as standard. Others argue that treatments should be given in the order of the accompanying evidence (surgery → radiotherapy → chemotherapy), which does not take biology of the disease into account and probably attempts to simplify complex decision making processes. It is important to enhance our ability to identify patients at highest risk of recurrence, and to generate data and develop tools to predict which patients will benefit from neo/adjuvant systemic therapy most.