Neoadjuvant Treatment of Locally Advanced Soft Tissue Sarcoma of the Limbs: Which Treatment to Choose?

Soft tissue sarcomas form a heterogeneous group of malignant neoplasms arising in the mesenchymal connective tissues. Treatment concepts of preoperative therapy differ significantly among centers. This review aims to elucidate the rationale of different regimens and analyze their potentials as well as weaknesses. Learning Objectives After completing this course, the reader will be able to: Describe and weigh the available treatment options for the neoadjuvant therapy of soft tissue sarcoma of the limbs. Discuss the positive effects of preoperative treatment concepts on resection margins. Balance the adverse effects of pretreatment on subsequent operative morbidity. Interpret the weaknesses of currently available study results. Access and take the CME test online and receive 1 AMA PRA Category 1 Credit™ at CME.TheOncologist.com Soft tissue sarcomas (STSs) form a heterogeneous group of malignant neoplasms arising in the mesenchymal connective tissues. They can develop at any anatomic site but 60% occur in the extremities. Initially, treatment of STS relied solely on excision. In the 1970s, Enneking et al. developed the concept of compartmental resection to reduce the local failure rate. Later, Rosenberg et al. demonstrated, in a randomized study, that there was no difference in local tumor control and disease‐free survival (DFS) in patients treated with amputation versus limb‐saving surgery followed by 50–70 Gy external‐beam radiotherapy (EBRT). A considerable proportion of patients present with locally advanced tumors as a primary or recurrent disease and cannot be resected with adequate clearance margins. These patients are threatened with amputation for complete tumor removal. Improvements in surgical techniques, such as microvascular muscle flaps, allow for the avoidance of limb loss in the majority of cases. However, the use of frozen sections to determine intraoperatively whether clear margins have been achieved is limited by the multiplanarity of resection specimens. Thus, local failure rates are 15%–25%, and preoperative measures to sterilize the invasive margin of sarcomas have been explored. High‐dose preoperative EBRT for high‐grade STS was developed, and its combination with intra‐arterial or i.v. chemotherapy was reported to be effective. Recently, systemic chemotherapy combined with deep wave hyperthermia was shown to result in a longer DFS time in a large, randomized, phase III study. Treatment concepts differ significantly among centers and a