Received: 2 November 2017 | Accepted: 2 November 2017 DOI: 10.1002/jso.24933 REVIEW ARTICLE Systemic therapy in retroperitoneal sarcoma management Anastasia Constantinidou 1 | Robin L. Jones 2 1 Medical School University of Cyprus & The BoC Oncology Centre, Nicosia, Cyprus 2 The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, London, UK Correspondence Robin L. Jones, Sarcoma Unit, The Royal Marsden NHS Foundation Trust, The Institute of Cancer Research, Fulham Road, London SW3 6JJ, UK. Email: robin.jones4@nhs.net There is paucity of randomized controlled data on the role of systemic therapy in retroperitoneal sarcomas. The type of systemic therapy used is guided by the histological subtype. The majority of retroperitoneal sarcomas comprising lip- osarcomas and leiomyosarcomas are by and large chemotherapy insensitive. There is an urgent need for more efficacious systemic therapies in the management of early and advanced stage retroperitoneal sarcomas. KEYWORDS adjuvant, neoadjuvant, palliative, retroperitoneal sarcoma, systemic therapy 1 | INTRODUCTION Retroperitoneal sarcomas constitute a rare group of tumors with propensity to grow locally in the retroperitoneal space and less often to spread hematogenously. About 20-25% of retroperitoneal sarcomas will develop distant metastases resulting in a dismal median overall survival of 13 months. 1 The role of surgery for local control is well established in the management of these tumors 2 while the role of radiotherapy, particularly in the neoadjuvant setting, is currently being addressed in randomized controlled trials. 3 The role of systemic therapy, however, is yet to be defined although systemic therapy has been used both in the adjuvant/neoadjuvant setting as well as in the advanced/metastatic setting in the management of these tumors. The main purpose of systemic treatment in the neoadjuvant setting is to reduce the size of the primary tumor in order to facilitate R0 resection often reducing the need for extensive multiorgan resection. 4,5 In addition, neoadjuvant systemic therapy is used to control micrometastatic disease, to assess in vivo chemosensitivity and prevent prolonged administration of ineffective treatment. In the adjuvant setting, drug therapy is given to treat micrometastatic disease and ultimately reduce the risk of recurrence. 6 In the advanced setting the aim of systemic therapy is to reduce disease bulk, alleviate symptoms, and if possible prolong survival. The performance of prospective randomized controlled clinical trials has been limited by the small numbers of patients, and the heterogeneity of histological subtypes arising in the retroperitoneum. The majority of data on systemic therapy arise from retrospective studies or from a small number of prospective studies which however, lump various subtypes together to secure study power, and subsequently analyze outcomes separately according to different histology. The histological subtype is the most important factor influencing recurrence (both distant and local) and disease- specific death, as documented in large retrospective series of retroperitoneal sarcomas. 7 However, retroperitoneal sarcomas often demonstrate similar natural history characteristics, despite their differing histology; for example, they are usually asymptomatic and of a large size (>5 cm) by the time they are diagnosed. These factors influence their management in terms of type of therapy used (surgery, radiotherapy, systemic therapy) and the most appropriate timing for each therapy (neoadjuvant, adjuvant, palliative) taking into consideration each modality's toxicity profiles and quality of life patient reported outcomes, beyond the survival outcomes. The type of systemic therapy used is guided by the histological subtype of the retroperitoneal sarcoma. The majority of retroperito- neal sarcomas comprising liposarcomas and leiomyosarcomas are by and large chemotherapy insensitive, although some subtypes (ie, myxoid liposarcomas) have demonstrated higher sensitivity. 8 Other, less frequently occurring sarcoma subtypes including synovial sarcoma and Ewing's sarcoma may be more chemosensitive. In this article, we discuss the role of systemic therapy separately for each of the commonest subtypes with reference to the specific drugs used for each subtype, the treatment intent in each case and the available supporting evidence. Because of the rarity of retroperitoneal sarcoma and consequently the paucity of randomized controlled data, data on chemotherapy and biological therapy, are often extrapolated from studies on extremity sarcomas. 9 J Surg Oncol. 2018;117:87–92. wileyonlinelibrary.com/journal/jso © 2017 Wiley Periodicals, Inc. | 87