• In patients with metastatic or unresectable soft tissue and bone sarcoma of extremities and pelvis, survival is generally poor. The aim of the current systematic review was to analyse recent publications on treatment approaches in patients with inoperable and/or metastatic sarcoma.

• Original articles published between 1st January 2011 and 2nd May 2020, using the search terms ‘unresectable sarcoma’, ‘inoperability AND sarcoma’, ‘inoperab* AND sarcoma’, and ‘treatment AND unresectable AND sarcoma’ in PubMed, were potentially eligible. Out of the 839 initial articles (containing 274 duplicates) obtained and 23 further articles identified by cross-reference checking, 588 were screened, of which 447 articles were removed not meeting the inclusion criteria. A further 54 articles were excluded following full-text assessment, resulting in 87 articles finally being analysed.

• Of the 87 articles, 38 were retrospective (43.7%), two prospective (2.3%), six phase I or I/II trials (6.9%), 22 phase II non-randomized trials (27.6%), nine phase II randomized trials (10.3%) and eight phase III randomized trials (9.2%). Besides radio/particle therapy, isolated limb perfusion and conventional chemotherapy, novel therapeutic approaches, including immune checkpoint inhibitors and tyrosine kinase inhibitors were also identified, with partially very promising effects in advanced sarcomas.

• Management of inoperable, advanced or metastatic sarcomas of the pelvis and extremities remains challenging, with the optimal treatment to be defined individually. Besides conventional chemotherapy, some novel therapeutic approaches have promising effects in both bone and soft tissue subtypes. Considering that only a small proportion of studies were randomized, the clinical evidence currently remains moderate and thus calls for further large, randomized clinical trials.

Cite this article: EFORT Open Rev 2020;5:799-814. DOI: 10.1302/2058-5241.5.200069

• The relatively low incidence and often atypical clinical presentation of soft-tissue sarcomas (STS) impedes early and adequate diagnosis. Patients may report on recently enlarged soft-tissue swellings, infrequently complain of painful lesions, or even have no symptoms at all.

• A thorough diagnostic work-up is essential in order to distinguish between benign soft-tissue tumours and STSs. Patient history, clinical features and radiological findings all help in assessing the underlying pathology. ‘Worrying’ features such as recent increase in size, deep location relative to the fascia, a tumour exceeding 4 cm in size, and invasive growth patterns seen on imaging should prompt verification by biopsy.

• Even though acquisition of biopsy material may be incomplete, one should bear in mind some essential rules. Regardless of the biopsy technique applied, the most direct route to the lump in question should be identified, contamination of adjacent structures should be avoided and a sufficient amount of tissue acquired.

• Treatment of STS is best planned by a multidisciplinary team, involving experts from various medical specialities. The benchmark therapy consists of en bloc resection of the tumour, covered by a safety margin of healthy tissue. Depending on tumour histology, grade, local extent and anatomical stage, radiotherapy, chemotherapy and isolated hyperthermic limb perfusion may be employed.

• Due to the complexity of treatment, any soft-tissue swelling suspected of malignancy is best referred directly to a sarcoma centre, where therapeutic management is carefully planned by an experienced multidisciplinary team.

Cite this article: EFORT Open Rev 2017;2:421-431. DOI: 10.1302/2058-5241.2.170005