Synovial sarcoma: characteristics, challenges, and evolving therapeutic strategies

Abstract

Synovial sarcoma (SS) is a rare and aggressive disease that accounts for 5%-10% of all soft tissue sarcomas. Although it can occur at any age, it typically affects younger adults and children, with a peak incidence in the fourth decade of life. In >95% of cases, the oncogenic driver is a translocation between chromosomes X and 18 that leads to the formation of the SS18::SSX fusion oncogenes. Early and accurate diagnosis is often a challenge; optimal outcomes are achieved by referral to a specialist center for diagnosis and management by a multidisciplinary team as soon as SS is suspected. Surgery with or without radiotherapy and/or chemotherapy can be effective in localized disease, especially in children. However, the prognosis in the advanced stages is poor, with treatment strategies that have relied heavily on traditional cytotoxic chemotherapies. Therefore, there is an unmet need for novel effective management strategies for advanced disease. An improved understanding of disease pathology and its molecular basis has paved the way for novel targeted agents and immunotherapies that are being investigated in clinical trials. This review provides an overview of the epidemiology and characteristics of SS in children and adults, as well as the patient journey from diagnosis to treatment. Current and future management strategies, focusing particularly on the potential of immunotherapies to improve clinical outcomes, are also summarized.

Keywords: NY-ESO-1; cellular therapy; chemotherapy; immunotherapy; synovial sarcoma; targeted therapy.

Figure 1

Initial patient pathway from presentation to diagnosis and early disease management in adult and pediatric patients with SS^a,. Adj, adjuvant; CT, computerized tomography; FNCLCC, Fédération Nationale des Centres de Lutte Contre Le Cancer; RT, radiotherapy; STS, soft tissue sarcoma. ^aAccording to tumor size. ^bSubject to histology and site. ^cAdapted from Figures 1, 2, 3, and 4 of ‘Soft tissue and visceral sarcomas: ESMO–EURACAN–GENTURIS Clinical Practice Guidelines for diagnosis, treatment and follow-up’ published by Gronchi et al, in Annals of Oncology (2017). ^dAccording to recent reports, there is an ongoing debate on whether patients with SS can be grade 1. According to the FNCLCC grading system, synovial differentiation should be scored at 3, with a mitotic HMF score of >1 and a necrosis of >0, corresponding to grade 2 disease.