The EpSSG NRSTS 2005 study: a landmark for paediatric non-rhabdomyosarcoma soft tissue sarcomas

01 July 2021

Paediatric non-rhabdomyosarcoma soft tissue sarcomas: the prospective NRSTS 2005 study by the European Pediatric Soft Tissue Sarcoma Study Group (EpSSG)

The EpSSG NRSTS 2005 protocol represents the first European-based prospective protocol specifically dedicated to children and adolescents with NRSTS.

In the last years, the EpSSG has reported the analyses of some specific histological subgroups registered in the protocol. This manuscript reported the treatment results of the whole series of patients enrolled in the two prospective non-randomized studies dedicated to localised synovial sarcoma and adult-type NRSTS (between May 2005 and Dec 2016).

Overall, 569 patients younger than 21 years (206 synovial sarcoma and 363 adult-type NRSTS) were selected for the analysis out of 1321 cases registered in the NRSTS 2005 database.

The EpSSG analysis helped to define the risk-adapted standard of care for this patient population. For the whole cohort, 5-year EFS and OS were 74% and 84%. Survival rates changed according to the treatment groups. The outcome was excellent for patients in the “surgery alone” group (n=250) (5-year EFS 91%, OS 98%), suggesting that adjuvant treatments can be safely omitted in the low-risk population to reduce both short-term and long-term treatment-related morbidity and mortality. Five-year EFS and OS were 75% and 88% in the “adjuvant radiotherapy” group (n=17), 65% and 75% in the “adjuvant chemotherapy” group (with or without radiotherapy) (n=93), 56% and 70% in the “neoadjuvant chemotherapy” group (with or without radiotherapy) (n=209). Improving the outcome for patients with high-risk cases remains a major clinical challenge: although prognosis for grossly resected NRSTS was generally good, patients with high-grade and large tumours are at high risk of metastatic spread. For unresected cases, our study showed favourable results by comparison with previous series (neoadjuvant ifosfamide plus doxorubicin chemotherapy seemed to improve the resectability rate compared with previous studies).

A major problem is whether these tumours should be studied and treated as one group, or, given their heterogeneity, by histological or molecular subgroups. Although it would be best to study NRSTS as single entities, this remains extremely difficult because of their rarity. Therefore, pooling resources and increasing international collaborative research, especially with the adult sarcoma community, to develop all-age studies dedicated to soft tissue sarcomas will be important. New comprehensive strategies might also lead to the identification of new targets for novel therapies, which are much needed for those patients with NRSTS who have an unfavourable prognosis.
Author: Andrea Ferrari, Max M van Noesel, Daniel Orbach and EpSSG colleagues