The Impact of Chemotherapy on Survival of Patients with Extremity and Trunk Wall Soft Tissue Sarcoma: Revisiting the Results of the EORTC-STBSG 62931 Randomised Trial Using Sarculator, a Validated Nomogram-Based Risk Assessment Tool

Abstract

BACKGROUND: To determine whether patients with high-risk soft tissue sarcoma (STS), as identified using the nomogram Sarculator, benefitted from adjuvant chemotherapy in the EORTC-STBSG 62931 randomised controlled trial (RCT) which failed to detect an impact for adjuvant doxorubicin plus ifosfamide (Adj) over observation (Obs). METHODS: A retrospective analysis of the EORTC-STBSG 62931 RCT was performed on individual patient data of study participants with extremity and trunk wall STS (N=290/351). 10-year predicted probability of overall survival (pr-OS) was calculated using the prognostic nomogram Sarculator. Patients were grouped in three categories of predicted pr-OS: high (pr-OS > 66%), intermediate (51< pr-OS ≤ 66), and low (pr-OS ≤ 51%). OS and disease-free survival (DFS) were calculated at the study median follow-up (8-year). FINDINGS: Nomogram pr-OS were dispersed (median 72%, IQR 57-83%) and had prognostic value for OS and DFS (Log-Rank test: P<0·001). 170 patients had high pr-OS (58·6%, 90 Obs/80 Adj), 68 intermediate (23·5%, 34 Obs/34 Adj) and 52 low (17·9%, 24 Obs/28 Adj). Adjuvant chemotherapy halved the risk of recurrence (HR=0·46, 95%CI 0·24-0·89) and death (HR=0·46, 95%CI 0·23-0·94) in the low pr-OS category, while no effect was detected in the intermediate and high pr-OS categories. In order to strengthen these findings, study participants with predicted pr-OS<60% were combined (N=80, 27·6%, 39 Obs/41 Adj) and a significant benefit in terms of DFS (HR=0·49, 95%CI 0·28-0·85) and OS (HR=0·50, 95%CI 0·30-0·90) was detected. INTERPRETATION: Patients of the EORTC-STBSG 62931 RCT with extremity and trunk wall STS and a low predicted pr-OS (i.e., high-risk patients) had a better outcome when treated with adjuvant chemotherapy. This may help reconcile the somewhat disparate results of published clinical studies on adjuvant/neoadjuvant chemotherapy in high/risk STS. Funding Statement: This was an academic non-funded study. The EORTC-STBSG 62931 trial was funded by European Organisation for Research and Treatment of Cancer (EORTC) and Rhone-Poulenc-Rorer. Declaration of Interests: The authors declare they have no conflicts of interest. Ethics Approval Statement: The protocol of the EORTC-STBSG 62931study was approved by the EORTC Protocol Review Committee and institutional review boards. The patients gave informed consent according to applicable laws in all participating countries. The current study was approved by EORTC through the ‘Request for data platform’.