STRASS (EORTC 62092): A phase III randomized study of preoperative radiotherapy plus surgery versus surgery alone for patients with retroperitoneal sarcoma.

Abstract

11001 Background: The predominant pattern of failure of retroperitoneal sarcoma (RPS), frequently associated with subsequent death, is locoregional recurrence. Unlike in limbs, the efficacy of radiotherapy (RT) combined with surgery is not established. Methods: STRASS is a randomized, multicentre, international trial. Eligible patients had histologically-proven localized primary RPS, operable and suitable for radiotherapy. Patients were randomized 1:1 to preoperative RT (3D-CRT or IMRT) 50.4 Gy followed by surgery (RT/S group) or surgery alone (S group), stratified by hospital and performance status (0-1 vs 2). Primary endpoint is abdominal recurrence-free survival (ARFS; local relapse after complete resection, peritoneal sarcomatosis, R2 surgery, progressive disease during RT or unresectable disease). IDMC recommended a sensitivity analysis in which local progression on RT is not regarded as an event for patients who subsequently achieve complete surgical resection. Secondary endpoints were recurrence-free survival, overall survival, acute toxicity profile of RT, perioperative and late complications, and QoL. The study was designed to provide 90% power to show an increase of 20% in the 5-year ARFS rate, from 50% to 70% (corresponding to a HR of 0.52) at 2-sided 5% significance level. Results: 266 patients from Europe, USA and Canada were randomized between January 2012 and April 2017; 198 patients (74.5 %) had liposarcoma (LPS). Eighteen patients were designated ineligible. Overall rate of re-operation for any complication was 10.1%: 13 (10.9%) and 12 (9.4%) patients in RT/S versus S groups. 19 pts (14%) progressed during RT, 4 of whom did not undergo surgery. 3-year ARFS was 60.4% (95% Confidence interval (CI) 51.4-68.2%) and 58.7% (49.5- 66.7%) (HR = 1.01, 95%CI 0.71-1.44, p=0.954) in RT/S versus S groups. In the sensitivity analysis, 3-year ARFS was 66.0% (57.1-73.5%) and 58.7% (49.5-66.7%) in RT/S versus S groups (HR = 0.84, 95% CI 0.58-1.21, p=0.340). In the LPS subgroup, 3-year ARFS (sensitivity analysis) was 71.6% (61.3-79.6%) and 60.4% (49.8-69.5%) in RT/S versus S groups (HR = 0.64, 95%CI 0.40-1.01, p =0.049). Conclusion: STRASS failed to demonstrate a benefit of pre-operative RT for RPS. In the exploratory analysis, preoperative RT may benefit the LPS subgroup. Funding Source: EORTC and EUROSARC FP7 278472. Clinical trial information: EORTC 62092.

Perioperative radiotherapy versus surgery alone for retroperitoneal sarcomas: a systematic review and meta-analysis

“…STRASS trial is the first, phase III, randomized, multicenter, EORTC study trying to assess whether there is a difference in abdominal recurrence-free survival between RPS patients treated with preoperative RT followed by surgery compared to surgery alone. 22 The results of STRASS trial were presented at the ASCO meeting in 2019 and failed to demonstrate a benefit of preoperative RT for RPS showing no difference in RFS between neoadjuvant RT and surgery vs. surgery alone arms with the exception of liposarcomas in an unplanned subset analysis. There was also, no difference in OS between the two groups.…”

Indikation zur prä-, post- und intraoperativen Strahlentherapie von Liposarkomen des Erwachsenenalters

“…Kürzlich wurden die vorläufigen Ergebnisse der randomisierten STRASS-Studie der EORTC in Abstractform publiziert [23], die den Stellenwert der neoadjuvanten RT gegenüber alleiniger Resektion in einem Kollektiv von 266 Patienten untersucht hat. Wie erwartet führte die neoadjuvante RT nicht zu wesentlichen Raten an höhergradigen Nebenwirkungen oder relevant erhöhten postoperativen Komplikationen, aber auch nicht zu einem Überlebensvorteil (3-Jahres-Gesamtüberleben 84 vs. 85 %) [23]. Überraschenderweise gelang es jedoch ebenfalls nicht, einen signifikanten Vorteil für die additive RT hinsichtlich des primären Endpunktes (3-Jahres-ARFS [ARFS: abdominelles rezidivfreies Überleben]), zu zeigen [23].…”

Surgical morbidity in retroperitoneal sarcoma resection

“…16 While the final trial results remain outstanding, the safety of preoperative external beam radiotherapy (EBRT) in the treatment of RPS has been confirmed on interim safety analysis, with no increased adverse events after resection of irradiated RPS. 17 Given the technical challenges of delivering large target volumes while minimizing toxicity to adjacent radiosensitive viscera, many Based on these available data, a consensus document from the TARPSWG stipulated that preoperative EBRT may be considered as a neoadjuvant strategy for well-selected patients within experienced centers. 23 IORT may be considered if a specific margin is considered at risk, although from a practical point of view the field often is too large for its application, and it is considered to be of no study-proven value.…”