STRASS (EORTC-62092)

Background

STRASS (EORTC-62092) — Phase III open-label, randomised trial. N=266 patients with localised, primary, operable retroperitoneal sarcoma (RPS) not previously treated, WHO PS ≤2. Enrolled at 31 centres in 13 countries in Europe and North America (2012–2017). Hypothesis: preoperative radiotherapy before surgery for RPS would reduce abdominal recurrence by sterilising the surgical margin and treating adjacent organs. Registration NCT01344018.

Interventions and follow up

Arm A: Preoperative radiotherapy 50.4 Gy in 28 fractions → surgery
Arm B: Surgery alone
Primary endpoint: Abdominal recurrence-free survival (ARFS), assessed by investigator; intention-to-treat
mFollow up: 43.1 months (IQR 28.8–59.2)

Results

Abdominal RFS: Median 4.5 years (RT+surgery) vs 5.0 years (surgery alone); HR 1.01 (95% CI 0.71–1.44), P=.95 — not significant
RT delivery: 89% of RT group received RT; 96% of surgery group had surgery

Adverse events

Main adverse events: Grade 3–4 lymphopenia: 77% (RT+surgery) vs 1% (surgery alone). Grade 3–4 anaemia: 12% vs 8%. Grade 3–4 hypoalbuminaemia: 12% vs 4%. Serious AEs: 24% (RT+surgery) vs 10% (surgery alone). One treatment-related death in RT arm (gastropleural fistula). No treatment-related deaths in surgery-alone arm.

Conclusions

Preoperative radiotherapy before surgery for retroperitoneal sarcoma did not improve abdominal recurrence-free survival compared with surgery alone and was associated with significantly more adverse events including one treatment-related death. Preoperative RT should not be considered standard of care for resectable primary RPS.

Key Limitations

ARFS is a novel composite endpoint that may not fully capture local recurrence patterns. A prespecified exploratory analysis suggested possible benefit in well-differentiated liposarcoma (WD-LPS), which cannot be confirmed without further study. Inclusion of multiple histotypes (LPS, LMS, SFT, MPNST) with heterogeneous relapse patterns may have diluted any signal. The RT dose (50.4 Gy) and technique varied; newer ablative approaches or proton RT were not evaluated. The STRASS-2 trial is examining preoperative RT in dedifferentiated LPS specifically.

Clinical Context

STRASS definitively answers that preoperative RT is not beneficial for unselected RPS. Surgery at a high-volume sarcoma referral centre remains the cornerstone of RPS management. The STRASS-2 trial (NCT04307563) is investigating preoperative RT specifically in dedifferentiated LPS, a biologically distinct RPS subtype with higher local recurrence rates. ESMO guidelines recommend against preoperative RT for RPS outside of clinical trials. The surgical principle of compartmental resection (en-bloc resection of involved organs) continues to be emphasised for local control.
Arm A (preoperative RT + surgery, n=133): IMRT or 3D-conformal RT 50.4 Gy in 28 daily fractions of 1.8 Gy, then surgical resection
Arm B (surgery alone, n=133): Macroscopically complete surgical resection of tumour with en-bloc organ resection as needed

References