By Kenneth Cardona, MD

Retroperitoneal sarcomas (RPS), which represent approximately 15% of all soft tissue sarcomas, encompass a heterogeneous group of histologically distinct malignancies. Surgical resection remains the cornerstone of treatment and the current standard of care for patients with resectable disease. However, the role of systemic therapy in the management of high-risk RPS is ill-defined, with limited high-level evidence to support its routine use. Consequently, clinical practice varies considerably across institutions and geographic regions, reflecting ongoing uncertainty regarding the efficacy of systemic interventions in this context.

The STRASS 2 trial represents a significant advancement in the management of retroperitoneal sarcomas (RPS), particularly in high-risk subtypes such as dedifferentiated liposarcoma (DDLPS) and leiomyosarcoma (LMS). These tumors are known for their aggressive behavior and high likelihood of distant metastasis, which makes systemic treatment strategies increasingly relevant.

STRASS 2 is the first randomized phase 3 trial to evaluate the role of neoadjuvant chemotherapy—administered before surgery—in improving outcomes for these patients. Unlike previous studies that focused on radiotherapy (such as the original STRASS trial¹), STRASS 2 shifts attention to chemotherapy, reflecting an effort to address the systemic nature of disease progression in DDLPS and LMS.

STRASS 2 will enroll a total of 250 patients across these countries. Participants will be randomized to receive either three cycles of neoadjuvant chemotherapy followed by surgery or surgery alone. The cancer must be resectable. LMS must be either grade 2 or 3 (tumor size 5 cm or larger). DDLPS must be grade 3 (though grade 2 may be acceptable under certain conditions, as noted in the Physician Fact Sheet).

One of the novel aspects of STRASS 2 is its histology-tailored chemotherapy regimens, with doxorubicin plus ifosfamide used for DDLPS, and doxorubicin plus dacarbazine for LMS. This approach recognizes the biological diversity of soft tissue sarcomas and represents a move toward more personalized, subtype-specific treatments.

If successful, STRASS 2 has the potential to reshape the standard of care for high-risk retroperitoneal sarcoma, moving from a solely surgical approach to one that incorporates systemic chemotherapy in a histology-specific, preoperative setting. This could lead to improved disease-free and overall survival in a patient population where therapeutic advances have historically been limited.

STRASS and STRASS 2 are the first large, international, randomized studies ever performed in retroperitoneal soft tissue sarcoma. STRASS 2 is the first study to activate from the ECOG-ACRIN Cancer Research Group’s Sarcoma Working Group, formed in 2020. The trial is open in Europe, Canada, Australia, New Zealand, Japan, and the United States through ECOG-ACRIN.

Learn more about EA7211/STRASS 2 at ecog-acrin.org.

Dr. Cardona (Emory University/Winship Cancer Institute) is the study chair for this international trial led in the United States by the ECOG-ACRIN Cancer Research Group, with sponsorship from the National Cancer Institute. Richard Riedel, MD (Duke University/Duke Cancer Institute) is the study co-chair in the US.

Alessandro Gronchi, MD is the study chair in Europe, where the trial sponsor is the European Organisation for Research and Treatment of Cancer (EORTC). Winan Van Houdt, MD, PhD is the study co-chair in Europe.

^{1Bonvalot S, Gronchi A, Le Péchoux C, et al. Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): a multicentre, open-label, randomised, phase 3 trial. The Lancet Oncology, Volume 21, Issue 10, 2020Oct21 (10): 1366 – 1377. DOI: 10.1016/S1470-2045(20)30446-0.}