STRASS 2 target trial emulation: Bridging the gap between trial efficacy and real-world effectiveness

Area of Science:

• Oncology
• Surgical Oncology
• Medical Oncology

Background:

• The Surgery With or Without Neoadjuvant Chemotherapy in High Risk RetroPeritoneal Sarcoma (STRASS 2) trial investigates neoadjuvant chemotherapy's impact on high-risk retroperitoneal sarcoma.
• Real-world effectiveness of neoadjuvant chemotherapy for retroperitoneal sarcoma is evaluated using target trial emulation.

Purpose of the Study:

• To emulate the STRASS 2 trial using real-world data.
• To assess the impact of neoadjuvant chemotherapy followed by surgery versus upfront surgery on overall survival in retroperitoneal sarcoma patients.

Main Methods:

• Target trial emulation using the National Cancer Database (2010-2022).
• Inclusion of patients with dedifferentiated liposarcoma and leiomyosarcoma meeting STRASS 2 eligibility criteria.
• Comparison of neoadjuvant chemotherapy plus surgery versus upfront surgery using multivariable-adjusted and inverse probability of treatment-weighted Cox regression models.

Main Results:

• Among 2,215 eligible patients, 9.4% received neoadjuvant chemotherapy followed by surgery, and 90.6% underwent upfront surgery.
• Neoadjuvant chemotherapy did not improve overall survival compared to upfront surgery across all analytical models (HR 0.73-0.75).
• Neoadjuvant chemotherapy was not associated with improved R0/R1 resection rates (OR 1.96).

Conclusions:

• Neoadjuvant chemotherapy does not offer an overall survival benefit for patients with resectable retroperitoneal sarcoma.
• Target trial emulation is a valuable method for generating real-world evidence in rare and heterogeneous cancers, complementing randomized trials.