Landmark Series: A Review of Landmark Studies in the Treatment of Primary Localized Retroperitoneal Sarcoma

Abstract

Primary localized retroperitoneal soft tissue sarcomas (RPS) have shorter survival than other soft tissue sarcoma sites owing to higher local recurrence rates associated with histologic types most commonly found in this location, large tumor size at diagnosis (median 20 cm), and anatomical constraints of surgery in the retroperitoneum. The only curative treatment for RPS has traditionally been complete macroscopic en bloc resection with adjacent structures that cannot be surgically separated from the tumor. Compartmental resection, incorporating adjacent organs and soft tissues en bloc, even without overt infiltration at the time of surgery, performed in sarcoma referral centers may reduce local recurrence rates. Preoperative radiotherapy has not been shown to reduce early 3-year local recurrences in a phase III, international, randomized, controlled trial (STRASS). Longer follow-up is needed to determine whether well-differentiated and low-grade dedifferentiated liposarcoma prone to late local recurrences may benefit. Currently, there is no level 1 evidence to support the use of perioperative systemic therapy. Observational studies suggest that patients with high-grade histologies and borderline resectable RPS may benefit. A phase III, international, randomized, controlled trial (STRASS2) is currently evaluating a histology-tailored chemotherapy regimen for patients with leiomyosarcoma and dedifferentiated liposarcoma at high risk of distant metastatic recurrence. Novel biomarkers can help determine prognosis and more accurately predict response to treatment, but more research is needed to translate these discoveries into therapeutic benefits. Refined molecular data for histological types will allow personalized surgery, radiotherapy, and systemic therapy with lower toxicity and improved survival in the future.