Recurrent retroperitoneal sarcoma: beyond resectability toward a biology-based therapeutic framework

Recurrent retroperitoneal sarcoma remains a significant therapeutic challenge. Recurrence does not always indicate treatment failure but reflects different tumor biologies with diverse implications for local and systemic management. This review proposes a biology-based framework for recurrent RPS that incorporates histology, disease-free interval, tumor growth kinetics, multifocality, resectability, functional reserve, and therapeutic proportionality. Histological subtype significantly influences recurrence patterns. Well-differentiated liposarcoma often follows a chronic local-regional course, where multiple surgeries can offer long-term control. In contrast, leiomyosarcoma more commonly shows early systemic spread, which diminishes the benefit of repeated local treatments. Disease-free interval and tumor growth rate are important dynamic indicators that improve prognosis and assist in timing treatment. Complete resection is essential for a meaningful survival benefit, but resectability alone does not justify surgery. Radiotherapy and systemic therapy serve complementary roles, mainly in local control, biological modulation, and palliation. Prognostic tools and nomograms aid in initial risk assessment, but are most valuable when combined with dynamic factors that reflect tumor behavior. Future advancements will rely on clinically relevant biomarkers, adaptive predictive models, personalized surveillance, recurrence-focused clinical trials, and shared decision-making based on meaningful patient benefits.