Abstract
Opinion statement
Well-differentiated liposarcoma (WDLPS) is a low-grade malignancy characterized by an indolent clinical course and a strong tendency for local recurrence. Unlike other sarcoma subtypes, pure WDLPS has a very low metastatic potential. However, in the course of the disease, dedifferentiation may occur and is associated with a substantially higher risk of metastases and mortality. Surgery remains the cornerstone of treatment for both primary and recurrent abdominal WDLPS, when a complete resection is possible. The role of systemic therapy in WDLPS is less clearly defined. Conventional cytotoxic chemotherapy generally has limited activity in pure WDLPS, and most clinical trials have included both WDLPS with dedifferentiated liposarcoma (DDLPS) or other liposarcoma subtypes, making the data for pure WDLPS difficult to interpret. Therefore, in clinical practice, we consider systemic treatment for patients with unresectable, symptomatic disease and in cases of repeated recurrences in which further local treatment is not possible. For selected patients with indolent and asymptomatic disease, active surveillance remains an appropriate strategy. The recent development of treatments directed against molecular alterations in WDLPS, namely CDK4 and MDM2 amplifications, have opened up a new era in the systemic treatment of this disease. Among these, anti-CDK4 agent palbociclib has shown the most mature clinical evidence to date, including recent results of overall survival data. MDM2 inhibition and combinations targeting both CDK4 and MDM2 represent promising areas which are currently under investigation. Due to the rarity of WDLPS and the lack of evidence from prospective studies, enrollment in clinical trials should be prioritized whenever possible.