What is the treatment approach for liposarcoma?

Treatment Approach for Liposarcoma

Complete surgical resection with negative margins performed by a surgeon with specific sarcoma expertise is the cornerstone of liposarcoma treatment, with the surgical approach and adjuvant therapy tailored to histologic subtype and anatomic location. 1

Initial Management Principles

All patients with suspected liposarcoma must be referred to high-volume sarcoma centers and discussed at a multidisciplinary sarcoma tumor board before treatment initiation. 1 The best chance of cure occurs at primary presentation, making expert initial management critical. 1

Pre-Treatment Evaluation

Core needle biopsy (14-16 gauge) is mandatory for pathological diagnosis to guide treatment decisions, unless otherwise determined by the sarcoma tumor board. 1 The risk of needle track seeding is minimal and should not prevent biopsy. 1

For retroperitoneal lesions, the biopsy pathway must be carefully planned to avoid transperitoneal approaches, with retroperitoneal access preferred when technically feasible. 1 Open or laparoscopic biopsies must be avoided. 1

Staging requires contrast-enhanced CT of chest, abdomen, and pelvis. 1 MRI is an option for pelvic tumors or when specific tumor extent assessment is needed. 1 For retroperitoneal disease, functional assessment of the contralateral kidney is necessary. 1

Surgical Treatment by Location and Subtype

Extremity and Superficial Trunk Liposarcoma

Wide excision achieving R0 (negative) margins is the standard surgical procedure. 1, 2 This involves removing the tumor with a rim of normal tissue, though margins can be minimal when adjacent to resistant anatomical barriers (muscular fasciae, periosteum, perineurium). 1

For atypical lipomatous tumors (ALT)/well-differentiated liposarcoma of extremities:

• Complete en bloc marginal resection, even if classified as R1 microscopically, provides excellent long-term local control 1, 2
• Preservation of adjacent neurovascular structures is appropriate, as dedifferentiation is extremely rare in extremity ALT 1
• In older patients with significant comorbidities, radiological surveillance can be considered as an alternative to surgery 1

Retroperitoneal Liposarcoma

Surgical strategy must be histology-specific: 1

For well-differentiated and dedifferentiated liposarcoma:

• Extended surgical resection removing the tumor en bloc with adherent structures and all ipsilateral fat is recommended to minimize microscopic positive margins 1
• This typically necessitates ipsilateral nephrectomy, hemicolectomy, psoas fascia/muscle resection, and distal pancreatectomy/splenectomy on the left side 1
• Liposarcomas have poorly defined margins with inherent high local recurrence risk, justifying extended resection 1

For retroperitoneal leiomyosarcoma:

• Complete resection of tumor with involved organs while preserving adjacent uninvolved organs 1
• Extended resections do not improve outcomes, as prognosis is dictated by metastatic disease rather than local recurrence 1

Grossly incomplete resection is potentially harmful and should be avoided through careful imaging review and referral to appropriate centers. 1

Radiation Therapy

Extremity and Trunk Disease

Postoperative radiation therapy (50-60 Gy) is standard for high-grade, deep lesions >5 cm. 1 Radiation improves local control but not overall survival. 1

For high-grade, deep lesions <5 cm, radiation therapy should be administered with few exceptions. 1 For low-grade lesions, radiation is added selectively based on size, depth, and anatomical site considerations. 1

Preoperative radiation (50 Gy) is an alternative option that may be preferred in selected cases. 1

Retroperitoneal Disease

Preoperative radiation therapy for retroperitoneal liposarcoma did not improve recurrence-free survival or overall survival in a randomized trial 1, though subgroup analysis suggested potential benefit in low-intermediate grade liposarcoma. 1

For resectable low-intermediate grade retroperitoneal liposarcoma, preoperative radiation can be discussed. 1 However, for high-grade dedifferentiated liposarcoma and leiomyosarcoma, preoperative radiation should not be used. 1

Postoperative radiation has limited value and significant toxicity; it should only be considered in highly selected cases with well-defined areas at risk. 1

Neoadjuvant and Adjuvant Chemotherapy

Neoadjuvant chemotherapy can be considered for:

• Technically unresectable/borderline resectable disease that could be rendered resectable by downsizing 1
• Chemosensitive histologies (myxoid/round cell liposarcoma is chemosensitive; well-differentiated liposarcoma is not) 1, 3
• High-grade dedifferentiated liposarcoma (currently under investigation in prospective trials) 1

Regional hyperthermia combined with systemic chemotherapy showed local progression-free survival and disease-free survival advantages in one Phase III trial. 1

The value of adjuvant chemotherapy is not established and should be discussed individually for cases at high risk for metastatic disease. 1

Systemic Therapy for Advanced/Metastatic Disease

First-Line Treatment

Doxorubicin-based chemotherapy (with or without ifosfamide) is standard first-line treatment for unresectable or metastatic disease when patient performance status is good. 1, 3, 4, 5

Chemosensitivity varies by subtype:

• Myxoid/round cell and pleomorphic liposarcoma are chemosensitive 3, 4, 6
• Well-differentiated and dedifferentiated liposarcoma are generally chemoresistant 1, 3

Second-Line and Beyond

Trabectedin is an established option in second and further lines with Level I evidence. 1, 4, 5

Eribulin showed greater than 7-month improvement in median overall survival in liposarcoma subgroup analysis of a Phase III trial. 5

Pazopanib is an option for non-adipogenic sarcomas in second and further lines. 1

Emerging Targeted Therapies

For well-differentiated/dedifferentiated liposarcoma:

• Palbociclib (CDK4/6 inhibitor) is being investigated 1, 3
• MDM2 antagonists are under evaluation 3

NTRK inhibitors are standard treatment for NTRK-rearranged sarcomas and can be considered preoperatively when cytoreduction would improve morbidity and function. 1

Oligometastatic Disease

For patients with oligometastatic disease, surgery, radiotherapy, or ablative therapies (radiofrequency ablation, stereotactic body radiation therapy, cryotherapy, microwave, electrochemotherapy) should be considered on an individual basis, though survival benefit data are limited. 1

Surgical resection of lung metastases is appropriate for selected patients, particularly those with myxoid liposarcoma (which has atypical metastatic patterns with preponderance of extrapulmonary sites). 6

Follow-Up Strategy

Intermediate/high-grade patients: Every 3-4 months for the first 2-3 years, then twice yearly until year 5, then annually. 1

Low-grade patients: Every 4-6 months for local relapse assessment, with chest imaging at longer intervals for the first 3-5 years, then annually. 1

Low-grade retroperitoneal liposarcomas may recur late (even after 10 years), while high-grade disease mostly recurs within 5 years. 1 Cross-sectional imaging detects asymptomatic recurrences earlier, though benefit of earlier detection remains controversial. 1

Critical Pitfalls to Avoid

• Never perform grossly incomplete resection of retroperitoneal sarcomas outside carefully selected palliative scenarios 1
• Do not use transperitoneal biopsy approaches for retroperitoneal lesions 1
• Avoid open or laparoscopic biopsies 1
• Do not apply uniform treatment strategies across liposarcoma subtypes—histology dictates prognosis and treatment sensitivity 6
• Re-excision at a reference center must be considered for R1 resections if adequate margins can be achieved without major morbidity 1