What is the recommended treatment approach for a patient with sarcoma and lymph node (LN) spread, likely with elevated Lactate Dehydrogenase (LDH) levels?

Treatment of Sarcoma with Lymph Node Spread

For adult soft tissue sarcoma with regional lymph node metastases, aggressive multimodal treatment is warranted: wide surgical excision of both the primary tumor and involved lymph nodes, combined with adjuvant radiotherapy (50-60 Gy postoperatively or 50 Gy preoperatively) and chemotherapy for chemosensitive histologic subtypes, recognizing this represents likely systemic disease with poor prognosis. 1

Critical Context: Lymph Node Involvement is Rare and Ominous

• Regional lymph node metastases occur in only approximately 4% of adult soft tissue sarcomas and constitute a strong adverse prognostic factor 1
• These must be distinguished from soft tissue metastases that happen to involve lymph nodes—true regional nodal spread indicates lymphatic dissemination 1
• The presence of lymph node metastases signals likely systemic disease, not truly localized disease amenable to "adjuvant" therapy 1

Surgical Management

Wide excision of the primary tumor and involved lymph nodes is the cornerstone of treatment, though mutilating surgery should be avoided given the poor prognosis of these patients. 1

• Perform wide excision rather than radical mutilating procedures, as the systemic nature of disease makes aggressive local surgery of limited benefit 1
• Lymph node dissection should target clinically or radiologically evident nodal disease 1
• Plastic repairs and vascular grafting should be utilized as needed to achieve adequate resection 1

Radiation Therapy

Adjuvant radiotherapy is standard treatment for sarcoma with lymph node spread and should be administered to both the primary site and nodal basin. 1

• Postoperative radiotherapy: 50-60 Gy in 1.8-2 Gy fractions, with possible boosts up to 66 Gy depending on margin status 1, 2
• Preoperative radiotherapy: 50 Gy in standard fractionation, which may facilitate surgery 1, 2
• Radiation improves local control but does not improve overall survival 1, 2

Chemotherapy Approach

Chemotherapy should be administered for chemosensitive histologic subtypes, and may be given preoperatively (at least in part) or postoperatively. 1

• These treatment modalities should not be viewed as truly "adjuvant" since the context is that of likely systemic disease 1
• Doxorubicin-based regimens are most commonly used for chemosensitive histologies 1
• Chemotherapy is not used for histologies known to be insensitive to chemotherapy 1
• Regional hyperthermia combined with systemic chemotherapy showed local and disease-free survival advantage in one large randomized phase III trial for high-risk patients (G2-3, deep, >5 cm tumors) 1

Special Considerations for Extremity Tumors

• Isolated hyperthermic limb perfusion with TNF-α plus melphalan is an option for extremity-confined tumors, though this has no impact on systemic control and should be combined with other modalities 1
• This can be used alongside chemotherapy and radiation therapy 1

Prognostic Context and Elevated LDH

Elevated serum lactate dehydrogenase (LDH) at presentation is an adverse prognostic factor in sarcomas and is associated with metastatic disease, high histological grade, and worse disease-specific survival. 1, 3, 4, 5

• In Ewing's sarcoma, 83% of metastatic patients versus 41% of localized disease patients have elevated LDH at presentation 5
• High serum LDH levels (>253 IU/L) in soft tissue sarcoma predict presence of distant metastasis and worse disease-specific survival in high-grade tumors 3
• Elevated LDH should prompt more intensive staging workup and consideration of systemic therapy 3, 5

Critical Pitfalls to Avoid

• Do not perform extended lymph node dissection for clinically negative nodes (cN0) in soft tissue sarcoma—there is no survival benefit and only staging value 1
• Do not rely solely on PET-CT for nodal staging in pediatric and adolescent/young adult sarcomas—sensitivity is only 57% and specificity 52%, missing therapy-changing nodal disease 6
• Do not treat this as truly "adjuvant" therapy—the presence of lymph node metastases indicates systemic disease with poor prognosis requiring aggressive multimodal treatment 1
• Avoid mutilating surgery given the systemic nature and poor prognosis—functional preservation is important 1

Histology-Specific Considerations

• Certain sarcoma subtypes have higher propensity for lymphatic spread (epithelioid sarcoma, clear cell sarcoma, angiosarcoma, rhabdomyosarcoma, synovial sarcoma) and warrant more aggressive nodal evaluation 6
• Sentinel lymph node biopsy with SPECT-CT can identify nodal metastases in 25% of high-risk pediatric/AYA sarcoma patients, including cases missed by PET-CT 6