Neoadjuvant vs. Adjuvant Chemotherapy in Localized UPS Sarcoma

Introduction to Chemotherapy Recommendations

The National Comprehensive Cancer Network recommends that perioperative chemotherapy (neoadjuvant or adjuvant) should only be considered for high-risk patients, particularly those with high-grade (grade 3), large-sized (≥5 cm) tumors, and deep location 1, 2
Neoadjuvant chemotherapy can be considered for tumors with borderline resectability or to downsize the tumor before surgery, according to the National Comprehensive Cancer Network 2

Neoadjuvant chemotherapy can improve the resectability of tumors with unfavorable anatomical locations, as suggested by the National Comprehensive Cancer Network 2
It allows for the assessment of tumor response to chemotherapy (histological response), which can provide prognostic information and influence further treatment strategy, as stated by the National Comprehensive Cancer Network 3, 4
A good histological response (>90% necrosis) can be associated with improved survival rates, according to the National Comprehensive Cancer Network 3
Neoadjuvant chemotherapy may delay definitive surgical treatment, as noted by the Cancer Treatment Reviews 2

Adjuvant chemotherapy does not delay definitive surgical treatment, as stated by the National Comprehensive Cancer Network 2
It does not allow for the assessment of tumor response to chemotherapy before surgery, as noted by the National Comprehensive Cancer Network 3

The decision for neoadjuvant or adjuvant chemotherapy should be made in a multidisciplinary tumor board at a specialized sarcoma center, as recommended by the Cancer Treatment Reviews 5, 6
The assessment of histological response after neoadjuvant chemotherapy can provide prognostic information and influence further treatment strategy, according to the National Comprehensive Cancer Network 3, 4
The toxicity of chemotherapy must be weighed against the potential benefit, especially in older patients or those with comorbidities, as noted by the National Comprehensive Cancer Network 2

The evidence for the effectiveness of chemotherapy in retroperitoneal sarcomas is limited and does not show a clear survival benefit, as stated by the Cancer Treatment Reviews 5, 6, 7
Current guidelines recommend participation in clinical trials for patients with localized UPS who are candidates for perioperative chemotherapy, as suggested by the Cancer Treatment Reviews 5, 6

The European Society for Medical Oncology (ESMO) recommends neoadjuvant chemotherapy with at least 3 cycles of an anthracycline-ifosfamide combination (AI) for high-risk patients with a predicted 10-year overall survival of <60% 8, 9
Neoadjuvant chemotherapy allows for the assessment of tumor response before surgery, which can provide prognostic information and influence further treatment strategy 8
The ESMO-EURACAN-GENTURIS guidelines recommend neoadjuvant chemotherapy for high-risk patients with UPS 9, 8

The National Comprehensive Cancer Network (NCCN) recommends 3-4 cycles of anthracycline-based chemotherapy in the adjuvant setting 10, 11
Adjuvant chemotherapy can improve overall survival in patients with localized UPS, particularly for tumors ≥5 cm 10, 11

The decision for neoadjuvant or adjuvant chemotherapy should be made in a multidisciplinary tumor board at a specialized sarcoma center, considering the potential benefits and toxicity of chemotherapy 12, 13
For patients with retroperitoneal sarcoma, the evidence for the effectiveness of chemotherapy is limited and shows no clear survival benefit 12, 13

For high-risk patients with UPS, neoadjuvant chemotherapy with 3 cycles of an anthracycline-ifosfamide combination is recommended 9, 8
In the adjuvant setting, 3-4 cycles of anthracycline-based chemotherapy are recommended 10, 11

The National Comprehensive Cancer Network (NCCN) recommends that patients with good histological response (tumor necrosis >90%) should receive additional cycles of the same chemotherapy 14, 15
For patients with poor response (tumor necrosis <90%), a switch to a different chemotherapy regimen may be considered, although attempts to improve outcomes by modifying adjuvant chemotherapy have been unsuccessful so far 14, 15