The goal of this clinical trial is to explore the potential survival benefits of neoadjuvant chemotherapy combined with target treatments followed by radical surgery in patients with primary high-risk/grade retroperitoneal sarcoma.

The main questions it aims to answer are:

• Whether the 1,3-year progression-free survival time(PFS) is prolonged in the neoadjuvant therapy group, compared with the surgery-only group.
• The Overall survival time in the two groups.
• The safety and tolerance in the neoadjuvant therapy group.

Participants will be allocated into two groups once they meet the inclusion criteria.

• Surgery-only Group: Patients will directly undergo surgeries after the confirmation of diagnosis through pre-operative biopsy.
• Neoadjuvant therapy group: Patients will receive the neoadjuvant chemotherapy combined with target treatment for three circles before the following sarcoma resectional surgeries.

Inclusion Criteria:

• Histologically proven primary high-risk Retroperitoneal sarcoma(RPS) (Including Dedifferentiated liposarcoma (DDLPS), leiomyosarcoma(LMS), Undifferentiated pleomorphic sarcoma(UPS), Solitary fibrous tumor(SFT)).

• Primary localized RPS without histories of surgical resection, chemo- or radio-therapy, targeted therapy. Patients who underwent laparotomy with biopsy only will also be considered as primary cases.

• Without histories of second malignant tumors.

• In DDLPS

  • Diagnosis should be confirmed based on MDM2(Mouse double minute 2 homolog) and CDK4(Cyclin-dependent kinase 4) expression on IHC (immunohistochemistry), while MDM2 amplification in the Fish test is highly recommended.
  • All grade 2-3 DDLPS can be included.

• In LMS

  • All grades of LMS can be included.
  • Tumor size ≥10cm

• In UPS or SFT

  • All grades of UPS can be included.
  • High-risk SFT with a score ≥6 in 'Risk stratification of SFT for development of metastasis' introduced in The 5th edition of the WHO(World Health Organization) Soft tissue sarcoma classification.

• Sarcoma without protruding across the diaphragm

• Possibility of R0/R1 resection evaluated through preoperative MDT(multi-disciplinary team) discussion

• No multi-organ or system dysfunction/failure or patients with slight dysfunction of organ/system could be easily recovered

• Tolerable of chemotherapy and surgery through MDT evaluation and tests.

• American Society of Anesthesiologist (ASA) ≤3

• Fully understand the informs and consent to participate in the study.

Exclusion Criteria:

• Sarcoma confirmed originating from the GI tract, uterus, or urinal tract.
• Patients included in the study through preoperative biopsy or MDT discussion, with WDLPS, grade 1 LPS, or other types of tumors not mentioned in the Inclusion criteria evaluating through final pathological findings.
• Sarcoma protruded into the chest cavity evaluated through preoperative imaging or surgical reports.
• Metastasis confirmed pathologically or highly suspicious metastatic lesions through radiological findings, PET-CT(Positron emission tomography) is highly recommended, MDT discussion and evaluation are needed.
• Histories of administration of Anthracyclines, Ifosfamide, and targeted agents.
• Severe contradiction to surgery and chemotherapies, including persistent myelosuppression, myocardial/cerebral/pulmonary infarction, uncontrolled cardiac arrhythmia, etc within the last 6 months
• Indication of severe infection or undergoing surgeries with high-risk hemorrhages in one month.
• Persistent one or more organ or system dysfunctions, could not be recovered prior to the study.
• Female patients who are pregnant or breastfeeding or female and male patients of reproductive potential who are not willing to employ effective birth control methods.
• Patients with psychological conditions