Predicting Interval Pulmonary Metastasis in Extremity Soft Tissue Sarcoma Treated with Preoperative Radiotherapy: A...

Preoperative radiotherapy (RT) is widely used in high-risk extremity soft tissue sarcoma (STS) because of its benefits in local control and functional preservation. However, the interval between diagnosis and definitive surgery raises concern regarding the potential development of interval distant metastases, particularly in aggressive tumors. Data defining the incidence and predictors of such progression remain limited.

We conducted a retrospective cohort study of adult patients with nonmetastatic extremity STS treated with standardized preoperative RT followed by limb-sparing surgery between 2018 and 2024. All patients underwent baseline staging and mandatory preoperative chest computed tomography. The primary end point was new distant metastasis detected before surgery. Multivariable logistic regression was used to identify independent predictors, and a clinical risk score was developed.

Among 378 patients, interval distant metastases occurred in 29 (7.8%), almost exclusively involving the lungs. Tumor size greater than 12 cm, synovial sarcoma histology, FNCLCC grade 3, and age 50 years or younger were independently associated with interval metastatic progression. A 4-factor risk score stratified patients into low, intermediate, and high-risk groups, with metastasis rates of 2.4%, 8.4%, and 25.6%, respectively.

Interval metastasis during preoperative RT is rare and linked to unfavorable baseline tumor biology. This supports the treatment's feasibility for most patients and highlights the need for routine preoperative chest restaging. Interval metastasis in a standardized preoperative RT protocol for extremity STS occurs mainly in patients with adverse tumor characteristics. Routine preoperative chest CT restaging is necessary, and a simple 4-factor risk score may identify patients needing enhanced surveillance and personalized counseling.

Prognostic Level IV.