What factors differentiate early from late pulmonary metastases in soft-tissue sarcoma of the limbs?

Aims: It remains unclear what factors differentiate patients who present with early rather than late pulmonary metastases after resection of a soft-tissue sarcoma, and how their outcomes differ. The purpose of this study was to compare the survival of patients with early and late sarcoma metastases in the lungs, and to compare the differences between the two groups. Methods: We carried out a retrospective review of a prospectively maintained database, between January 1992 and November 2020, for all patients with a soft-tissue sarcoma of the pelvis and limbs who developed pulmonary metastases after definitive resection. We compared patients with early and late metastatic disease, defined as presentation before or after two years, respectively. Results: A total of 584 patients developed pulmonary metastases after surgical treatment of a soft-tissue sarcoma of the limb or pelvis. Overall, 79% had metastases within two years of surgery. The median time to pulmonary metastasis was nine months (IQR 4 to 20). The five-year disease-specific survival (DSS) from presentation was significantly worse for patients who developed early pulmonary metastases compared with those with late pulmonary metastases (12.2% (95% CI 9.2 to 16.0) vs 27.5% (95% CI 19.2 to 37.7), respectively; p < 0.001). Among patients undergoing surgical excision of pulmonary metastases, the five-year DSS from presentation was significantly worse for patients who developed early pulmonary metastases (27.2% (95% CI 19.8 to 36.1) vs 48.7% (95% CI 32.8 to 64.9); p = 0.014). Multivariable analysis revealed that older age (hazard ratio (HR) 1.02 (95% CI 1.01 to 1.03); p = 0.001), larger tumour size (HR 1.1 (95% CI 1.04 to 1.13); p < 0.001), and higher tumour grade (HR 2.0 (95% CI 1.26 to 3.1); p = 0.002) were associated with an increased risk of early pulmonary metastases, whereas previous local recurrence was associated with an increased risk of late pulmonary metastases (HR 3.3 (95% CI 1.8 to 5.4); p < 0.001). Conclusion: DSS is poor after the development of pulmonary metastases from a treated limb or pelvic soft-tissue sarcoma, but survival is worse for patients who present early.