What Are the Oncologic Outcomes of Patients With Osteosarcoma and Venous Tumor Thrombi Managed by an Aggressive Multidisciplinary Approach of Chemotherapy and Surgical Resection?

BACKGROUND: Macroscopic venous tumor thrombus (VTT) is a rare but aggressive manifestation of osteosarcoma that poses substantial challenges for both surgical management and systemic disease control. Our previous work characterized its frequency, radiographic features, and adverse prognostic association, particularly in pelvic osteosarcoma; however, surgical management was heterogeneous. The patient-level outcomes achieved after a standardized multidisciplinary treatment approach and the association between VTT resection strategy and postoperative oncologic outcomes remain unclear. QUESTIONS/PURPOSES: (1) What were the oncologic outcomes of patients with osteosarcoma with macroscopic VTT treated under a standardized treatment algorithm incorporating aggressive surgical resection? (2) Did the choice of VTT resection strategy affect oncologic outcomes? METHODS: We screened the records of 39 patients with treatment-naive osteosarcoma and macroscopic VTT identified on imaging who were treated according to a standardized multimodal treatment algorithm between 2019 and 2024. This algorithm consisted of standardized multimodal imaging at diagnosis to detect and characterize VTT. After biopsy confirmation, patients received four-agent neoadjuvant chemotherapy, preoperative inferior vena cava filter placement when technically feasible, and repeat imaging to reassess the resectability of both the primary tumor and VTT. Surgery was undertaken only when both lesions were considered resectable. VTT involving peripheral venous branches or completely occluded and enlarged major veins was managed with en bloc venous resection, whereas thrombectomy was performed for VTT involving patent or partially patent major veins. Postoperative chemotherapy was initiated 2 to 3 weeks after surgery. After excluding one patient without pathologic confirmation of the macroscopic VTT, two patients in whom en bloc resection of the primary tumor was not achieved, and seven patients who did not receive postoperative chemotherapy, 29 patients were included in this retrospective analysis. The study population was young (mean ± SD age 16 ± 7 years), with a slight male predominance (17 of 29 patients), and primary tumors were distributed between the extremities (16 of 29) and pelvis (13 of 29). More than half of the patients presented with metastatic disease (16 of 29), most VTTs involved major venous trunks (22 of 29), and 20 of 29 patients had < 90% tumor necrosis after neoadjuvant chemotherapy. Given the high risk of early progression in these patients, progression-free survival (PFS) was selected as the primary endpoint. Secondary endpoints included overall survival (OS), local recurrence-free survival (LRFS), and metastasis PFS (MPFS). RESULTS: Patients treated under the standardized algorithm had limited durable disease control, with disease progression in 26 of 29 patients, a median PFS of 7 months (95% confidence interval [CI] 0 to 16), and an estimated 2-year OS of 60%. Patients with localized disease had longer PFS (median 13 months [95% CI 8 to 19] versus 5 months [95% CI 4 to 5]; p = 0.046) and MPFS (median 13 months [95% CI 8 to 19] versus 4.6 months [95% CI 4 to 5]; p = 0.04) than those with metastatic disease. There were no differences in OS (not reached versus median 32 months [95% CI 10 to 54]; p = 0.52), PFS (median 11 months [95% CI 0 to 31] versus 6 months [95% CI 3 to 9]; p = 0.62), LRFS (median 21 months [95% CI 9 to 34] versus 61 months [95% CI 2 to 120]; p = 0.54), and MPFS (median 13 months [95% CI 0.3 to 25] versus 8 months [95% CI 3 to 13]; p = 0.24) between patients who had thrombectomy versus en bloc venous resection. CONCLUSION: Despite a standardized multidisciplinary approach incorporating perioperative chemotherapy and aggressive resection of both the primary tumor and macroscopic VTT, progression remained frequent, and durable disease control was uncommon. Among these 29 selected patients, VTT resection strategy-thrombectomy versus en bloc venous resection-was not detectably associated with oncologic outcomes, although the two groups were not directly comparable. Surgeons should recognize that osteosarcoma with macroscopic VTT is a rare, highly aggressive condition for which current treatment modalities seldom achieve a cure and should carefully balance the potential oncologic benefit of aggressive surgery against its morbidity. Future prospective multicenter studies should refine patient-level selection criteria and directly evaluate the incorporation of adjuvant radiotherapy into this standardized treatment algorithm. Novel systemic therapies should also be investigated to improve control of metastatic and rapidly progressive disease. LEVEL OF EVIDENCE: Level III, therapeutic study.