Pulmonary metastasectomy and response-adapted preoperative surveillance in resectable metastatic osteosarcoma: a single-center retrospective cohort study with long-term follow-up.

BACKGROUND: Pulmonary metastasectomy remains the standard of care for resectable metastatic osteosarcoma. However, controversy persists regarding minimally invasive surgery versus thoracotomy for occult nodule detection, the optimal use and duration of preoperative systemic therapy and prognostic factors associated with long-term survival. This study aimed to evaluate surgical approaches, assess the use and duration of preoperative systemic therapy, and identify prognostic factors associated with long-term survival in this population. METHODS: At a single center, we retrospectively reviewed 159 patients who underwent 229 pulmonary metastasectomies from 2000 to 2022. Eligible patients had pathologically confirmed osteosarcoma, resectable pulmonary metastatic disease, surgery intended to remove all known lesions and postoperative follow-up. The primary endpoint was post-metastasis survival (PMS), defined from metastatic diagnosis to death or the last follow-up. Computed tomography (CT) was scheduled every 4-8 weeks during preoperative surveillance and at prespecified postoperative intervals. Surgical approaches included conventional thoracotomy, mini-thoracotomy, and video-assisted thoracoscopic surgery (VATS). Preoperative strategies comprised upfront surgery or preoperative systemic therapy with first- or second-line chemotherapy, tyrosine kinase inhibitors (TKIs), or their combination. Oncological and perioperative outcomes were analyzed with a median follow-up of 79.1 months. RESULTS: The median age was 17.0 years, 106 (66.7%) patients were male, and 185 of 229 procedures (80.8%) followed preoperative systemic therapy. The 3- and 5-year PMS were 52.2% and 36.0%, respectively. Despite advances in CT resolution, palpation-assisted mini-thoracotomy identified more occult lesions than VATS (43.4% vs. 6.8%, P=0.004), with comparable rates of surgical complications. However, no significant difference in survival was observed between mini-thoracotomy and VATS. Remarkably, response to preoperative systemic therapy was the strongest independent predictor of survival, with a 5-year survival rate of 41.1% in responders versus 0.0% in non-responders (hazard ratio =0.22, P<0.001). Responders also exhibited a trend toward higher immune diversity (P=0.055) and increased CD8+ T cell infiltration (P=0.098) in metastasectomy specimens. Using tumor response modeling, we identified a 2-3-month period as the optimal duration for preoperative surveillance. CONCLUSIONS: In this single-center retrospective cohort, preoperative surveillance and response-adapted strategy, combined with palpation-assisted mini-thoracotomy, was associated with favorable long-term outcomes of metastasectomy in patients with resectable metastatic osteosarcoma. However, given the observational design and modest sample size, these findings are exploratory and require validation in larger multicenter prospective studies.