Systemic therapy outcomes following separation surgery versus maximal feasible resection for spinal metastases from non-small cell lung cancer: a real-world retrospective cohort study

Retrospective cohort study To compare systemic therapy outcomes between separation surgery and maximal feasible resection for patients with spinal metastases from non-small cell lung cancer (NSCLC). The presence of bone metastases has been associated with diminished response of primary tumors to systemic therapy, especially immunotherapy. However, in patients with spinal metastases, the impact of varying degrees of bone metastatic burden reduction on the efficacy of subsequent systemic therapy remains unknown. Adult patients (≥18 years) with spinal metastases from NSCLC who underwent surgical intervention at our institution between between January 2019 and June 2024 were retrospectively identified. Patients were categorized into two groups based on surgical strategy: separation surgery (SS) or maximal feasible resection (MFR). Systemic therapy response (objective response rate, disease control rate and best overall response) was assessed by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Surgical outcomes included blood loss, operating time, intraoperative blood transfusion, and complications. Overall survival (OS) was analyzed using the Kaplan–Meier method, and differences between groups were compared using the log-rank test. A total of 36 patients with spinal metastases from NSCLC were included. Patients in the MFR group exhibited a significantly higher disease control rate compared to those in the SS group (71.4% vs. 27.3%, P = 0.024). However, MFR was associated with increased surgical morbidity, including greater intraoperative blood loss [median 800 mL (IQR: 650–1425) vs. 500 mL (IQR: 100–1000), P = 0.041], a higher rate of intraoperative blood transfusion (71.4% vs. 31.8%, P = 0.048), and more intraoperative complications (28.6% vs. 0%, P = 0.017). There was no statistically significant difference in overall survival between the two surgical strategies [median 23.7 months (95% CI: 18.8–29.4) vs. 20.6 months (95% CI: 17.5–22.5); HR = 0.42 (95% CI: 0.16–1.08); P = 0.065]. However, Exploratory subgroup analyses indicated that MFR combined with denosumab was associated with a significantly lower hazard of death compared with SS plus bisphosphonates (HR = 0.14, 95% CI: 0.03–0.61, P = 0.009) and MFR plus bisphosphonates (HR = 0.15, 95% CI: 0.02–0.95, P = 0.044). A non-significant trend was also observed versus SS combined with denosumab (HR = 0.34, 95% CI: 0.10–1.18, P = 0.088). Compared to SS, MFR was associated with improved outcomes of subsequent systemic therapy in patients with spinal metastases from NSCLC, albeit at the cost of increased surgical trauma and a higher risk of intraoperative complications. In addition, MFR was associated primarily with disease stabilization rather than objective tumor regression. Notably, the combination of MFR with denosumab was associated with longer overall survival. These findings support the consideration of MFR in carefully selected patients, particularly when optimizing the response to systemic therapy is a key clinical objective. Importantly, given the small sample size, the observed differences in disease control rate and subgroup survival should be interpreted as hypothesis-generating. Level IV 1. MFR was associated with improved disease control compared to separation surgery in NSCLC spinal metastases. 2. MFR was associated with greater surgical trauma and higher complication rates. 3. No significant OS difference was found overall between surgical strategies. 4. MFR combined with denosumab was associated with significantly longer overall survival in subgroup analysis.