Abstract

Simple SummaryAlthough oligometastatic disease is common, present in up to 25% of patients with stage IV non-small cell lung cancer, management of it remains challenging. Numerous other studies have shown promising results in patients who undergo local treatment of both the primary tumor and the metastases. In this, the largest single-institution analysis of patients undergoing primary tumor surgical resection for oligometastatic disease, we have demonstrated encouraging long-term event-free survival, overall survival, and postrecurrence survival, with the greatest benefit in patients who undergo neoadjuvant therapy and those with limited intrathoracic disease. Therefore, in carefully selected patients, surgical resection of the primary tumor can be an important component of multimodal management for advanced-stage non-small cell lung cancer.Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of newly diagnosed cases of NSCLC. The oligometastatic state—≤5 extrathoracic metastatic lesions in ≤3 organs—is present in ~25% of patients with stage IV disease and is associated with markedly improved outcomes. We retrospectively identified patients with extrathoracic oligometastatic NSCLC who underwent primary tumor resection at our institution from 2000 to 2018. Event-free survival (EFS) and overall survival (OS) were estimated using the Kaplan–Meier method. Factors associated with EFS and OS were determined using Cox regression. In total, 111 patients with oligometastatic NSCLC underwent primary tumor resection; 87 (78%) had a single metastatic lesion. Local consolidative therapy for metastases was performed in 93 patients (84%). Seventy-seven patients experienced recurrence or progression. The five-year EFS was 19% (95% confidence interval (CI), 12–29%), and the five-year OS was 36% (95% CI, 27–50%). Factors independently associated with EFS were primary tumor size (hazard ratio (HR), 1.15 (95% CI, 1.03–1.29); p = 0.014) and lymphovascular invasion (HR, 1.73 (95% CI, 1.06–2.84); p = 0.029). Factors independently associated with OS were neoadjuvant therapy (HR, 0.43 (95% CI, 0.24–0.77); p = 0.004), primary tumor size (HR, 1.18 (95% CI, 1.02–1.35); p = 0.023), pathologic nodal disease (HR, 1.83 (95% CI, 1.05–3.20); p = 0.033), and visceral-pleural invasion (HR, 1.93 (95% CI, 1.10–3.40); p = 0.022). Primary tumor resection represents an important treatment option in the multimodal management of extrathoracic oligometastatic NSCLC. Encouraging long-term survival can be achieved in carefully selected patients, including those who received neoadjuvant therapy and those with limited intrathoracic disease.

Highlights

  • Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of all newly diagnosed cases of NSCLC [1,2]

  • Aggressive therapy aimed at eliminating all metastatic sites has been shown to lead to durable disease control in other cancers [7], this treatment paradigm remains controversial in metastatic NSCLC, for which definitive systemic therapy with or without radiotherapy continues to be the cornerstone of management

  • We investigated event-free survival (EFS) and overall survival (OS), and determined factors associated with these outcomes, in our institutional cohort of patients who underwent primary tumor resection in the management of oligometastatic NSCLC

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Summary

Introduction

Stage IV non-small cell lung cancer (NSCLC) accounts for 35 to 40% of all newly diagnosed cases of NSCLC [1,2]. The oligometastatic state—defined as ≤5 extrathoracic metastatic lesions in ≤3 organs [4]— is present in approximately 25% of patients with stage IV disease [5] and, compared with more-extensive disease, is associated with markedly improved outcomes, with a five-year survival up to 30% [6]. A landmark phase II clinical trial of 49 patients with oligometastatic NSCLC demonstrated an eight-month increase in progression-free survival (PFS) in patients who underwent local consolidative therapy (LCT), defined as treatment with the goal to ablate or resect all residual disease using radiotherapy or surgery, for all disease sites, compared with patients who underwent only maintenance or observation (median PFS, 11.9 vs 3.9 months; p = 0.005) [8].

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