Elsevier

Thoracic Surgery Clinics

Volume 18, Issue 4, November 2008, Pages 403-415
Thoracic Surgery Clinics

Neoadjuvant Therapy for Resectable Non–Small Cell Lung Cancer with Mediastinal Lymph Node Involvement

https://doi.org/10.1016/j.thorsurg.2008.07.004Get rights and content

Survival outcomes of patients with stage IIIA non–small cell lung cancer (NSCLC) with mediastinal lymph node involvement (N2 disease) have been poor when treated with surgery alone. Numerous studies have investigated induction chemotherapy, radiation, and chemoradiation to attempt to improve outcome in this high-risk population. The appropriate application and sequence of these treatments is still the subject of ongoing study. Surgical resection appears to have the greatest benefit in patients who have decreased mediastinal involvement following induction therapy, although the type of surgical resection (pneumonectomy or lesser resection) impacts morbidity and mortality risks after induction therapy. Molecularly targeted agents are also being studied as a potential induction therapy for use in the treatment of stage IIIA disease.

Section snippets

Mediastinal staging

The prognosis and optimal treatment of patients diagnosed with NSCLC depends on accurate staging [2], [5], [6], [7]. Nodal involvement can be determined by either noninvasive or invasive measures. Although on computerized tomography (CT) imaging a lymph node larger than 1 cm in diameter is considered abnormal, studies have shown that size is not a reliable predictor of tumor involvement [8], [9]. Toloza and colleagues [10] reported in a meta-analysis of 3438 patients imaged with CT a

Induction chemotherapy

Numerous nonrandomized phase II trials using induction chemotherapy can be found in the literature. In a summary by Meko and Rusch [14], chemotherapy followed by surgery in highly selected patients with and without postoperative radiation therapy suggested there may be an improvement in resectability and possibly improved survival over single-modality therapy. Martini and colleagues [15] published their experience with the administration of two to three cycles of cisplatin, vindesine or

Induction chemotherapy with third-generation agents

Phase II trials evaluating the efficacy of third-generation chemotherapy agents have been performed with varying results. Results of studies evaluating induction chemotherapy with third-generation agents are summarized in Table 2.

The Swiss Group for Clinical Cancer Research (SAKK) enrolled 90 patients in a nonrandomized trial to receive three cycles of cisplatin and docetaxel followed by surgery. Postoperative radiation was given to 33 patients with positive surgical margins, with involvement

Induction chemoradiotherapy

Given that concurrent chemoradiation is superior to sequential therapy in the definitive management of unresectable locally advanced NSCLC [29], [30], a combined-modality approach has been investigated in the neoadjuvant setting for potentially resectable locally advanced NSCLC. Results of trials evaluating induction chemoradiotherapy are summarized in Table 3.

The phase II Southwest Oncology Group (SWOG) 8805 study was one of the first trials looking at induction chemoradiotherapy. This study

Role of surgery

The appropriate selection of patients for surgery following neoadjuvant therapy continues to be a challenge for all specialists who deal with locally advanced NSCLC. Concern about increased morbidity and mortality of resection following induction therapy emphasizes the importance of selecting patients who may benefit from surgical intervention [32], [33]. Accurate restaging is essential to identify disease refractory to induction therapy in order to reduce the operative risk of surgery in

Induction therapy with molecularly targeted agents

A number of molecularly targeted agents have now been shown to prolong life for patients with NSCLC in the setting of advanced disease. These include monoclonal antibodies as well as a small molecule tyrosine kinase inhibitor. A large number of new targeted agents are in various stages of testing and clinical development. Bevacizumab, a monoclonal antibody targeted against vascular endothelial growth factor (VEGF), has been shown to prolong survival in combination with chemotherapy for patients

Summary

The optimal treatment for stage IIIA (N2) NSCLC remains controversial. Numerous studies with induction chemotherapy or chemoradiotherapy show that both approaches in the neoadjuvant setting are feasible. Outcomes following induction therapy have been associated with mediastinal nodal response, with residual mediastinal involvement a negative predictor of survival. Appropriate selection of patients to undergo resection following induction therapy is critical. Lobectomy may be safely performed

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