Patients with stage IIIA NSCLC are a heterogenous group. Patients may have metastases to ipsilateral mediastinal nodes, potentially resectable T3 tumors invading chest wall, or mediastinal involvement with metastases to peribronchial or hilar lymph nodes (N1). Presentations of disease range from resectable tumors with microscopic metastases to lymph nodes to unresectable, bulky disease involving multiple nodal stations.
Patients with clinical stage IIIA-N2 disease have a 5-year overall survival rate of 10% to 15%; however, patients with bulky mediastinal involvement (i.e., visible on chest radiography) have a 5-year survival rate of 2% to 5%. Depending on clinical circumstances, the principal forms of treatment that are considered for patients with stage IIIA NSCLC are radiation therapy, chemotherapy, surgery, and combinations of these modalities.
Treatment options vary according to the location of the tumor and whether it is resectable.
Standard Treatment Options for Resected/Resectable Stage IIIA N2 NSCLC
Despite careful preoperative staging, some patients will be found to have metastases to mediastinal N2 lymph nodes at thoracotomy.
Standard treatment options for resected/resectable disease include the following:
- Neoadjuvant therapy.
- Neoadjuvant chemotherapy.
- Adjuvant therapy.
- Adjuvant chemotherapy.
- Adjuvant chemoradiation therapy.
- Adjuvant radiation therapy.
The preponderance of evidence indicates that postoperative cisplatin combination chemotherapy provides a significant survival advantage to patients with resected NSCLC with occult N2 disease discovered at surgery. The optimal sequence of surgery and chemotherapy and the benefits and risks of postoperative radiation therapy in patients with resectable NSCLC are yet to be determined.
If complete resection of tumor and lymph nodes is possible, such patients may benefit from surgery followed by postoperative chemotherapy. Current evidence suggests that lung cancer resection combined with complete ipsilateral mediastinal lymph node dissection (CMLND) is associated with a small-to-modest improvement in survival compared with lung cancer resection combined with systematic sampling of mediastinal nodes in patients with stage I, II, or IIIA NSCLC.[Level of evidence: 1iiA]
- The Cochrane Collaboration group reviewed 11 randomized trials with a total of 1,910 patients who underwent surgical interventions for early-stage (I–IIIA) lung cancer. A pooled analysis of three trials reported the following:
- Four-year survival was superior in patients with resectable stage I, II, or IIIA NSCLC who underwent resection and CMLND, compared with those who underwent resection and lymph node sampling; the hazard ratio (HR) was estimated to be 0.78 (95% confidence interval [CI], 0.65–0.93; P = .005).[Level of evidence: 1iiA]
- CMLND versus lymph node sampling was evaluated in a large randomized phase III trial (ACOSOG-Z0030). Preliminary analyses of operative morbidity and mortality showed comparable rates from the procedures.