Stage IIIA NSCLC Treatment
Small retrospective series of radiation therapy in patients who were only clinically staged have reported 5-year survival rates of 0% to 40%, depending on T stage, total radiation dose, and other prognostic factors. Induction radiation therapy and en-bloc resection was shown to be potentially curative.
- In the preoperative setting, a dose of 45 Gy over 5 weeks is generally recommended, while a dose of approximately 61 Gy is required when using definitive radiation therapy as the primary modality.[36,37]
- Retrospective case series have reported complete resection was achieved in only 64% of T3, N0 tumors and 39% of T4, N0 tumors.
- Two large, prospective, multicenter phase II trials have evaluated induction chemoradiation therapy followed by resection.[39,40]
- In the first trial (NCT00002642), 110 eligible patients were enrolled with mediastinoscopy negative, clinical T3-4, N0-1 tumors of the superior sulcus. Induction treatment was two cycles of etoposide and cisplatin with 45 Gy of concurrent radiation therapy.
- The induction regimen was well tolerated and only five participants had grade 3 or higher toxic effects.
- Induction chemoradiation therapy could sterilize the primary lesion. Induction therapy was completed by 104 patients (95%). Of the 95 patients eligible for surgery, 88 (80%) underwent thoracotomy, two (1.8%) died postoperatively, and 83 (76%) had complete resections.
- Pathologic complete response or minimal microscopic disease was seen in 61 (56%) resection specimens. Pathologic complete response led to better survival than when any residual disease was present (P = .02).
- Five-year survival was 44% for all patients and 54% after complete resection, with no difference between T3 and T4 tumors. Disease progression occurred mainly in distant sites.
- In the second trial, 75 patients were enrolled and treated with induction therapy with mitomycin C, vindesine, and cisplatin combined with 45 Gy of radiation therapy. Fifty-seven patients (76%) underwent surgical resection, and complete resection was achieved in 51 patients (68%).
- There were 12 patients with pathologic complete response.
- Major postoperative morbidity, including chylothorax, empyema, pneumonitis, adult respiratory distress syndrome, and bleeding, was observed in eight patients. There were three treatment-related deaths.
- The disease-free and OS rates at 3 years were 49% and 61%, respectively; at 5 years, they were 45% and 56%, respectively.[Level of evidence: 3iiiDi]
Standard Treatment Options for Tumors That Invade the Chest Wall (T3, N0 or N1, M0)
Selected patients with bulky primary tumors that directly invade the chest wall can obtain long-term survival with surgical management provided that their tumor is completely resected. Radical surgery, including chest wall resection, may result in a 5-year survival rate of up to 50%. In two small case series of 97 and 104 patients, respectively, the 5-year survival rates of patients with completely resected T3, N0, M0 disease were 44.2% and 67.3%, T3, N1, M0 disease 40.0%, and T3, N2, M0 disease 6.2% and 17.9%.[41,42][Level of evidence: 3iiiDi] In a case series of 309 patients treated at three centers, patients who underwent en bloc resection had superior outcomes compared with patients who underwent extrapleural resections (60.3% vs. 39.1%; P = .03).[Level of evidence: 3iiiDi] Adjuvant chemotherapy is recommended and radiation therapy is reserved for cases with unclear resection margins. Survival rates were lower in patients who underwent incomplete resection and had mediastinal lymph node involvement. Combined modality approaches have been evaluated to improve ability to achieve complete resection.