Patterns of Relapse of N2 Nonsmall-cell Lung Carcinoma Patients Treated with Preoperative Chemotherapy: Should Prophylactic Cranial Irradiation Be Reconsidered?

Background: Although it induces a relevant reduction in the risk of both visceral metastases and locoregional recurrences, the combination of chemotherapy and surgery only marginally improves the survival of patients with Stage IIIA(N2) (International Union Against Cancer staging and classification system) nonsmall-cell lung carcinoma (NSCLC). The purpose of the current study was to analyze the patterns of relapse in these patients.

Methods: In this study, the authors compared the patterns of relapse in 81 patients with clinically detectable N2 NSCLC who had been treated with preoperative chemotherapy with the relapse patterns of 186 comparable patients who had been treated with primary surgery. Clinically detectable N2 (cN2) denotes mediastinal lymph node enlargement on computed tomography scan, which then is confirmed by mediastinoscopy.

Results: Overall 20% of patients developed a locoregional recurrence. Chemotherapy decreased the risk of visceral metastasis as 28% of the patients preoperatively treated and 38%of those not treated with preoperative chemotherapy presented a visceral metastasis (P < 0.05). Preoperative chemotherapy and adenocarcinoma subtypes were associated with a higher rate of brain metastasis (P < 0.05). Thirty-two percent of the patients treated preoperatively and 18% of those not treated with preoperative chemotherapy presented a brain metastasis (P < 0.05), which was isolated in 22% and 11% of the patients, respectively (P < 0.05).

Conclusion: The current study found that preoperative chemotherapy for cN2 decreases the risk of visceral metastasis but is associated with a high rate of isolated brain metastases. Prophylactic cranial irradiation may need to be reinvestigated in clinical trials, especially in patients who present with an adenocarcinoma.