Microscopic residual disease after resection for lung cancer: a multifaceted but poor factor of prognosis

Background: Many studies focus on bronchial microscopic residual disease (R1) after resection for lung cancer, although R1 also concerns vascular and soft tissues. Our purpose was to study the R1 prognosis at different resection margins and to compare it with the prognosis for those having complete resection (R0).

Methods: We reviewed the clinical records of 4,026 patients from two centers who underwent surgery in view of cure. Despite perioperative frozen section, 216 patients (5.4%) proved R1 and were classified into seven types according to R1 anatomic site: bronchus, peribronchus, great vessels and atrium, mediastinum and pericardium, chest wall, lung tissue, and lymph nodes. Patients who were classified as R0 and R1 were compared, and R1 patients were further studied according to R1 margins.

Results: Frequency of R1 increased with the T and N values and type of resection (lobectomies, 3.3% [70 of 2,041 patients]; pneumonectomies, 8.8% [126 of 1,308 patients]; p < 10(-6)). Five-year survival rates for R1 patients were lower than those for R0 patients (20% versus 46%; p < 10(-6)), and were not modified by the degree of T and N involvement or adjuvant therapy, but were better in bronchial and peribronchial (48.4% of R1 patients) than in extrabronchial R1 (26.3% versus 15.6%; p = 0.023). Multivariate analysis confirmed R1 to be an independent factor of poor prognosis (p = 0.0008), after N, T, and age.

Conclusions: Long-term survival is possible in case of an R1 margin, but 5-year survival rates are jeopardized. Poor efficacy of adjuvant therapy and global outcome indicate advanced disease or reflect tumor cell aggressiveness, rather than surgical insufficiency, when prevention of R1 margins is guided by frozen-section examination and scrupulously respected.