Temporal and regional distribution of initial recurrence site in completely resected N1-stage II lung adenocarcinoma: The effect of postoperative adjuvant chemotherapy

Objectives: Understanding the timing and pattern of cancer recurrence is essential to explain the causes of treatment failure. We investigated the recurrence pattern and rate over time in patients with completely resected N1-stage II lung adenocarcinoma. Materials and methods: We retrospectively reviewed the medical records of 333 patients who underwent complete surgical resection for N1-stage II lung adenocarcinoma. Results: The median recurrence-free survival (RFS) was 38.8 months and the 5-year RFS rate was 39.6%. Left-sided tumors, large tumor size, and lymph node (LN) ratio higher than 0.15 were significantly correlated with a worse RFS, whereas female sex, direct LN involvement, and adjuvant chemotherapy were significantly correlated with a better RFS. Among the 182 patients who experienced recurrences, 46 (25.3%) had only loco-regional recurrences and 136 (74.7%) had distant metastases. The organs most commonly involved in initial recurrence were the lungs (n = 89, 48.9%), followed by bone (n = 41, 22.5%) and the brain (n = 38, 20.9%). The recurrence hazard curve for the entire study population demonstrated a similarly shaped and sized initial and second peak at 15 and 23 months, and a third smaller peak during the fourth year. The recurrence hazard curve of patients who received adjuvant chemotherapy exhibited a more delayed and smaller first peak than those who did not receive adjuvant chemotherapy. The patients treated with adjuvant chemotherapy had a lower rate of distant metastasis (p = 0.037); adjuvant chemotherapy had no effect on brain metastasis (p = 0.640). Conclusion: In the present cohort, the hazard curves suggested that bone and brain recurrences exhibited an earlier first peak, while lung recurrences presented later. Adjuvant chemotherapy not only reduced the recurrence hazard but also delayed the recurrence and altered the pattern of recurrence. However, these results need to be confirmed in a prospective study.