Histological type predicts mediastinal metastasis and surgical outcome in resected cN1 non-small cell lung cancer

Non-small cell lung cancer (NSCLC) patients at cN1 have unfavorable outcomes. It has been reported that a substantial proportion of cN1 patients have occult mediastinal disease, and treatment guidelines suggest invasive preoperative mediastinal evaluation. However, the population that would most benefit from invasive staging has not been defined. The aims of this study are to identify factors predicting mediastinal metastasis and outcomes in cN1 NSCLC patients to select appropriate candidates for invasive mediastinal evaluation.

We retrospectively studied 164 patients with radiologically diagnosed cN1 NSCLC. Clinicopathological factors including radiological nodal findings were reviewed. Factors predicting the pN2 status, disease-free survival (DFS), and overall survival (OS) were investigated.

Among 164 patients with cN1 disease, pN2 was diagnosed in 43 (26.4%). This pN2 subgroup included a higher proportion of cases with adenocarcinoma (AD) histology than the pN0/1 subgroup (60.5 vs. 38.8%, p = 0.012). Logistic regression analyses revealed AD as an independent predictor of the pN2 status, while radiological nodal findings were unrelated. Cox regression analyses identified lower preoperative serum CEA, non-AD, and pN0/1 status as favorable factors of DFS and adjuvant therapy to be associated with OS. Five-year DFS was much lower in the pN2 subgroup than the pN0/1 subgroup of AD patients (p < 0.001), while DFS was independent of pN status in non-AD patients.

Adenocarcinoma is predictive of pN2 and poor prognosis in radiologically diagnosed cN1 NSCLC. Accurate mediastinal staging may be more beneficial for prognoses and optimal treatment planning in NSCLC patients with AD histology.