The “N”—factor in non-small cell lung cancer: staging system and institutional reports

Abstract

Lymph node (LN) status is a highly significant component of staging of non-small cell lung cancer (NSCLC). Staging of NSCLC provides prognostic data related to the risk of recurrence as well as overall survival (1). Lymph node metastasis alters the treatment decisions, including surgical resectability and appropriateness of adjuvant interventions.According to the TNM rules, at least six lymph nodes need to be removed, three from N1 and three from N2 stations. This is the minimum requirement for a diagnosis of N0 when lymph nodes are negative (2).Currently, the 7 th edition of NSCLC staging system defines the nodal status as N0 (no nodal involvement), N1 (peribronchial, interlobar, hilar node involvement), N2 (ipsilateral nodal involvement), N3 (contralateral mediastinal, contralateral hilar or supraclavicular nodal involvement) depending only on the location of the metastatic lymph nodes and the actual definition of nodal categorization not varied in the last revision from the 6 th to the 7 th edition.Differently from other organs, in the case of lung cancer, the principle that the nodal status is based on the location of the nodal metastasis and not on the number of metastatic nodes has been maintained.The principle that raise the N staging of lung cancer on the base of the anatomic location of the involved nodes is accepted because: the lymph nodes location is easy to be determined on CT-scan or PET/CT (that is fundamental for the determination of the clinical N status), it has an high prognostic impact, and its categorization is anatomically reasonable from the perspective of a lymphatic pathway from the lung parenchyma through the hilum, the mediastinum and the supraclavicular fossa. Whereas the IASLC Staging and Prognostic FactorsCommittee was analyzing the collected database to define the above cited staging system, many authors from single institutions researched about the impact on long-term outcome of the number of involved nodes coming up to interesting results.In a recent study by Smeltzer et al. (3), "Missed intrapulmonary lymph node metastasis and survival after resection of non-small cell lung cancer", a specialized technique of intrapulmonary LN sampling is utilized to identify possible previous not detected LN metastasis; the impact on overall survival of the presence of cancer metastasis to the intrapulmonary LNs is analyzed too. In their study, the initial pathological staging after routine dissection was pN0 69%, pN1 16% and pN2 15%. After re-dissection, additional LN metastasis was found in 23% patients. This caused a lowering of the pN0 rate from 69% to 65% and an augmented rate of pN1 cases from 16% to 22%. As second end-point the above mentioned paper reported an augmented risk of death for patients with more than two missed metastatic nodes at intrapulmonary stations.Despite some limitations due to the small number of patients and the short follow-up period, the paper, like others in the recent literature (4-7), has the great value to instill two doubts: the number of metastatic LNs shoul...

Heterogeneity of stage IIIA non-small cell lung cancer—different tumours, different nodal status, different treatment, different prognosis: a narrative review

“…N1b status and single station N2 with N1 involvement (N2a2) had overlapping survival curves. The 5-year survival rates according to the cN and pN status were 60% and 75% for N0, 37% and 49% for N1, 23% and 36% for N2, and 9% and 20% for N3 nodal disease, respectively (23)(24)(25)(26). For complete resected N1-2 disease, reported 5-year survival rates were as follows: 59% in N1a, 50% in N1b, 54% in N2a1, 43% in N2a2 and 38% in N2b involvement (23).…”

Thoracic surgical challenges after neoadjuvant immunotherapy for non-small cell lung cancer: a narrative review

“…The reported 5-year survival rates according to the cN and pN status were 60% and 75% for N0, 37% and 49% for N1, 23% and 36% for N2, and 9% and 20% for N3, respectively. For patients with N1 and N2 disease, 5-year published survival rates were: 59% in N1a (single N1 station involved), 50% in N1b (multiple N1 stations involved), 54% in N2a1 (single station N2 involved without N1 status), 43% in N2a2 (single station N2 with N1 involvement) and 38% in N2b disease (multiple N2 stations involved) (6)(7)(8)(9).…”