Uncertain Resection in Lung Cancer: A Comprehensive Review of the International Association for the Study of Lung Cancer Classification

Objective: We explored the impact of uncertain resection in lung cancer on overall survival and disease-free survival. Methods: We performed an exhaustive literature review of all studies comparing prognosis after resection according to the IASLC classification, from the PubMed, Cochrane, MEDLINE, and Google Scholar databases. Results: Overall, 68 original studies were included, of which 67 were retrospective and 1 was prospective, with 81 785 patients included over 46 years. R(un) reclassification was mostly caused by a lack of hilar or mediastinal node dissection, or because of metastasis in the highest node. R(un) is a strong factor for higher recurrence and mortality, while its effects seem limited in early stages. Carcinoma in situ at bronchial margin resection (CIS BRM) does not show an effect on survival, while positive pleural cytology (Cy+) and positive highest mediastinal lymph node (HMLN+) appear to be highly predictive of recurrence and death. Discussion: The R(un) classification of the IASLC appears highly relevant, especially in locally advanced stages IIb-IIIA, and helps to discriminate patients with poor prognosis despite being classified as R0 in the UICC classification. Conclusions: The use of this more precise classification would allow for better stratification of recurrence risk and more effective use of adjuvant therapies. Cy+ patients should receive adjuvant chemotherapy, while CIS BRM patients could likely benefit from endoscopic surveillance to detect local recurrences. HMLN+ patients should be considered at high risk of recurrence, and adjuvant radio-chemotherapy should be considered.