This manuscript was able to assess some treatment-related factors because SEER-18 does contain some variables related to radiation and surgery. Patients receiving pre-operative radiation were excluded because it was felt that this treatment could obscure/improve histolopathologic variables. Because SEER-18 does not contain information pertaining to chemotherapeutic treatment, we deliberately decided to separately assess a surgical sub-group of patients with tumors 4 cm or less without nodal involvement because these patients would be unlikely to receive chemotherapy (17, 18). Furthermore, we decided to investigate LCSS as well in this group of early-stage patients because of their relatively high likelihood of surviving lung cancer and possibly succumbing to other smoking-related causes. Worse OS and LCSS were consistently noted after a pneumonectomy despite multivariable analyses that accounted for histopathologic, patient, and tumor location variables. The adverse survival of patients undergoing a pneumonectomy was identified in recent retrospective study that demonstrated that that the lower survival may be due to an increased risk of distal metastases (19). Although the immune effects of a larger lung cancer procedures such as pneumonectomy as compared to (bi)lobectomy and sub-lobar resections is not known, it has been shown that transthoracic surgery for esophageal cancer as compared to smaller and less invasive surgical procedures (gastrectomy for cancer and cholecystomy for benign gallstones) has been associated with a transient immunosuppression (increased T-cell apoptosis and decreased T-cell cytokine production) during post-operative days 1–3 (20). Interestingly, a different research group noted that both transhiatal and transthoracic esophagectomies were associated with reduced TH1-type cytokine production on post-operative day 1, but depression of Th2-type cytokine was more profound with the latter procedure (21). In both surgical populations, the number of nodes examined was strongly correlated with OS and LCSS and was similarly noted in a past SEER analysis (22). The better outcomes associated with an increasing number of nodes examined may be due to the removal of microscopic disease that may or may not be recognized (especially in the ESR group) by routine pathologic methods (23), but because there is no OS with mediastinal lympadenectomy as compared to nodal sampling (24), one might infer that the beneficial effects of lymph node examination may be due to upstaging cancers that would otherwise be classified as node negative. Post-operative radiation was associated with poorer OS and LCSS. Although past retrospective analyses have demonstrated a possible survival benefit for radiation therapy in patients with N2 disease (25, 26), others have not (27). However, there has been general agreement that post-operative radiation results in a survival decrement in patients with N0 and N1 disease (25, 26). A recent retrospective investigation demonstrated that there was an OS benefit for post-operative radiation therapy for patients who experience a positive resection margin for all nodal stages (28). We would assume that the patients who receive post-operative radiation therapy for nodal stages N0–N1 during the years of our study had a positive margin, but SEER does not have information concerning margin status, and our results show a strongly negative effect of radiation on OS and LCSS in the surgical patients. Although there may be negative selection factors (i.e., positive margin, lymphatic, and/or vascular invasion) in the patients receiving radiation, it may be that radiation therapy has no efficacy and could possibly only have deleterious effects in the post-operative setting, especially in those with N0–N1 disease.