We finally screened 1246 patients diagnosed with pulmonary LCNEC; their demographic and tumor characteristics are presented in Table 1. The median survival times in the LCSD and total-patients groups were 10 and 16 months, respectively. The 937 patients who died comprised 796 who died from LCNEC and 141 who died from other causes, which indicates that competing events constituted 15% of the deaths.
The largest age group of the diagnosed total patients comprised those aged 60–80 years, followed by patients younger than 60 years, with patients older than 80 years accounting for only a small proportion. Most of the patients who died were white (84.51%), and male deaths predominated in both the total-patient (54.98%) and LCSD (57.66%) groups. Regarding the tumor origin, in 89% of the patients it was located in a lung lobe, and only 1.36% of patients had overlapping lesions of the lung. AJCC stages I and IV accounted for 37.4% and 32.1% of the total patients, respectively. The proportions of patients with TNM stages T1 and T2 were 27.69% and 38.28%, respectively. TNM stage N0 patients accounted for 52.33%, while lymph-node-positive patients accounted for 38.84%. In addition, 56.02% and 52.17% of patients received surgery and chemotherapy, respectively, whereas only 13.88% received radiotherapy.
The multivariate analysis indicated that there were too few competing events to allow M-stage patients to be included in the calculations. The Cox regression analysis indicated that the independent prognostic factors for pulmonary LCNEC were sex (P = 0.0017, HR = 0.809, 95%CI = 0.708–0.923), AJCC stage II (P<0.0001, HR = 2.629, 95%CI = 1.826–3.784), AJCC stage III (P<0.0001, HR = 2.111, 95%CI = 1.560–2.856), AJCC stage IV (P<0.0001, HR = 4.000, 95%CI = 3.023–5.293), TNM stage T4 (P = 0.0043, HR = 1.396, 95%CI = 1.111–1.756), TNM stage N3 (P = 0.0031, HR = 1.499, 95%CI = 1.146–1.961), lymph-node status (P = 0.0008, HR = 1.565, 95%CI = 1.206–2.032), surgery (P<0.0001, HR = 0.569, 95%CI = 0.445–0.726), and chemotherapy (P<0.0001, HR = 0.378, 95%CI = 0.323–0.441).
The SD model analysis showed that the independent prognostic factors were sex (P = 0.0043, HR = 0.793, 95%CI = 0.676–0.930), AJCC stage II (P<0.0001, HR = 2.455, 95%CI = 1.615–3.730), AJCC stage III (P = 0.0004, HR = 1.878, 95%CI = 1.324–2.663), AJCC stage IV (P<0.0001, HR = 3.495, 95%CI = 2.555–4.779), TNM stage T4 (P = 0.0362, HR = 1.334, 95%CI = 1.019–1.748), TNM stage N2 (P = 0.0131, HR = 1.403, 95%CI = 1.074–1.833), TNM stage N3 (P = 0.0395, HR = 1.395, 95%CI = 1.016–1.916), lymph-node status (P = 0.0012, HR = 1.626, 95%CI = 1.211–2.183), surgery (P = 0.0004, HR = 0.619, 95%CI = 0.474–0.808), and chemotherapy (P<0.0001, HR = 0.521, 95%CI = 0.427–0.636).
Finally, the CS model analysis showed that the independent prognostic factors were sex (P = 0.0012, HR = 0.789, 95%CI = 0.683–0.911), AJCC stage II (P<0.0001, HR = 2.905, 95%CI = 1.953–4.321), AJCC stage III (P<0.0001, HR = 2.217, 95%CI = 1.593–3.086), AJCC stage IV (P<0.0001, HR = 4.609, 95%CI = 3.390–6.265), TNM stage T2 (P = 0.0429, HR = 1.238, 95%CI = 1.007–1.522), TNM stage T4 (P = 0.001, HR = 1.518, 95%CI = 1.184–1.947), TNM stage N2 (P = 0.012, HR = 1.337, 95%CI = 1.066–1.677), TNM stage N3 (P = 0.0015, HR = 1.579, 95%CI = 1.190–2.093), lymph-node status (P = 0.0003, HR = 1.707, 95%CI = 1.275–2.285), surgery (P<0.0001, HR = 0.544, 95%CI = 0.418–0.709), and chemotherapy (P<0.0001, HR = 0.372, 95%CI = 0.314–0.440).
The results from the three types of model analysis demonstrate that sex, AJCC stage, TNM stage T4, TNM stage N3, lymph-node status, surgery, and chemotherapy are independent risk factors for the prognosis of pulmonary LCNEC (see Table 3).