Persistent increase and improved survival of stage I lung cancer based on a large-scale real-world sample of 26,226 cases

Abstract

Background: Lung cancer prevails and induces high mortality around the world. This study provided real-world information on the evolution of clinicopathological profiles and survival outcomes of lung cancer, and provided survival information within stage I subtypes.

Methods: Patients pathologically confirmed with lung cancer between January 2009 and December 2018 were identified with complete clinicopathological information, molecular testing results, and follow-up data. Shifts in clinical characteristics were evaluated using χ2 tests. Overall survival (OS) was calculated through the Kaplan-Meier method.

Results: A total of 26,226 eligible lung cancer patients were included, among whom 62.55% were male and 52.89% were smokers. Non-smokers and elderly patients took increasingly larger proportions in the whole patient population. The proportion of adenocarcinoma increased from 51.63% to 71.80%, while that of squamous carcinoma decreased from 28.43% to 17.60%. Gene mutations including EGFR (52.14%), KRAS (12.14%), and ALK (8.12%) were observed. Female, younger, non-smoking, adenocarcinoma patients and those with mutated EGFR had better survival prognoses. Importantly, this study validated that early detection of early-stage lung cancer patients had contributed to pronounced survival benefits during the decade. Patients with stage I lung cancer, accounted for an increasingly considerable proportion, increasing from 15.28% to 40.25%, coinciding with the surgery rate increasing from 38.14% to 54.25%. Overall, period survival analyses found that 42.69% of patients survived 5 years, and stage I patients had a 5-year OS of 84.20%. Compared with that in 2009-2013, the prognosis of stage I patients in 2014-2018 was dramatically better, with 5-year OS increasing from 73.26% to 87.68%. Regarding the specific survival benefits among stage I patients, the 5-year survival rates were 95.28%, 93.25%, 82.08%, and 74.50% for stage IA1, IA2, IA3, and IB, respectively, far more promising than previous reports.

Conclusions: Crucial clinical and pathological changes have been observed in the past decade. Notably, the increased incidence of stage I lung cancer coincided with an improved prognosis, indicating actual benefits of early detection and management of lung cancer.

Figure 1

Evolutions in clinicopathologic characteristics of lung cancer patients from 2009 to 2018: (A) sex; (B) smoking history; (C) histology; (D) stage; (E) surgery; and (F) age. LUAD: Lung adenocarcinoma; LUSC: Lung suamous cell carcinoma; SCLC: Small cell lung cancer.

Figure 2

Overall survival curves by clinicopathologic characteristics: (A) all patients; (B) sex; (C) age; (D) smoking history; (E) histology; (F) stage; (G)surgery; and (H) diagnosis year. CI: Confidence interval; LUAD: Lung adenocarcinoma; LUSC: Lung suamous cell carcinoma; NA: Not applicable; SCLC: Small cell lung cancer. Dashed lines represent the median survival time.

Figure 3

Insights into finer stage I lung cancer subtypes including IA1, IA2, IA3, and IB (A) incidence of finer stage I subtypes among whole patient population; (B) overall survival curves of finer stage I subtypes.

Figure 4

Prevalence of driver mutations in critical genes for patients with lung cancer in adenocarcinoma and squamous carcinoma. Positive stands for harboring mutation, while negative stands for being wild-type. LUAD: Lung adenocarcinoma; LUSC: Lung suamous cell carcinoma; EGFR: Epidermal growth factor receptor; KRAS: Kirsten rat sarcoma viral oncogene homologue; MET: Mesenchymal-epithelial transition factor; ALK: Anaplastic lymphoma receptor tyrosine kinase; ERBB2: Erb-b2 receptor tyrosine kinase 2; BRAF: V-Raf murine sarcoma viral oncogene homolog B1; ROS1: ROS proto-oncogene 1; RET: Rearranged during transfection.

Figure 5

Overall survival curves by genomic mutations: (A) EGFR; (B) KRAS (C) MET; (D) ALK; (E) ERBB2; (F) BRAF; (G) ROS1; and (H) RET. Positive stands for harboring mutation, while negative stands for being wild-type. Dashed lines represent the median survival time. EGFR: Epidermal growth factor receptor; KRAS: Kirsten rat sarcoma viral oncogene homologue; MET : Mesenchymal-epithelial transition factor; ALK: Anaplastic lymphoma receptor tyrosine kinase; ERBB2: Erb-b2 receptor tyrosine kinase 2; BRAF : V-Raf murine sarcoma viral oncogene homolog B1; ROS1: ROS proto-oncogene 1; RET: Rearranged during transfection.