Lung cancer survival trends and prognostic factors: A 26-year population-based study in Girona Province, Spain

Background: Lung cancer (LC) is Europe's primary cause of cancer-related mortality largely due to its historically low survival rates. The aim of this study was to analyze 26-year survival trends in the province of Girona, Spain, and to identify key prognostic factors. Methods: Population-based study of LC cases collected between 1994 and 2019, with follow-up until December 31, 2021. Variables included date of diagnosis, sex, age, histology, and tumor stage (the latter since 2010). Diagnosis dates were categorized into three periods (1994-2002, 2003-2011, and 2012-2019). Multivariate flexible parametric models, incorporating age as a non-linear, time-varying covariate, were used to analyze net survival (NS) and trends. Annual absolute change in survival (AAC_S) was calculated using 3-year NS. Results: The analysis of 9,113 LC cases showed a NS improvement between the first and last period (7.1 months (95 %CI: 6.5;7.6) to 8.5 months (95 %CI: 7.9;9.1)). Squamous cell carcinoma (NSC-SCC) showed the greatest improvement with an AAC_S of 0.32 % (95 % CI: 0.21; 0.43), while survival for non-small cell lung cancer not otherwise specified declined (AAC_S of- 0.19 % (95 %CI:-0.26;-0.12)). Prognostic analysis of the 3,642 cases (2010-2019) indicated a lower LC death risk for adenocarcinoma and NSC-SCC compared to LC not otherwise specified (HR 0.52 and 0.62, respectively). Increasing tumor stage correlated with higher LC mortality risk (1.8-, 4.0-, and 10.1-fold increase for stage II, III, and IV, respectively, compared to stage I). Conclusions: LC survival has notably improved, particularly for NSC-SCC. Survival is influenced by sex, age, date of diagnosis, tumor histology and especially by stage, underscoring comprehensive data collection's importance.