Does Lung Adenocarcinoma Subtyping Offer Clinical Benefits? A Population-Based Study from Sweden

Abstract

Purpose: Classification of lung adenocarcinoma into subtypes is relatively recent and not universally practiced. Consequently, large representative studies describing clinical outcomes are rare, failing to pervasively present advantages of subtyping. We describe the situation in Sweden with focus on survival.Methods: Patient data were obtained from the Swedish cancer registry from 2005 to 2021 accounting for 1418 patients, less than 5% of the reference group 'adenocarcinoma not otherwise specifed (NOS)'. Non-parametric survival estimates were calculated using the Kaplan-Meier method and testing for linear consistency using Weibull modelling.Results: Survival was generally better for women compared to men and this was most prominent for early-stage cancers. Female 5-year survival decreased in order, lepidic (59%), papillary (51%), invasive mucinous (46%), colloid (36%) and adenocarcinoma NOS (24%). Male 5-year survival for lepidic (46%) and colloid subtypes (22%) was significantly lower than female survival. Survival slopes for T1, T2, N0, M0 cases of lepidic, papillary and adenocarcinoma NOS were almost linear, in agreement with Weibull modelling k-values of 1.00 or slightly higher, impling that mortality increased slowly with time.Conclusions: The results showed female survival advantage for all adenocarcinoma subtypes. Survival in T1 and T2 classes with N0 and M0 for lepidic, papillary and adenocarcinoma NOS was close to linear, suggesting that patients are homogeneously diagnosed and treated. Survival benefits of lepidic and papillary subtypes over adenocarcinoma NOS give justification for adenocarcinoma subclassification, and also an independent validation of the WHO 2021 adenocarcinoma grading classification specifying lepidic and papillary subtypes.