Retrospective study of the prognostic impact of common molecular alterations in resected lung adenocarcinoma

Whether gene mutations can be integrated into the forthcoming 10^th Edition TNM staging system is of interest. A retrospective study at Fudan University Shanghai Cancer Center (China) investigated the stage-specific prognostic impact of alterations in the major driver genes TP53 (oncogenic/likely oncogenic), EGFR mutation (L858R, exon 19 deletion), KRAS mutations (codons 12, 13, or 61), and ALK fusions. A total of 5,839 patients were included. EGFR mutations were found in 54.7%, TP53 mutations in 29.9%, KRAS mutations in 6.8%, and ALK fusions in 4.6%. Overall survival (OS) was significantly better among patients with stage I EGFR-mutated tumors and stages III-IV ALK fusion-positive tumors, whereas patients with stage I TP53 mutated tumors and KRAS mutated tumors had significantly worse OS. Multivariable analyses confirmed the OS associations with TP53-mutated tumors (stage I HR=2.49), KRAS-mutated tumors (stage I HR= 1.57), and EGFR-mutated tumors (sateg I HR=0.59). In the upstaging/downstaging analysis, patients with TP53- or KRAS-mutated stage IA disease exhibited OS comparable to stage IB, supporting an upstaging potential. Conversely, patients with stage III-IV ALK fusions showed OS comparable to stage II, supporting a downstaging potential. The authors conclude that these results suggest that common molecular alterations in lung cancer exhibit prognostic value within specific stages and hold the potential to modify the current staging system.