Prognostic Impact and Recurrence Pattern of KRAS G12C Mutation in Surgically Resected Non-Small Cell Lung Cancer

The effect of KRAS mutant subtypes on the outcome and recurrence pattern of patients with nonadvanced lung cancer remains controversial. This study aimed to broadly elucidate the oncologic characteristics of G12C mutation in resected non-small cell lung cancer (NSCLC).

A total of 18,509 stage I-III NSCLC patients who received surgical resection and genetic assay were retrospectively enrolled. Paired cases of KRAS mutation and wild type were formed by propensity score matching. The Kaplan-Meier and Fine-Gray methods were used to describe the survival and recurrent differences. Multivariable analyses were used to control for confounders.

KRAS mutation was detected in 1139 patients (6.2%), including 362 G12C and 777 non-G12C mutations. The G12C group showed more male, smoker, and high-grade dominated adenocarcinoma cases than KRAS wild type and non-G12C groups. In the matched cohort, multivariable analyses revealed that G12C mutation was a high-risk factor for time-to-relapse (hazard ratio [HR] _{vs wild type}, 1.30, P = .018; HR _{vs non-G12C}, 1.45, P = .002), lung cancer-specific survival (HR _{vs wild type}, 1.49, P = .004; HR _{vs non-G12C}, 1.45, P = .009), and overall survival (HR _{vs wild type}, 1.39, P = .009; HR _{vs non-G12C}, 1.30, P = .048), independent of clinicopathologic characteristics. G12C-mutated tumors were more likely to relapse rapidly, as well as to develop distant and extrathoracic metastatic recurrences. Both G12C and non-G12C mutations resulted in shorter postrecurrence survival.

KRAS G12C mutation is associated with adverse outcomes and aggressive recurrence patterns for resected NSCLC. Effective perioperative therapies and close postoperative monitoring strategies might be implemented in this population.