Histologic Grade 3 in Stage 1A Lung Adenocarcinoma: Survival Risks Comparable to Stage 1B

Early stage NSCLC presents a significant risk of recurrence despite surgical resection. The International Association for the Study of Lung Cancer-proposed histologic grading system identifies high-grade tumors (≥20% solid, micropapillary, or complex glandular patterns) as a potential prognostic tool. This study evaluates the prognostic significance of histologic grade 3 within stage IA non-mucinous adenocarcinoma and its comparability to stage IB.

We retrospectively analyzed 729 patients with stage I non-mucinous adenocarcinoma who underwent surgical resection (2010-2017). Tumors were graded per the International Association for the Study of Lung Cancer system. Kaplan-Meier survival curves and Cox proportional hazards models assessed overall survival (OS) and disease-free survival (DFS).

Stage IA grade 3 tumors demonstrated significantly worse OS and DFS compared with grade 1 and 2 tumors (p < 0.001). Survival outcomes for stage IA grade 3 tumors were comparable to stage IB (p = 0.677 for OS, p = 0.248 for DFS). Stage IA grade 3 tumors also demonstrated a trend toward worse survival than stage IB grades 1 and 2. Grade 3 tumors exhibited sufficient risk stratification power, comparable to the already well-established risk factor of pleural invasion. Tumors with any high-grade patterns (>0%) had poorer survival than those without, but risks were less pronounced than the 20% cutoff.

Histologic grade 3 in stage IA identifies high-risk tumors comparable to stage IB, highlighting its potential for refining staging criteria and guiding adjuvant therapy. Validation studies are needed to confirm these findings.