The presence of micropapillary and/or solid subtypes is an independent prognostic factor for patients undergoing curative resection for stage I lung adenocarcinoma with ground-glass opacity

Abstract

Background: Non-predominant or even minimal micropapillary and/or solid (MP/S) subtypes have been reported to exert an unfavorable prognostic influence on surgically resected lung adenocarcinoma (ADC). Currently, there is a lack of evidence to demonstrate that high-grade pathological subtypes, including MP/S components, impact the prognosis of patients with surgically resected lung ADCs with ground-glass opacity (GGO). In this investigation, we explored the prognostic implications of minimal MP/S components in lung ADCs with GGO.

Methods: A retrospective cohort study was conducted on 1,004 consecutive patients undergoing curative resection for pathologic stage (p-stage) I lung ADCs featuring GGO on computed tomography (CT) scans between January 2014 and December 2016. Tumors were categorized into MP/S positive (MP/S⁺) group and MP/S negative (MP/S^-) group. MP/S⁺ tumors were defined when MP/S subtypes constituted ≥1% of the entire tumor. The prognostic impact of MP/S subtypes was evaluated using Kaplan-Meier analysis, Cox proportional hazard model and restricted cubic spine (RCS) model.

Results: A total of 86 (8.6%) cases with MP/S⁺ tumors and 918 (91.4%) cases with MP/S^- tumors were identified. The solid component tumor diameter and pathological invasive tumor size of MP/S⁺ tumors were both significantly larger than that of MP/S^- tumors (13.0 vs. 4.0 mm, P<0.001, and 18.0 vs. 10.0 mm, P<0.001, respectively). After a median follow-up of 7.3 years, the presence of MP/S components was significantly associated with decreased RFS (5-year RFS, MP/S⁺ 88.3% vs. MP/S^- 97.4%; P<0.001; HR =1.02). The presence of a histologic lepidic (Lep) component demonstrated a prognostic advantage in both MP/S^- (5-year RFS, MP/S^-Lep+ 98.0% vs. MP/S^-Lep- 95.3%; P=0.01; HR =0.89) and MP/S⁺ subgroups (5-year RFS, MP/S⁺Lep+ 93.4% vs. MP/S⁺Lep- 83.2%; P=0.10; HR =0.84). MP/S⁺ components ≥5% were the only tumor-related factor that independently affected RFS [hazard ratio (HR) =1.77; 95% confidence interval (CI): 1.07-2.94] according to multivariate analysis. There was a progressively negative impact of the proportion of MP/S subtypes on RFS as illustrated by RCS model.

Conclusions: The presence of MP/S patterns in stage I GGO-featured lung ADCs exhibit significant prognostic value and may have implications for tailored postoperative treatment and surveillance strategies, especially when the proportion exceeds 5% of the entire tumor.

Keywords: Lung cancer; adenocarcinoma (ADC); ground-glass opacity (GGO); micropapillary; solid.

Figure 1

Kaplan-Meier survival curves of RFS according to the presence of MP/S subtypes in (A) all p-stage I ADCs, (B) tumors ≤1.0 cm, (C) tumors >1.0 to 2.0 cm, and (D) tumors >2.0 to 3.0 cm. −, negative; +, positive. MP/S, micropapillary and/or solid; RFS, recurrence-free survival; p-stage, pathologic stage; ADC, adenocarcinoma.

Figure 2

Kaplan-Meier survival curves of (A) RFS and (B) OS according to four subgroups of MP/S subtypes. −, negative; +, positive. MP, micropapillary; S, solid; RFS, recurrence-free survival; OS, overall survival.

Figure 3

Kaplan-Meier survival curves of RFS according to the presence of MP/S and Lep subtypes in (A) all p-stage I ADCs and (B) acinar- or papillary-predominant ADCs. −, negative; +, positive. MP/S, micropapillary and/or solid; Lep, lepidic; RFS, recurrence-free survival; p-stage, pathologic stage; ADC, adenocarcinoma.

Figure 4

Association of the proportion of MP/S subtypes with RFS. HR is indicated by the solid line and 95% CI by shaded areas. HR, hazard ratio; CI, confidence interval; MP/S, micropapillary and/or solid; RFS, recurrence-free survival.