Dose-response impact of micropapillary burden on survival and its clinical interaction with surgical extent in lung adenocarcinoma: a propensity score-matched competing risks analysis

Micropapillary (MP) components are associated with aggressive behavior in lung adenocarcinoma, but whether MP burden modifies the survival benefit of lobectomy versus sublobar resection remains undefined. We retrospectively analyzed 497 patients with MP-containing lung adenocarcinoma who underwent radical resection at a single center between January 2018 and December 2023. MP components were graded as < 5%, 5–20%, 20–40%, and > 40%. Overall survival (OS) and recurrence-free survival (RFS) were evaluated using Kaplan-Meier and Cox analyses; propensity score matching (PSM), interaction testing, Fine-Gray competing risks analysis, and nomogram construction were additionally performed. Higher MP grades correlated with worse OS and RFS (both P < 0.001), and MP > 40% was the strongest independent predictor of mortality (HR 8.60, 95% CI 4.58–16.13) and recurrence (HR 2.07, 95% CI 1.11–3.84). Sublobar resection independently predicted inferior OS (HR 2.45, 95% CI 1.59–3.78) and RFS (HR 2.40, 95% CI 1.60–3.59), persisting after PSM ( n = 390; both P < 0.001). A significant multiplicative interaction between MP burden and surgical approach was observed for OS (interaction HR 0.39, 95% CI 0.17–0.94, P = 0.035) but not RFS ( P = 0.716): the survival disadvantage of sublobar resection was greatest at low MP burden and attenuated at high MP burden. Competing risks analysis confirmed these associations for recurrence. MP grading and surgical extent are independent prognostic factors in resected lung adenocarcinoma, with MP > 40% representing the strongest adverse determinant. A significant interaction for OS indicated that the survival disadvantage of sublobar resection was most pronounced in patients with MP < 5% and was attenuated at MP > 20%; no such interaction was observed for RFS.