Pulmonary atypical carcinoid (AC) demonstrates a variable prognosis influenced by both tumor biology and anatomic staging. It remains unclear whether histopathologic markers such as mitotic count, necrosis, and Ki-67 more effectively predict overall survival (OS) than nodal involvement (pN). This study aims to determine whether OS after surgical resection of pulmonary AC is more strongly associated with pathologic markers or with nodal involvement, by directly comparing their prognostic performance within a single institutional cohort. We retrospectively analyzed 111 patients with resected AC and complete OS data, comparing prognostic performance between a biologic model (mitoses > 2 per 2 mm2, necrosis present, Ki-67 > 10%), an anatomic model (pN > 0), and a combined model. Survival curves were estimated by Kaplan-Meier analysis. Model discrimination was evaluated using Harrell's C-index; nested models were compared via likelihood-ratio testing. Restricted mean survival time (RMST) at 60 months was used to quantify absolute survival differences by category. Median follow-up was 88 months (IQR 46-136 months). Proportions of high-risk features were: mitoses > 2 mm2, 66%; necrosis, 31%; Ki-67 > 10%, 42%; nodal involvement, 36%. The biologic model achieved a higher C-index (0.748) than the anatomic model (0.559), and the combined model showed minimal incremental gain (C-index = 0.755, p = 0.97 vs. biologic model). Only 11 deaths occurred during follow-up, which limits the precision of effect estimates. RMST analysis showed that the presence of necrosis was associated with the largest absolute difference in 60-month survival, followed by high mitotic count, elevated Ki-67, and nodal involvement. Histopathologic indicators of tumor biology, particularly necrosis and mitotic activity, were more strongly associated with OS than nodal stage. These findings support the potential value of pathology-anchored prognostic stratification in AC. Validation in larger multicenter cohorts is required before implications for clinical decision-making can be fully defined. These results may help refine postoperative counselling and surveillance strategies if prospectively confirmed.
Bertolaccini et al. (2026) studied this question.