Identification of the lymph node metastasis atlas and optimal lymph node dissection strategy in patients with resectable lung invasive mucinous adenocarcinoma: a real-world multicenter study.

Background: Lung invasive mucinous adenocarcinoma (LIMA) is a rare, unique, and heterogeneous subtype of lung cancer whose patterns of lymph node (LN) metastasis are unknown, and a consensus on LN dissection (LND) has not been reached. This study aimed to evaluate LN metastasis patterns in LIMAs and establish optimal LND strategies.

Methods: Data about 19,596 LNs from 1474 LIMA patients collected between January 2010 and December 2021 at 8 lung cancer research centers and tertiary hospitals across China, and data from 5304 LIMA patients between 2004 and 2021 in the SEER database were analysed. Metastasis probabilities were calculated for each LN station to construct a metastasis atlas. Statistical methods, including LOWESS fitting, restricted cubic spline, Kaplan-Meier, and logistic regression analyses, were employed to identify optimal LND strategies.

Results: Compared with non-mucinous adenocarcinoma patients, LIMA patients exhibited distinct clinicopathological features and a significantly lower probability of LN metastasis (4.20% vs. 7.19%, P < 0.05). Metastasis was most common in the peripheral and hilar/interlobar zones (especially stations 14 and 10), with minimal involvement in the lower zone (stations 8 and 9). A U-shaped relationship between the LN count and prognosis (including overall survival, relapse-free survival, and cancer-specific survival) was found, with 6-20 and 18 LNs as the optimal range and cut-off point, respectively. Excessive or insufficient dissection was linked to poorer outcomes. A predictive model (area under the receiver operating characteristic cure = 0.8367) revealed that patients with a probability ≥ 0.5 had a significantly greater proportion of patients with stage N1+ disease (including N1 and N2 patients) (68.09% vs. 11.63%, P < 0.001) and worse overall survival [hazard ratio (HR) = 4.00, 95% CI 2.72-5.87, P < 0.001] and relapse-free survival (HR = 5.53, 95% CI 3.97-7.71, P < 0.001). The minimum numbers of LNs for the low- (probability < 0.1), medium- (probability 0.1-0.5), and high- (probability > 0.5) risk patients were 7, 14, and 17, respectively. For those with uncertain metastatic risk, dissecting 18 LNs may be the most appropriate and robust strategy.

Conclusions: This study systematically revealed the pattern of LIMA-specific LN metastasis and proposed a risk-stratified LND strategy. These recommendations balance the imperatives of accurate staging with the preservation of long-term patient prognosis, offering a practical guideline for surgical decision-making.