Prognostic Impact of Clinicopathological and Inflammatory Markers in Surgically Treated Pulmonary Invasive Mucinous Adenocarcinoma.

Abstract

Objective: Invasive mucinous lung adenocarcinoma (IMA) is a rare histological subtype representing 2-10% of lung adenocarcinomas and exhibits unique molecular and clinicopathological features. Due to its rarity and the limited number of published studies, prospective studies are not possible. Therefore, prognostic markers in patients with IMA who underwent surgery are still unclear.

Methodology: Data from patients with histopathologically confirmed pure IMA who underwent surgery between May 2020 and December 2024 were retrospectively analyzed. Demographic data, tumor size, localization, lymph node status, visceral pleural invasion [VPI], airspace spread [STAS], adjuvant therapy, and hematological indices thought to be prognostic in other cancer types were calculated. Estimated DFS and OS were calculated by the Kaplan-Meier method, and prognostic factors were investigated by Cox regression analysis.

Results: A total of 53 patients with surgically resected mucinous adenocarcinoma were included in the study. The median age was 66 years (range: 36-88). Of the patients, 54.7% were male (n = 29) and 45.3% were female (n = 24). Nineteen patients (35.8%) received adjuvant chemotherapy, and 7 patients (13.2%) received adjuvant radiotherapy. Postoperative pathological examination revealed that 24 patients (45.3%) had tumors ≥4 cm in diameter, 6 patients (11.3%) had lymph node metastasis, and 10 patients (18.9%) were STAS-positive. The estimated median disease-free survival (mDFS) for the overall population was 98.9 months. In patients with lymph node metastasis, mDFS was 4.5 months, while the median was not reached in patients without nodal involvement (log-rank, p < 0.001). In the presence of pleural invasion, mDFS was 42.7 months, while it was not reached in patients without invasion (log-rank, p = 0.008). In STAS-positive patients, mDFS was 18.6 months, compared to not reached in STAS-negative patients (log-rank, p = 0.039). For tumors ≥4 cm, mDFS was 47.1 months, while it was not reached for tumors <4 cm (log-rank, p = 0.021). Patients with right lung tumors had an mDFS of 52.8 months, whereas those with left lung tumors had a non-reached median (log-rank, p = 0.023). No significant differences in DFS were observed by age, sex, adjuvant chemotherapy, adjuvant radiotherapy, LVI, PNI and hematological indexes. The estimated median overall survival (mOS) for the entire cohort was 150.5 months. Patients with lymph node metastasis had a median OS of 10.2 months, while it was 150.5 months in patients without nodal involvement (p < 0.001). In the presence of pleural invasion, the mOS was 76.5 months, compared to 150.5 months in its absence (p = 0.008). STAS-positive patients had a mOS of 24.6 months, whereas STAS-negative patients had a mOS of 150.5 months (p = 0.001). No statistically significant differences in OS were observed according to age, sex, adjuvant chemotherapy, adjuvant radiotherapy, tumor size, LVI, PNI and hematological indexes. In univariable Cox regression analysis, tumor size ≥4 cm, lymph node metastasis (p < 0.001), pleural invasion (p = 0.012), STAS positivity (p = 0.047), and right-sided tumor location (p = 0.029) were identified as significant prognostic factors for DFS. Other variables were not associated with DFS. For OS, lymph node metastasis (p < 0.001), pleural invasion (p = 0.013), and STAS positivity (p = 0.002) were also found to be significant prognostic factors.

Conclusion: In conclusion, It was demonstrated that while lymph node metastasis, visceral pleural invasion and STAS presence were identified as poor prognostic indicators in patients with IMA, inflammatory markers did not predict prognosis.