Background and Objectives: Pulmonary large-cell neuroendocrine carcinoma (pLCNEC) is a rare malignancy, accounting for approximately 2–3.5% of surgically resected primary lung cancers. Given its rarity, pLCNEC has been less extensively studied than other, more common lung cancer subtypes. In this study, we evaluated and compared the diagnostic and therapeutic approaches to pLCNEC. Materials and Methods: Patients with pLCNEC were evaluated with respect to age, sex, smoking history, primary tumor site, surgical history, tumor stage, histological subtype, metastatic sites at initial diagnosis and during follow-up, first- and second-line chemotherapy regimens, and disease survival parameters. Results: A total of 55 patients diagnosed between 2012 and 2024 were retrospectively analyzed. The median age at diagnosis was 63 years, the mean smoking exposure was 45.8 pack-years, and the median overall survival (mOS) for the entire cohort was 9 months (95% CI, 7–11). At presentation, 12.7% of the patients had stage I–II, 29.1% had stage III, and 58.2% had stage IV disease. Primary tumors were located peripherally in 85.5% of cases and centrally in 14.5%. A platinum plus etoposide regimen—standard for small-cell lung cancer (SCLC)—was the most commonly administered first-line chemotherapy (n = 40). Among all patients, 19 had undergone upfront surgical resection, whereas 36 had not. In univariate analysis, patients with a history of surgery (n = 19) had a significantly longer mOS than those without surgery (n = 36): 16 months (95% CI, 8–NR) versus 7 months (95% CI, 3–9), respectively (p = 0.003). On multivariate analysis, stage IV disease, ECOG PS ≥ 2, and advanced age were independently associated with poorer survival. In multivariable analyses, surgery showed a borderline association with survival that did not reach statistical significance (p = 0.052). Furthermore, median survival was significantly longer in patients with T1 stage disease compared with those with T3 and T4 stage, and in those with T3 compared with T4 stage (p = 0.045). Conclusion: Overall, early-stage diagnosis and surgical intervention may be associated with favorable clinical outcomes and a survival benefit.
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Bölükbaşı et al. (2026) studied this question.
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