Outcomes of Patients with Clinical Stage I-IIIA Large-Cell Neuroendocrine Lung Cancer Treated with Resection

Abstract

Large-cell neuroendocrine carcinoma (LCNEC) is a rare malignancy with poor prognosis. The rationale of the study was to determine the survival of LCNEC patients in I–IIIA clinical stages who underwent resection. A total of 53 LCNEC (89%) and combined LCNEC (11%) patients in stages I–IIIA who underwent surgery with radical intent between 2002–2018 were included in the current study. Overall survival (OS) and time to recurrence (TTR) were estimated. Uni- and multivariable analyses were conducted using Cox-regression model. Patients were treated with surgery alone (51%), surgery with radiochemotherapy (4%), with radiotherapy (2%), with adjuvant chemotherapy (41%), or with neoadjuvant chemotherapy (2%). The median (95% Confidence Interval (CI)) OS and TTR was 52 months (20.1–102.1 months) and 20 months (7.0–75.6 months), respectively. Patients treated in clinical stage I showed better OS than patients in stages II–IIIA (p = 0.008). Patients with R0 resection margin (negative margin, no tumor at the margin) and without lymph node metastasis had significantly better TTR. In the multivariate analysis, age was an independent factor influencing OS. Recurrence within 1 year was noted in more than half cases of LCNEC. R0 resection margin and N0 status (no lymph node metastasis) were factors improving TTR. Age >64 years was observed as a main independent factor influencing OS.

Large Cell Neuro-Endocrine Carcinoma of the Lung: Current Treatment Options and Potential Future Opportunities

“…Another large retrospective study from Gu et al showed that surgery, when feasible, significantly and independently improved OS compared to a cohort of not surgically treated patients (adjusted with propensity score matching-PSMmethod); this was demonstrated for stages I-II (p = 0.000), for stage IIIA (p = 0.001), and even for stage IIIB (p = 0.017), although the high recurrence rate after surgery alone justifies the need for a multimodal treatment in all-stage LCNEC (55). Several smaller series are in line with the above-mentioned studies, as demonstrated by Girelli et al ( 56), Lowczak et al (57), and Zacharias et al (58). The latter study also demonstrated a possible role for systematic mediastinal nodal dissection in improving outcomes in LCNEC, but this finding might be explained by a more accurate staging of the disease.…”

Recurrence-Free Survival in Early and Locally Advanced Large Cell Neuroendocrine Carcinoma of the Lung after Complete Tumor Resection

“…However, a clear prognostic value for the type of surgery in early-stage LCNEC has not been elucidated. Some evidence supports that a less radical surgery significantly increased the clinical outcome [ 7 , 34 ]. On the contrary, other works report better outcomes for patients who received lobectomy compared to the ones that received sub-lobar resections [ 14 ].…”

“…Interestingly, we identified a relevant role for patient age, with older patients having a significantly higher risk of tumor recurrence and death. A previous analysis detected age (≤64 vs. >64 years) as an independent factor influencing OS for LCNEC patients, with an increased risk of death in older patients, twice as higher compared to younger patients [ 34 ]. Recently, a nomogram model has been developed to predict the survival probability of LCNEC patients [ 35 ].…”

Risk factors, survival analysis, and nomograms for distant metastasis in patients with primary pulmonary large cell neuroendocrine carcinoma: A population-based study

“…( 10 ) However, LCNEC had a high postoperative recurrence rate, with more than half relapsing within one year, although the R0 resection margin and N0 status (no lymph node metastasis) improved the time to recurrence. ( 33 ) As a result, even for LCNEC patients with an earlier stage, surgery alone was insufficient. ( 34 ) Second, chemotherapy alone could be more beneficial than other treatments, even for patients in stage IV.…”