Outcomes for Surgery in Large Cell Lung Neuroendocrine Cancer

Abstract

Introduction: There are limited small, single-institution observational studies examining the role of surgery in large cell neuroendocrine cancer (LCNEC). We investigated the outcomes of surgery for stage I to IIIA LCNEC by using the National Cancer Database. Methods: Patients with stage I to IIIA LCNEC were identified in the National Cancer Database (2004-2015) and grouped by treatment: definitive chemoradiation versus surgery. Overall survival, by stage, was the primary outcome. Outcomes of surgical patients were also compared with those of patients with SCLC or other non-small cell histotypes. Results: A total of 6092 patients met the criteria: 96%, 94%, 75%, and 62% of patients received an operation for stage I, II, IIIA, and cN2 disease, respectively. Complete resection was achieved in at least 85% of patients. The 5year survival rates for patients undergoing an operation for stage I and II LCNEC were 50% and 45%, respectively. Surgical patients with stage IIIA and N2 disease had 36% and 32% 5-year survival rates, respectively. When compared with stereotactic body radiation in stage I disease and chemoradiation in patients with stage II to IIIA disease, surgery was associated with a survival benefit. Patients with LCNEC who underwent an operation generally experienced worse survival by stage than did those with adenocarcinoma but experienced improved survival compared with patients with SCLC. Perioperative chemotherapy was associated with improved survival for pathologic stage II to IIIA disease. Conclusions: Surgery is associated with reasonable outcomes for stage I to IIA LCNEC, although survival is generally worse than for adenocarcinoma. Surgery should be offered to medically fit patients with both early and locally advanced LCNEC, with guideline-concordant induction or adjuvant therapy.

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

“…The predominance of men was also reported in other studies and R0 resection was observed in 90-99.2% [2,20,28]. Other authors have also confirmed that the most frequently used surgery option was also lobectomy [5,25,26]. All analyzed patients, whose smoking status was known, were smokers.…”

“…Similar results (64.5%) were achieved in a single-institution retrospective analysis conducted on 125 patients [36]. In USA Raman et al [26] performed 5-year survival (50%, 45%, and 36% for CS I, II, and IIIA, respectively) using a largest cohort on the world (>6000 patients). Similar to Eichhorn et al [30], who determined that advanced nodal status was significantly associated with poor outcome, in our analysis, LCNEC patients treated with resection who did not show lymph node metastasis had better prognosis (OS and TTR) in comparison with N+ patients, although the difference was not statistically significant.…”

“…The authors determined that high-grade LCNEC patients had a better overall survival and cancer-specific survival than high-grade SCLC patients also in the regional stage, distant stage, and surgery subgroups. Raman et al [26] also confirmed better survival prognosis by stage I-IIIA of patients with LCNEC compared to SCLC. Chemotherapy treatment for LCNEC is a subject of debate since it seems to be less chemosensitive than SCLC.…”

“…These studies are rather primarily single-institution analyses limited by small cohort sizes and outdated results [3,5,18,25]. In a recent study Raman et al [26] performed a retrospective large cohort study including 6092 LCNEC patients with stages I-IIIA using the National Cancer Database to examine the outcomes of surgery by stage. In comparison to the United States, where data about 80% of cancers diagnosed across 1500 centers have been prospectively collected by independent tumor registrars [27], in Poland, the National Cancer Register have unfortunately not collected any data (such as stage of disease) to estimate the survival analyses.…”

“…The authors also noted that patients who underwent platinum-based adjuvant chemotherapy had a significantly lower rate of tumor recurrence and a higher rate of disease-free survival than those who had non-platinum-based adjuvant chemotherapy or no adjuvant chemotherapy. Raman et al [26] showed that perioperative chemotherapy was associated with improved survival for pathologic stage II-IIIA disease. In our multivariate analysis, next to age >64 years (p = 0.04), surgery alone (p = 0.02) was found to be associated with an increased risk of death.…”