Survival outcomes and incidence of brain recurrence in high-grade neuroendocrine carcinomas of the lung: Implications for clinical practice

• Treatment of advanced LCNECs of the lung is not well established.
• Advanced LCNECs treated with platinum/etoposide ± thoracic RT bear a poor prognosis.
• Stage III and IV LCNECs have a rate of brain recurrence of 58% and 48% at 18 months.
• Whether PCI may reduce brain recurrence over time should be prospectively assessed.

BackgroundAmong patients with advanced high-grade neuroendocrine carcinoma (HGNEC) of the lung, the optimal therapeutic management is much less established for large cell neuroendocrine carcinomas (LCNECs) than for small cell lung cancers (SCLCs). We evaluated the survival outcomes and incidence of brain recurrence of advanced LCNECs, and compared them with those of a population of SCLCs matched by stage.Materials and methodsForty-eight unresected stage III HGNECs (16 LCNECs and 32 SCLCs) and 113 stage IV HGNECs (37 LCNECs and 76 SCLCs) were eligible for the analysis. The efficacy of platinum-etoposide chemotherapy with or without thoracic radiotherapy (TRT) and/or prophylactic cranial irradiation (PCI) was investigated.ResultsOverall response was significantly lower for LCNECs compared with SCLCs for both stage III (43.8% vs 90.6% respectively, P = 0.004) and stage IV (43.3% vs 64.5%, respectively, P = 0.04). Similarly, an inferior outcome was observed in terms of progression-free survival (PFS), and overall survival (OS) for LCNECs compared with SCLCs, which, however, reached significance only for stage III disease (median: 5.6 vs 8.9 months, P = 0.06 and 10.4 vs 17.6 months, P = 0.03 for PFS and OS, respectively). In the lack of PCI, LCNECs showed a high cumulative incidence of brain metastases, as 58% and 48% of still living stage III and IV patients, respectively, developed brain metastases at 18 months.ConclusionPatients with advanced LCNECs are at high risk for brain recurrence. Unresected stage III LCNECs treated with platinum-etoposide with or without TRT bear a dismal prognosis, when compared indirectly with SCLC counterparts. Randomized trials should evaluate whether PCI could improve survival of advanced LCNECs.