Treatment outcomes in patients with stage IV large cell neuroendocrine carcinoma: a nationwide registry study

Overall survival (OS) of patients with stage IV large cell neuroendocrine carcinoma (LCNEC) is poor and optimal systemic treatment is unknown. Here, we describe clinical outcomes per treatment strategy of patients with stage IV LCNEC, including stratification by immunohistochemical (IHC) protein RB1 (pRb) status.

Clinical data were obtained from all patients with LCNEC (2019-2022) in the Netherlands Cancer Registry (NCR). Central pathology review and IHC pRb staining were performed when tumor material was available. OS was calculated from time of diagnosis of stage IV until death, last OS update was April 2024.

In total 269/530 patients (51 %) received systemic treatment, and 132 samples were eligible for pathology review. In 88/132 (67 %) the diagnosis LCNEC was confirmed (other diagnoses: SCLC (34 %), NSCLC NOS (34 %)). The median OS of all panel-reviewed LCNEC patients was 7.4 months. Patients treated with chemo-immunotherapy had a numerically, but not statistically significant different survival compared to chemotherapy (median OS 9.6 months versus OS of 6.5 months; HR 0.71, 95 % CI 0.42-1.2). This was different from the real-world LCNEC patients, where a benefit of immunotherapy was observed (median OS 10.7 months versus OS of 6.7 months; HR 0.53, 95 % CI 0.4-0.72).

In real-world half of patients with stage IV LCNEC do not receive systemic treatment. Accurate diagnosing LCNEC is challenging and therefore introduces bias (i.e. other diagnoses as SCLC instead of LCNEC) in real-world cohorts, which in turn has impact on analysis of treatment outcomes. Patients with panel-reviewed LCNEC have a poor prognosis and no statistically significant improvement was observed with chemo-immunotherapy.