Clinicopathological Characteristics of Extrapulmonary Neuroendocrine Carcinomas: Treatment Responses and Survival Outcomes: Single-Center Experience

<b>Background/Objectives</b>: Extrapulmonary neuroendocrine carcinomas (EP-NECs) are rare, aggressive malignancies with no standardized treatment approach. Although platinum-based chemotherapy is considered the first-line therapy, overall survival (OS) and progression-free survival (PFS) remain limited. This study aims to evaluate the clinical and pathological characteristics of EP-NEC patients, their treatment responses, and survival outcomes. <b>Methods</b>: This retrospective observational study included 29 EP-NEC patients diagnosed and followed between 2015 and 2024. Clinical and demographic data, tumor localization, disease stage, administered treatments, and survival outcomes were analyzed. Kaplan-Meier survival analysis was used to assess OS and PFS, with subgroup comparisons performed via the log-rank test. <b>Results</b>: The most common primary tumor sites were the pancreas (21%), prostate (17%), and cervix (14%). At diagnosis, 55.2% of patients had metastatic disease. First-line platinum-based chemotherapy achieved an objective response rate of 82.1%, with a median PFS of 8.16 months and a median OS of 14.16 months. Surgical intervention significantly improved survival (<i>p</i> = 0.020), while a high Ki-67 proliferation index (>80%) was associated with worse PFS (<i>p</i> = 0.032). Other factors, including smoking status and liver-directed therapies, had no significant impact on survival. <b>Conclusions</b>: EP-NECs present with a poor prognosis despite platinum-based chemotherapy achieving high response rates. Surgical resection improves survival outcomes, whereas high Ki-67 expression is associated with a worse prognosis. These findings highlight the need for further research into novel therapeutic strategies for EP-NECs.