Extrapulmonary Small Cell Carcinoma: A Single Institution Review of Brain Metastases, Treatment Paradigms and Patient Outcomes

Extrapulmonary small cell carcinoma (EPSCC) is a rare entity with 1,000 cases reported annually in the U.S. It can originate in a variety of sites outside of the lung, and even with locoregional disease, relapse is common, and survival is poor. Prophylactic cranial irradiation (PCI) can improve survival in small cell lung carcinoma, however in the setting of EPSCC its role has not been clearly defined. We offer a single institution retrospective review of EPSCC, outlining the incidence of brain metastases, treatment paradigms, and patient outcomes.Patients with available records were identified from an institutional database. Demographic, disease-related, and treatment details were abstracted from the electronic medical record. Clinical outcomes were obtained by medical record review and brain metastases were identified through diagnostic imaging. Patients were classified as having brain metastases at diagnosis or in follow-up. Brain metastasis-free survival (BMFS) was defined as the duration of time from diagnosis to the development of brain metastases, and extracranial progression-free survival (ePFS), as the duration of time from diagnosis to progression of disease outside the brain. Time to event outcomes were summarized using the Kaplan-Meier method. Analyses were performed using R version 3.6.In total, 68 patients met eligibility criteria for analysis. The majority were male (66%) and median age was 68. The most common primary sites were genitourinary (32%) and gastrointestinal/hepatobiliary (22%). Thirty-eight patients (56%) had diagnostic brain imaging at time of diagnosis, with brain metastases present in 5 (13%). Treatment was delivered to 53 patients (80%) and treatment modalities included chemotherapy (n = 46), radiotherapy (n = 21), and surgery (n = 18). Median follow-up was 9.3 months for all patients and 10.3 months for surviving patients. Overall, 12 patients were observed to have brain metastases: 5 at diagnosis and 7 in follow-up. The competing risk of death without brain metastases at 1 year was 51.5%. Four of 5 patients with de novo brain metastases received WBRT. Of the 7 patients with subsequent brain metastases, 1 received salvage WBRT and 3 received salvage SRS. In total, 49 patients died and median OS was 10.0 months. Those with brain metastases had no significant difference in OS when compared to those without brain metastases (10.8 months v. 9.4 months). There was no association between primary type and survival.EPSCC is a rare entity that is most commonly diagnosed in the genitourinary system. In contrast to SCLC, the incidence of brain metastases is uncommon. No difference in survival was observed between patients with or without brain metastases. While retrospective studies must be interpreted with caution, our data suggest that the risks of PCI may outweigh the benefits. Further studies investigating the role of brain imaging surveillance, as well as the optimal management of brain metastases, is warranted.