Bone metastases from neuroendocrine neoplasms: Results of an Italian nationwide survey of natural history and management

Bone metastases (BMs) were reported in <15% of cases of neuroendocrine neoplasms (NENs). Their clinical behavior is various and clinical management is still undefined. This study aimed to describe the clinical practical management and survival outcome of neuroendocrine neoplasm patients with BMs. This is a retrospective, observational, multicenter, nationwide study, in which clinical-pathological characteristics, diagnostic tools, skeletal-related events (SREs), bone targeted agents (BTAs) and their correlation with clinical outcome were collected. Data from 320 patients from 18 Italian centers diagnosed with bone metastases during 2000–2013 were captured. Most patients had a well/moderately differentiated NEN, with synchronous distant metastases, mostly hepatic, the majority of which originated from a gastroenteropancreatic primary site. Bone was the first metastatic site in 41% of patients. After a median follow-up of 27 months 122 patients died. The median overall survival (OS) was 62 months. In 22% of patients (n = 72), SREs were observed, and 31% of patients received a BTA. At multivariable analysis of factors associated with OS after the development of BMs, primary lung site, Ki-67 ≥55% versus ≤20%, >10 BMs, mixed pattern (osteoblastic/osteolytic) versus osteoblastic, prior lung metastases and SREs were found to be significant poor prognosis factors. At multivariable analysis Ki-67 ≥55% versus ≤20% remains significantly associated with the development of SREs. Our study represents a real-life nationwide scenario of a large series of NEN patients with BMs handled at dedicated centers. Several hypotheses generated by this study are warranted to be tested in future homogeneous studies, including objective criteria for the use of BTAs.