Clinical presentation of bone metastases in neuroendocrine tumors: a retrospective cohort study

Bone metastases (BMs) are a rare and late event in patients with neuroendocrine tumors (NETs). The aim of our study was to investigate the clinical presentation and outcome of BMs in a large cohort of patients with NETs. A retrospective study was performed at two referral centers of Northern Italy (IRCCS Humanitas Research Hospital in Milan and Santa Maria della Misericordia University Hospital in Udine). Three hundred fifty-two consecutive patients with either gastroenteropancreatic or non-gastroenteropancreatic NETs were included: 52 patients with synchronous or metachronous BMs (BM-positive) and 300 patients with metastatic disease without BMs (BM-negative). Patients with BMs showed a higher prevalence of smoking habit (41.2 vs 21.8%, P = 0.004) and carcinoid syndrome (28.8 vs 5.7%, P <0.001) compared to patients without BMs. In addition, higher levels of chromogranin A (P = 0.001), urinary 5-hydroxyindoleacetic acid (P <0.001), parathyroid hormone (P = 0.022), and alkaline phosphatase (P = 0.018) were found compared to the BM-negative group. Patients with BMs had more frequently a primary lung NET compared to the BM-negative group (19.2 vs 0.7%, P = 0.001) and grade G2 or G3 gastroenteropancreatic tumors (P <0.001) compared to the BM-negative group. During a median follow-up of 4.2 years, a higher mortality rate was registered in the BM-positive group as compared to BM-negative group (42.3 vs 4.0%, P = 0.001). BMs were more common in patients with lung NETs, G2-G3 grade tumors, and in those with carcinoid syndrome. BMs affected patients' prognosis, highlighting the importance of investigating and managing this condition in patients with NETs.