Identification of areas for improvement in the management of bone metastases in patients with neuroendocrine neoplasms

Background: There is no global consensus on the optimal management of bone metastases (BMs) in neuroendocrine neoplasms (NENs). Objectives: To review current management and outcomes of patients with BMs in NENs, in order to identify areas for improvement. Methods: A retrospective study of all patients with NENs, except Grade 3 (G3) lung NENs (April 2002-March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS v23.0/STATA v12. Results: Of 1212 patients, 85 (7%) had BMs; median age 58 years. The majority had a gastro-enteropancreatic primary (49%, n=42) followed by lung (25%, n=21), unknown primary (20%, n=17), and “others” (6%, n=5). Two-thirds (n=57) had G1-2 neuroendocrine tumours, and 41% (n=35) had functional tumours. Overall, 28% (n=24) presented with synchronous BMs at first NEN diagnosis, and 55% (n=47) developed BMs at the same time as other distant metastases. For the subpopulation of patients in whom BMs developed metachronously to other distant metastases (45%, n=38), median time to development of BMs was 14.0 months. BMs were ‘widespread’ in 61% (n=52). Although only 22% (n=19) reported symptoms at initial diagnosis of BMs, most (78%) developed symptoms at some time during the follow-up period (pain/hypercalcaemia 64%, skeletal-related events 20%). BMs were mainly managed with analgesia (44%, n=37). Radiotherapy and bisphosphonates were used in 34% (n=29) and 22% (n=19), respectively. Surgery was rarely performed (2%, n=2). Median OS from identification of BMs was 31.0 months, and 18.9 months from development of BMs-related symptoms. Conclusions: In this cohort study, most patients with BMs developed symptoms. The utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patients’ quality of life and survival outcomes.