Bone metastases (BMs) in patients with neuroendocrine neoplasms (NENs): Prevalence and clinical management in a tertiary cancer centre

Background: Bone metastases (BMs) are rare in neuroendocrine neoplasms (NENs). There is no global consensus on the optimal management, and treatment is often extrapolated from experience in other tumour groups. The aim of this study was to review the current management and outcomes of patients with BMs in NENs.

Method: A retrospective study was performed of all patients with NENs, except G3 lung NENs, treated at a tertiary centre from April 2002–March 2018. Baseline characteristics, nature of BMs, treatment received and overall survival were evaluated. Statistical analyses were performed using SPSSv23.0/STATAv12.

Results: A total of 1459 patients were screened; of these 85 (7%) had BMs; median age 58 years (IQR 47.5–67.5). The majority had a gastro-entero-pancreatic 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 disease. Twenty-four patients (28%) presented with de novo BMs at first NEN diagnosis, and 47 patients (55%) developed BMs synchronously with other distant metastases. In the remaining 38 patients (45%) in whom BMs were ‘late events’, median time to development of BMs was 14.0 months (95%-CI 3.1–24.9). BMs were ‘widespread’ in 61% (n=52). Although only 35% (n=30) reported symptoms at initial diagnosis of BMs, the majority (78%) later developed symptoms (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). The main reason for not requiring radiotherapy and/or bisphosphonates was that pain was adequately controlled with analgesia and/or systemic treatment. After a median follow-up of 30.9 months and 68% deaths, median overall survival from identification of BMs was 31.0 months (95%-CI 19.6–42.4) and 18.9 months (95%-CI 8.7–29.1) from time of development of BMs-related symptoms.

Conclusion: Most patients with BMs will develop symptoms. Although the majority appear to be adequately managed with analgesia, the utility of radiotherapy and/or bisphosphonates should be prospectively and systematically explored further for its potential impact on patient outcomes (both in terms of survival and quality of life).