Identification of Areas for Improvement in the Management of Bone Metastases in Patients with Neuroendocrine Neoplasms

Neuroendocrinology. 2020;110(7-8):688-696. doi: 10.1159/000504256. Epub 2019 Oct 22.

Abstract

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 lung NENs (April 2002 to March 2018) was conducted. Baseline characteristics, nature of BMs, treatment received and overall survival (OS) were evaluated. Statistical analyses were performed using SPSS version 23.0/STATA v12.

Results: Of 1,212 patients, 85 (7%) had BMs; median age 58 years. 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 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, 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.

Keywords: Bisphosphonates; Bone metastases; Hypercalcaemia; Palliative radiotherapy; Skeletal-related events; Survival.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Bone Neoplasms / diagnosis*
  • Bone Neoplasms / mortality
  • Bone Neoplasms / secondary
  • Bone Neoplasms / therapy*
  • Cohort Studies
  • Delivery of Health Care / standards
  • Delivery of Health Care / statistics & numerical data
  • Diphosphonates / therapeutic use
  • Female
  • Humans
  • Lung Neoplasms / diagnosis
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Lung Neoplasms / therapy
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasms, Unknown Primary / diagnosis
  • Neoplasms, Unknown Primary / mortality
  • Neoplasms, Unknown Primary / pathology
  • Neoplasms, Unknown Primary / therapy
  • Neuroendocrine Tumors / diagnosis*
  • Neuroendocrine Tumors / mortality
  • Neuroendocrine Tumors / pathology
  • Neuroendocrine Tumors / therapy*
  • Palliative Care / methods
  • Palliative Care / statistics & numerical data
  • Practice Patterns, Physicians' / standards
  • Practice Patterns, Physicians' / statistics & numerical data
  • Prognosis
  • Quality Improvement
  • Radiotherapy, Adjuvant / statistics & numerical data
  • Retrospective Studies
  • Survival Analysis
  • Treatment Outcome
  • United Kingdom / epidemiology

Substances

  • Diphosphonates