In the four countries considered, more than 83 % of costs were due to inpatient stay for spinal cord compression and bone surgery. For non-vertebral fractures in the UK and Spain, more than 88 % of costs were due to inpatient stays, while in Italy and Germany, this proportion was 79 % (19 % for procedures) and 64 % (28 % for procedures), respectively. For vertebral fractures in Italy and Spain, more than 94 % of costs were due to inpatient stays, while in Germany this category of cost covered 83 % of costs (14 % due to procedures) and in the UK 9 % were due to inpatient stays, 37 % to outpatient visits, and 53 % to procedures. The wider difference in terms of costs’ proportion among countries was observed also for radiation therapy: in Germany procedures covered 45 % of costs, followed by inpatient stays (42 %) and outpatient visits (13 %); in Italy 78 % of costs were due to procedures, followed by inpatient stays (17 %); in Spain the main cost category was inpatient stays (64 %) followed by outpatient visits (27 %) and procedures (9 %); and in the UK 50 % of costs were due to outpatient visits and 47 % to procedures.

The highest cost was associated with surgery to bone followed by spinal cord compression in Germany, with spinal cord compression followed by surgery to bone in Italy and the UK, and with spinal cord compression followed by vertebral fracture in Spain, confirming the high regional variability of procedures and cost.

Previous analysis, indeed, had been conducted on the population of single countries. In 2011, Félix et al. [14] conducted a multicenter, retrospective study to assess skeletal-related events’ costs in 152 patients with bone metastases in prostate (31 patients) and breast (121 patients) cancers in Portugal. Cost data were estimated according to the Portuguese National Health Service price list, considering activities provided by the hospitals involved in SRE identification and treatment. The estimated mean per capita costs related to skeletal events were 5,711 € (95 CI: 3,467 €–6,052 €) for patients with prostate cancer. In the prostate cancer group, the three main cost categories were hospitalization (38.7 %), medications (31.0 %), and radiotherapy (24.5 %). The mean cost per skeletal-related event in the whole sample is reported in the table below: the highest cost was associated with spinal cord compression, followed by pathologic fracture, hypercalcemia of malignancy, and radiotherapy.

The year before, Pockett et al. [15] had published a similar article aimed at investigating the hospital burden of SREs associated with bone metastases in prostate cancer, breast cancer, and lung cancer in the Spanish population. Data related to 221 patients with prostate cancer, bone metastases, and SREs with hospital admissions between 2000 and 2006 were considered. The average cost for the first hospital admission of patients with skeletal-related events was 3,585 € (standard deviation: ± 1,538.8 €), while the cost of the first hospital admission of patients with prostate cancer metastatic bone disease but no SREs was equal to 3,180 € (standard deviation: ±2,081.9 €). The impact of SREs on total costs had been demonstrated since 2003 also in the Netherlands, where Groot et al. [16] evaluated the direct medical costs associated with bone metastases in 28 patients with prostate cancer and found a cost per patient equal to 13,051 €, of which 6,983 € were directly due to SREs (more than half of total direct medical costs).

An effort to overcome regional differences and to conduct a wider European analysis on the costs of bone metastases and SREs has been recently made by Pereira et al. [17], with a retrospective multinational study (Austria, the Czech Republic, Finland, Greece, Portugal, Sweden) that investigated the health resource utilization associated with skeletal-related events in patients with bone metastases secondary to prostate, breast, or lung cancer and multiple myeloma. The data sources were hospital charts of 356 patients with >19 years who experienced 744 skeletal-related events. The cost per event (in euros, referred to 2010), calculated assuming the National Health Service perspective, is reported in the table below.

The mean cost per event among the six countries considered was 7,043 € for radiation to bone, 5,242 € for pathologic fracture, 11,101 € for surgery to bone, and 11,509 € for spinal cord compression. This last event was the most onerous in Austria, the Czech Republic, Finland, and Sweden, followed by surgery to bone. In Greece radiation to bone resulted to be the event with more health resource consumption, followed by surgery to bone, while in Portugal surgery to bone was the most expensive procedure, followed by treatment of spinal cord compression.