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Background: In breast cancer and prostate cancer patients, bone metastases (BM) present the main cause of morbidity and often cause debilitating pain, impaired functioning and subsequent deterioration of quality of life (QoL). The management of BM is still challenging. Maintenance or improvement in QoL is the main goal of treatment. Antiresorptive treatment, such as denosumab and bisphosphonates, can help to reduce the frequency of skeletal complications, to control bone pain and potentially to improve QoL. The optimal time point for initiation of antiresorptive therapy is still discussed controversially. In patients with BM, bone pain can be used as a surrogate measure of QoL. However, limited data exist on health-related QoL in patients with BM under antiresorptive treatment. The PROBone registry study evaluated complaints and limitations caused by BM of breast and prostate cancer patients using patient-reported outcomes (PROs) in real-world in Germany., Methods: Between 2014 and 2019, 500 patients with histological confirmation of advanced breast or prostate cancer, diagnosed with BM at start of their first antiresorptive therapy were prospectively enrolled in 65 outpatient-centers specialized in medical oncology across Germany. Changes of QoL were assessed monthly from baseline until a maximum of 12 months using the validated pain score Functional Assessment of Cancer Therapy Quality of Life Measurement in patients with bone pain (FACT-BP) supplemented by questions on general pain and on the impact of time spent for treatment of illness on patients' daily activities. Statistical analysis was performed descriptively by relative and absolute frequencies., Results: In total, 486 patients were eligible for final analysis, of these 310 were diagnosed with breast cancer and 176 with prostate cancer. Median age was 67 years for breast cancer and 76 years for prostate cancer patients. 79.7% of breast cancer and 59.7% of prostate patients started antiresorptive treatment within 3 months after diagnosis of BM. More than 75% of patients suffered from bone pain at study inclusion. In total 52% of breast cancer patients and 47.9% of prostate cancer patients reported to take pain medication during the observation period. In breast and prostate cancer patients an initial pain reduction after start of BTA was observed: General pain and bone pain levels as well as the median FACT-BP score showed a constant improvement over the first months and maintained stable at a constant level afterwards. Subgroup analysis showed that patients without pain at baseline reported distinctly better FACT-BP scores throughout the whole observation period than patients with pain at baseline. Looking at time-stress (M)-scores, younger breast cancer patients (<65 years) showed highest burden especially during the first months of treatment., Conclusions: Our results indicate overall good adherence to current guideline recommendation, with most breast and prostate cancer patients starting antiresorptive therapy within the first 3 months after diagnosis of BM. This point gains even more importance as our data support current recommendations by ESMO guidelines as well as by German evidence-based S3-guidelines for diagnosis and treatment of breast and prostate cancer to initiate bone-targeted agents (BTA) as soon as BM are diagnosed, to keep pain levels at the lowest level possible, to minimize the debilitating effects of metastatic bone pain and maintain a good QoL. Bone pain management by an early use of BTA following BM diagnosis might improve patient care., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 iOMEDICO AG.)

Bone metastases (BM) are a common complication of cancer, whose management often requires a multidisciplinary approach. Despite the recent therapeutic advances, patients with BM may still experience skeletal-related events and symptomatic skeletal events, with detrimental impact on quality of life and survival. A deeper knowledge of the mechanisms underlying the onset of lytic and sclerotic BM has been acquired in the last decades, leading to the development of bone-targeting agents (BTA), mainly represented by anti-resorptive drugs and bone-seeking radiopharmaceuticals. Recent pre-clinical and clinical studies have showed promising effects of novel agents, whose safety and efficacy need to be confirmed by prospective clinical trials. Among BTA, adjuvant bisphosphonates have also been shown to reduce the risk of BM in selected breast cancer patients, but failed to reduce the incidence of BM from lung and prostate cancer. Moreover, adjuvant denosumab did not improve BM free survival in patients with breast cancer, suggesting the need for further investigation to clarify BTA role in early-stage malignancies. The aim of this review is to describe BM pathogenesis and current treatment options in different clinical settings, as well as to explore the mechanism of action of novel potential therapeutic agents for which further investigation is needed.

Bone represents a common site of metastasis from several solid tumours, including breast, prostate and lung malignancies. The onset of bone metastases (BM) is associated not only with serious skeletal complications, but also shortened overall survival, owing to the lack of curative treatment options for late-stage cancer. Despite the diagnostic advances, BM detection often occurs in the symptomatic stage, underlining the need for novel strategies aimed at the early identification of high-risk patients. To this purpose, both bone turnover and tumour-derived markers are being investigated for their potential diagnostic, prognostic and predictive roles. In this review, we summarize the pathogenesis of BM in breast, prostate and lung tumours, while exploring the current research focused on the identification and clinical validation of BM biomarkers.