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Review
. 2021 Nov 28:31:100405.
doi: 10.1016/j.jbo.2021.100405. eCollection 2021 Dec.

Bone metastases from urothelial carcinoma. The dark side of the moon

Marco Stellato  1   2 , Daniele Santini  1   2 , Maria Concetta Cursano  1   2 , Simone Foderaro  1   2 , Giuseppe Tonini  1   2 , Giuseppe Procopio  3   2
Affiliations
Review

Bone metastases from urothelial carcinoma. The dark side of the moon

Marco Stellato et al. J Bone Oncol. .

Abstract

Bone metastases are common in genitourinary cancers, but they are underreported and not well researched. Synchronous bone metastases occur in 1.39-5.5% of bladder cancer patients, while 30-40% of cases are metachronous. Bone morphogenetic proteins (BMPs) play a key role in regulating proliferation, migration and invasion of tumor cells in bone microenvironment of bone metastases from metastatic urothelial carcinoma (mUC). Bone metastases represent a poor prognostic factor due to high morbidity and mortality correlated to skeletal-related events (SREs). The incidence rate of SREs in bladder, renal pelvis, and ureteral cancer varies from 39 to 68%. Radiotherapy is the most frequent treatment for SREs. The early use of bone targeted therapies (BTT), zoledronic acid and denosumab, improves SREs incidence and morbidity and it seems to improve overall survival (OS). To date, several new agents (immunotherapy and targeted drugs) demonstrated efficacy in mUC. However, subgroup analysis for bone metastases is often not available, due to difficulties in analysing bone samples, non-RECIST lesions and delay in systemic treatment due to SREs that limit the enrolment of bone mUC patients in clinical trials. Larger solid tumor studies that included UC patients are the main source of data for the management of mUC patients with bone metastases. For these patients, multidisciplinary approach should be preferred, involving orthopaedics, radiotherapists and rehabilitation to improve outcome and quality of life. New prospective trials should characterize clinical and molecular features of patients with bone metastases and the impact of new drugs on this poor prognostic metastatic site.

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Conflict of interest statement

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.

Figures

Fig. 1
Fig. 1
Bone morphogenetic proteins and bone metastases from urothelial carcinoma. BMP2: bone morphogenetic proteins 2; BMPR: bone morphogenetic proteins receptor; TNF alpha: tumor necrosis factor alpha; Smad: small mother against decapentaplegic; Med19: mediator complex subunit 19; P: phosphoryl group.
See this image and copyright information in PMC

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