Elsevier

Journal of Bone Oncology

Volume 31, December 2021, 100399
Journal of Bone Oncology

Review Article
All bone metastases are not created equal: Revisiting treatment resistance in renal cell carcinoma

https://doi.org/10.1016/j.jbo.2021.100399Get rights and content
Under a Creative Commons license
open access

Highlights

  • Patients who develop RCC bone metastases continue to have a poor prognosis.

  • RCC bone metastasis treatment failure is more prevalent, likely in part because of longer patient survival.

  • RCC bone metastases frequently cause bone destruction that requires surgical intervention.

  • RCC bone metastases develop by a vicious cycle in bone that differs from breast cancer and prostate cancer, and more closely resembles multiple myeloma.

Abstract

Renal cell carcinoma (RCC) is the most common malignancy of the kidney, representing 80–90% of renal neoplasms, and is associated with a five-year overall survival rate of approximately 74%. The second most common site of metastasis is bone. As patients are living longer due to new RCC targeting agents and immunotherapy, RCC bone metastases (RCCBM) treatment failure is more prevalent. Bone metastasis formation in RCC is indicative of a more aggressive disease and worse prognosis. Osteolysis is a prominent feature and causes SRE, including pathologic fractures. Bone metastasis from other tumors such as lung, breast, and prostate cancer, are more effectively treated with bisphosphonates and denosumab, thereby decreasing the need for palliative surgical intervention. Resistance to these antiresportives in RCCBM reflects unique cellular and molecular mechanisms in the bone microenvironment that promote progression via inhibition of the anabolic reparative response. Identification of critical mechanisms underlying RCCBM induced anabolic impairment could provide needed insight into how to improve treatment outcomes for patients with RCCBM, with the goals of minimizing progression that necessitates palliative surgery and improving survival.

Keywords

Renal cell carcinoma
Bone
Metastasis
Bisphosphonate
Denosumab
Anabolic failure

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