An interdisciplinary consensus on the management of bone metastases from renal cell carcinoma

Abstract

Bone is a major site of haematogenous tumour cell spread in renal cell carcinoma (RCC), and most patients with RCC will develop painful and functionally disabling bone metastases at advanced disease stages. The prognosis of these patients is generally poor and the treatment is, therefore, aimed at palliation. However, RCC-associated bone metastases can be curable in select patients. Current data support a multimodal management strategy that includes wide resection of lesions, radiotherapy, systemic therapy, and other local treatment options, which can improve quality of life and survival. Nevertheless, the optimal approach for metastatic bone disease in RCC has not yet been defined and practical recommendations are rare. To improve the management and outcomes of patients with RCC and bone metastases, the International Kidney Cancer Coalition and the interdisciplinary working group on renal tumours of the German Cancer Society convened a meeting of experts with a global perspective to perform an unstructured review and elaborate on current treatment strategies on the basis of published data and expertise. The panel formulated recommendations for the diagnosis and treatment of patients with RCC and metastasis to the bone. Furthermore, the experts summarized current challenges and unmet patient needs that should be addressed in the future.

Fig. 1. Radiographic pattern of RCC bone metastases.

Bone metastases from renal cell carcinoma (RCC) can present in different patterns. a | Osteolytic bone metastases (arrowheads) that present with a symptomatic pathological fracture of the vertebral body (arrow) can be seen. b | Osteolytic bone metastases that present with an extraosseous soft-tissue portion in proximity to the sternoclavicular joint (dashed circle) can be seen. c | Bone metastases that result in bone formation (osteoblastic lesions) are rare (arrows).

Fig. 2. Radionuclide pattern of bone metastases from RCC.

Multiple osseous bone metastases (arrows) detected by technetium-99 m (^99mTc)-phosphonate bone scintigraphy in anterior (part a) and posterior (part b) views. Transversal CT (part c) depicts osteolysis of the posterior right acetabulum (arrow), which shows only partially activated bone metabolism (arrow) on single-photon emission CT (SPECT)–CT (part d). RCC, renal cell carcinoma.

Fig. 3. Imaging techniques for RCC bone metastases.

Bone metastases of the lumbar spine are detected by MRI or CT. T1-weighted sagittal (part a), T2-weighted sagittal (part b) and T2-weighted axial (part c) MRIs show the destruction of the fifth lumbar vertebra. MRI offers benefits for the assessment of the spinal canal and its possible involvement (arrow and dashed circle). By contrast, CT imaging (part d) has the advantage of displaying the structure of the mineral bone and enables assessment of its stability in the case of osteolysis (arrowhead). RCC, renal cell carcinoma.

Fig. 4. Proposed treatment algorithm for patients with RCC and bone metastasis.

The multidisciplinary expert panel proposes an algorithm for the management of patients with metastatic bone disease arising from renal cell carcinoma (RCC). The extent and location of metastasis should be assessed using CT and/or MRI. In patients with oligometastatic bone disease, disease cure is the aim of treatment and surgery is the preferred treatment option. However, other definitive therapy options might also be applicable, and the approach should be individualized to the needs of the patient. In other patients, management aims to palliate symptoms. In patients with multilocular bone metastases, treatment choice depends on the presence of symptoms. Asymptomatic patients can either undergo active surveillance or pre-emptive therapy in cases of high-risk disease. Symptomatic patients with multilocular disease should be assessed for local treatment first. Instability, fracture, pain, neurological impairment, and individual decision should be used for proper clinical judgement of local therapies. Surgery with or without radiotherapy remains the mainstay of treatment in symptomatic disease, but the approach should be individualized. Medical treatment can be given in the presence of residual disease or additional metastases but is not recommended as an adjunct after complete resection or definite locoregional treatment. In patients with multilocular bone and visceral metastases, systemic therapy is the mainstay of treatment, which can be amended by local treatments depending on pain, fracture, instability, or neurological symptoms. Bone-targeted agents can be used in patients with multilocular bone disease as an adjunct to locoregional or systemic therapies, which are the cornerstones to treat bone disease from RCC. An individual decision should be made for the duration of bone-targeted therapies, as specific adverse events of the bone can occur with long-term use. Stage of disease, individual risk of local complications, and patient symptoms should be used for clinical decision-making.