Targeted Therapy of Bone Metastases in Renal Cell Carcinoma

he activity of targeted therapy on bone metastases from a single center were reported by Dr. Sczylick. He reported his experience with interferon, sorafenib, and sunitinib in the treatment of metastatic RCC with bone metastases.

Sunitinib was superior to the other drugs in delaying or preventing the progression of existing bone metastases as well as preventing the development of new bone metastases while on therapy.Surgical approaches to RCC bone metastases were discussed by Dr. Missenard and Dr. Casey. Surgery for bone metastases should primarily be reserved for those with a single isolated metastasis (which is extremely rare), and in patients with threatening metastases associated with significant symptoms or in patients with a threatening or existing pathologic fracture.Surgical approaches typically involve preoperative embolization, followed by surgical resection. Adjuvant XRT is sometimes used to decrease risk of recurrence but can impact wound healing. Median survival for patients is generally in the range of 1 year.The role of bisphosphonates in the management of RCC metastatic to bone was presented by Dr. Coleman. Thirty percent of patients with metastatic RCC will develop bone metastases. In the recently completed trial that compared zoledronic acid to placebo in decreasing the incidence of skeletal related events, there were 46 patients with metastatic RCC. Treatment with zoledronic acid decreased the risk of skeletal complications by 58% in the RCC population and significantly prolonged the time to first skeletal complication. Bisphosphonates can act at multiple points in the metastatic cascade and may have multiple mechanisms of action. They are thought to induce tumor cell apoptosis through the inhibition of angiogenesis. Treatment with zoledronic acid has been associated with a rare complication of osteonecrosis of the jaw, which is thought to occur at a rate of 1% per year on therapy. It was felt that the benefits of therapy far outweighed the minimal risks in the treatment of patients with metastatic RCC and bone metastases. RANK ligand inhibitors are on the near horizon as an improved therapy to prevent the morbidity of skeletal related complications.(Source: European International Kidney Cancer Symposium : University of Warsaw : May 2007.)