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      Skeletal metastasis in renal cell carcinoma: A review

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          Abstract

          Background

          Renal cell carcinoma account for 3% of all cancers, with peak incidence between 60 and 70 years of age predominantly affecting male population. Renal carcinoma is the most common malignancy of kidney constitutes for 80–90% of renal neoplasm with an overall 45% five years survival rate. Majority are diagnosed incidentally during investigation for other disease process of abdomen. Classical triad of gross hematuria, pain and palpable mass in abdomen is rare accounting to only 6–10%. Treatment of early stages of disease i.e. localized disease is partial or radical nephrectomy. Most common metastasis in RCC occurs to lung, followed by bone involvement in 20–35%, lymph nodes, liver, adrenal gland and brain. In metastatic disease median survival rate of patient is about eight months with 50% mortality rate within first year of life, five years survival rate is 10%. Skeletal metastasis are very destructive in patients with renal cell carcinoma compromising bone integrity leading to skeletal related events including pains, impending fractures, nerve compressions, hypercalcemia and even pathological fractures which may require surgical interventions and other therapy. In addition to skeletal complications, presence of bone metastases in RCC has negative impact on progression free survival and overall survival of patients treated with systemic therapies.

          Objective

          In this review we discuss pathophysiology of tumor metastasis, diagnosis, management and Case examples of metastatic renal cell carcinoma.

          Conclusion

          Incidence of metastatic renal carcinoma is increasing. Overall prognosis of patient with advanced RCC is poor, emphasizing the importance of early detection and prompt treatment of primary lesion in its early stage. Advancement in targeted therapy in recent decades had made some improvement in treatment of SREs and has helped in improving patent's quality of life but still we are in need of further improvement in treatment modalities to cure disease thereby decreasing morbidity and mortality.

          Highlights

          • Renal cell carcinoma account for 3% of all cancers.

          • It is a very destructive that may compromise bone integrity.

          • Most common metastasis in renal cell carcinoma occurs to lung, followed by bone , lymph nodes, liver, adrenal gland and brain.

          • Most common metastasis in renal cell carcinoma occurs to lung, followed by bone involvement in 20–35%, lymph nodes, liver, adrenal gland and brain.

          • In metastatic disease median survival rate of patient is about eight months with 50% mortality rate within first year of life, five years survival rate is 10.

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          Most cited references65

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          Revised RECIST guideline version 1.1: What oncologists want to know and what radiologists need to know.

          The objectives of this article are to review the new Response Evaluation Criteria in Solid Tumors (RECIST) guideline, version 1.1, highlighting the major changes in the new version compared with the original RECIST guideline (version 1.0), and to present case examples with representative imaging. Familiarity with the revised RECIST is essential in day-to-day oncologic imaging practice to provide up-to-date service to oncologists and their patients. Some of the changes in the revised RECIST affect how radiologists select, measure, and report target lesions.
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            Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates.

            Patients with bone metastases and elevated urinary N-telopeptide (uNTx), representing excessive bone resorption, are at increased risk for skeletal-related events (SREs), cancer progression, and death. Osteoclast-mediated bone resorption is regulated by RANKL. We evaluated the effect of denosumab, a fully human monoclonal antibody against RANKL, in patients with bone metastases and elevated uNTx levels despite ongoing intravenous (IV) bisphosphonate (BP) therapy. Eligible patients had histologically confirmed malignancy, > or = 1 bone metastases, and uNTx levels higher than 50 nmol/L bone collagen equivalents (BCE)/mM creatinine despite IV BPs. They were stratified by tumor type and screening uNTx levels (50 to 100 or > 100 nmol/L BCE/mM creatinine), and randomly assigned to continue IV BPs every 4 weeks or receive subcutaneous denosumab 180 mg every 4 weeks or every 12 weeks. Among 111 patients accrued, the primary end point of uNTx levels lower than 50 nmol/L BCE/mM creatinine (uNTx < 50) at week 13 was achieved by 49 (71%) of 69 patients in the denosumab arms, compared with 10 (29%) of 35 patients in the IV BP arm (P < .001). The proportion of patients with uNTx lower than 50 was maintained at week 25 (64% denosumab arms; 37% IV BP arm; P = .01). The incidence of SREs was six (8%) of 73 and six (17%) of 35 in the denosumab group and IV BP group, respectively. Rates of adverse events were similar between treatment groups. Among patients with elevated uNTx despite ongoing IV BP therapy, denosumab normalized uNTx levels more frequently than the continuation of IV BP. Fewer patients receiving denosumab experienced on-study SREs than those receiving IV BPs.
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              High-dose, single-fraction image-guided intensity-modulated radiotherapy for metastatic spinal lesions.

              To report tumor control and toxicity for patients treated with image-guided intensity-modulated radiotherapy (RT) for spinal metastases with high-dose single-fraction RT. A total of 103 consecutive spinal metastases in 93 patients without high-grade epidural spinal cord compression were treated with image-guided intensity-modulated RT to doses of 18-24 Gy (median, 24 Gy) in a single fraction between 2003 and 2006. The spinal cord dose was limited to a 14-Gy maximal dose. The patients were prospectively examined every 3-4 months with clinical assessment and cross-sectional imaging. The overall actuarial local control rate was 90% (local failure developed in 7 patients) at a median follow-up of 15 months (range, 2-45 months). The median time to local failure was 9 months (range, 2-15 months) from the time of treatment. Of the 93 patients, 37 died. The median overall survival was 15 months. In all cases, death was from progression of systemic disease and not local failure. The histologic type was not a statistically significant predictor of survival or local control. The radiation dose was a significant predictor of local control (p = 0.03). All patients without local failure also reported durable symptom palliation. Acute toxicity was mild (Grade 1-2). No case of radiculopathy or myelopathy has developed. High-dose, single-fraction image-guided intensity-modulated RT is a noninvasive intervention that appears to be safe and very effective palliation for patients with spinal metastases, with minimal negative effects on quality of life and a high probability of tumor control.
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                Author and article information

                Contributors
                Journal
                Ann Med Surg (Lond)
                Ann Med Surg (Lond)
                Annals of Medicine and Surgery
                Elsevier
                2049-0801
                31 January 2018
                March 2018
                31 January 2018
                : 27
                : 9-16
                Affiliations
                [1]Aga Khan University Hospital Karachi, Pakistan
                Author notes
                []Corresponding author. Yasir.mohib@ 123456aku.edu
                Article
                S2049-0801(18)30006-2
                10.1016/j.amsu.2018.01.002
                5832646
                29511536
                4fd3a284-524d-498c-8f10-419f71892adc
                © 2018 Published by Elsevier Ltd on behalf of IJS Publishing Group Ltd.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 9 October 2017
                : 14 January 2018
                Categories
                Review Article

                renal cell carcinoma,nephrectomy,pathological fracture,impending fracture,metastasis

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