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• W2137128518 abstract "Kidney cancer is estimated to affect more than 54,000 individuals in the United States each year and to be responsible for 13,000 deaths in the United States annually. When a patient with localized kidney cancer is treated surgically, 5and 10-year disease-specific survival can approach 95%. However, despite the remarkable recent advances in targeted therapeutics for kidney cancer, this disease is still fatal for the majority of patients who present with advanced disease. In this issue of Journal of Clinical Oncology, Wiklund et al report an elegant study of the risk of bilateral kidney cancer. In this population-based study from Norway and Sweden, the authors defined the risk of development of bilateral kidney cancer in 28,642 patients observed for an average of 4.4 years. They found asynchronous renal cell cancer in 86 patients. One hundred twelve metachronous bilateral kidney cancer cases were detected during 126,493 person years of follow-up, revealing an overall relative risk of 3.1, with a cumulative incidence of 0.85 after 20 or more years of follow-up. A striking observation in the current work was the finding of a significant increase in relative risk of bilateral disease for young patients diagnosed with this kidney cancer. When compared with the general population, Wiklund et al found a 90% increase in risk for contralateral disease when a patient 60 years or older was diagnosed with kidney cancer, whereas in patients younger than 40 years of age, there was an 1,800% increased risk for the development of cancer in the remaining kidney. This article raises a number of important issues in the evaluation and management of patients with kidney cancer. Does bilateral disease represent metastasis of the cancer from one kidney to the other, or does it result from a genetic predisposition? In some patients with widespread metastatic disease, metastases may account for tumors in the contralateral kidney. However, in the great majority of patients, the multiple/bilateral tumors seem to arise independently, as occurs in a number of the inherited forms of kidney cancer, such as von HippelLindau (VHL) and Birt-Hogg-Dube syndrome (Table 1). It is also likely that in most instances of nonfamilial bilateral, multifocal kidney cancer, the tumors arise independently. Wiklund et al report on the incidence of bilateral kidney cancer; however, because of the magnitude and nature of this large study, the authors were not able to categorize the tumors by histologic type or to assess the prevalence of multifocality within an individual kidney. If a tumor is bilateral, it is, by definition, multifocal. The nature of this large study likely underestimates the true incidence of bilateral kidney cancer (given that the surveillance was limited to 4 years) and it is likely that in many of the patients there was occult intrarenal multifocality. The finding of bilateral tumors in such a large percentage of patients with this disease suggests that these patients have a genetic predisposition to develop renal cell cancer, and that a single gene alteration is responsible for the development of each of the tumors. This raises the possibility that many patients carry a hereditary predisposition to develop kidney tumors, and their management should be based on the expectation that additional kidney tumors may develop in these patients. If so, removing the entire kidney may be suboptimal, because much of the remaining kidney at the time of surgery may be disease free and functional, and it may be needed in the future. It has been estimated that 5% to 10% of renal cancers are hereditary. However, 5% to 10% is most likely a significant underestimate of the true hereditary predisposition to renal cancer Important insight into this question comes from the study of Gudbjartsson et al, who studied all patients in Iceland who had renal cancer from 1955 to 1999. When Gudbjartsson et al evaluated whether these individuals with kidney cancer had a relative with kidney cancer, they found a much higher risk in first-degree relatives as well as a significantly higher risk for renal cancer in members of the extended family of an affected individual. The Icelandic study suggests that there may be a genetic predisposition in nearly 60% of patients with kidney Table 1. Hereditary Renal Cancer Syndromes" @default.
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• W2137128518 date "2009-08-10" @default.
• W2137128518 modified "2023-10-04" @default.
• W2137128518 title "Genetic Basis of Bilateral Renal Cancer: Implications for Evaluation and Management" @default.
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• W2137128518 doi "https://doi.org/10.1200/jco.2009.23.0045" @default.
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