© 2010 THE AUTHORS 1638 JOURNAL COMPILATION © 2 0 1 0 B J U I N T E R N A T I O N A L | 1 0 6 , 1 6 3 8 – 1 6 4 2 | doi:10.1111/j.1464-410X.2010.09441.x 2010 THE AUTHORS; JOURNAL COMPILATION 2010 BJU INTERNATIONAL Urological Oncology FAMILY HISTORY OF CLEAR CELL RENAL CELL CARCINOMA TOLLEFSON ET AL. The impact of family history on pathological and clinical outcomes in non-syndromic clear cell renal cell carcinoma Matthew K. Tollefson, Stephen A. Boorjian, Christine M. Lohse † , Michael L. Blute and Bradley C. Leibovich Departments of Urology and † Health Sciences Research, Mayo Medical School and Mayo Clinic, Rochester, MN, USA Accepted for publication 18 February 2010 Dube syndrome were excluded from analysis. Demographics and clinico-pathological outcomes were compared to patients with ccRCC without a family history of kidney cancer using chi-squared and Fisher’s exact tests. Postoperative cancer-specific survival was estimated using the Kaplan–Meier method. RESULTS We identified 42 patients (1.6%) with a family history of ccRCC who were treated for non-cystic ccRCC, with a median follow-up of 4.7 years (range 1–34). Demographics and tumour characteristics, including tumour stage and grade, were similar between the two groups. Patients with a family history of ccRCC were more likely to have bilateral tumours (11.9 vs 2.2%, P = 0.003). Nevertheless, cancer-specific survival rates for patients with and without a family history of ccRCC were similar at 5 years (75.7 vs 71.1%) and 10 years (53.9 vs 62.2%). CONCLUSIONS Patients with a family history of ccRCC have pathological and clinical outcomes similar to patients with sporadic ccRCC. The increased incidence of bilateral tumours associated with a family history of ccRCC provides further evidence to support a nephron- sparing surgical approach when feasible. KEYWORDS renal cell carcinoma, family history, disease progression, partial nephrectomy Study Type – Prognosis (case series) Level of Evidence 4 OBJECTIVE To investigate the impact of family history on pathological and clinical outcomes after surgery for clear-cell renal cell carcinoma (ccRCC) in patients with non-syndromic disease. PATIENTS AND METHODS We reviewed 2677 patients treated with radical nephrectomy or nephron-sparing surgery for non-cystic ccRCC between 1970 and 2004 to identify patients with a family history of ccRCC. Patients with von Hippel– Lindau, tuberous sclerosis, or Birt–Hogg– INTRODUCTION Few human malignancies have undergone the degree of genetic study and classification that clear-cell renal cell carcinoma (ccRCC) has been subjected to over the past two decades. Due in part to its resistance to more traditional forms of cancer therapy [1], studies have focused upon the genetic nature of the disease for insight into developing novel treatments. Several familial syndromes have been identified, and the primary tumour suppressor genes and/or oncogenes responsible for the development of these conditions have been defined. Furthermore, through the study of patients with syndromic forms of ccRCC, new agents have been developed for treating patients with advanced stages of the disease [2–5]. Deletions in the short arm of chromosome 3 have been associated with the development of ccRCC and account for the most widely investigated hereditary ccRCC syndrome, von Hippel–Lindau disease (VHL) [5]. Molecular studies examining tumour DNA from sporadic cases of ccRCC have provided strong evidence that VHL alteration is a common, early event in the carcinogenic process. In addition, specific types of VHL mutations may be associated with aetiological factors, disease progression and prognosis [6,7]. In both familial and sporadic ccRCC, allelic inactivation of the von Hippel–Lindau gene has been shown to occur through loss of heterozygosity, mutation or methylation in most ccRCC tumours [8,9]. Although most patients with non-syndromic ccRCC have no family history of the malignancy, it is associated with strong genetic susceptibility. Several large population-based epidemiological studies have demonstrated a familial pattern of ccRCC incidence [10,11]. Patents with a first- or second-degree relative with ccRCC have been found to have a 2-5-fold higher incidence of the malignancy than individuals without such a family history. However, little is known regarding the prognosis, stage at presentation or risk of synchronous or metachronous disease in patients with non- syndromic, familial ccRCC. Furthermore, while management guidelines for patients with hereditary ccRCC syndromes have been outlined, the treatment and outcomes of patients with a family history of ccRCC in the absence of an established syndrome have not been well defined. BJUI BJU INTERNATIONAL