Cost-Effectiveness Analysis of Nivolumab Plus Ipilimumab Combination Therapy as First-line Treatment for Advanced Renal Cell Carcinoma in Japan.

OBJECTIVES: The purpose of this study is to examine the cost-effectiveness of nivolumab (NIVO) plus ipilimumab (IPI) combination therapy (NIVO + IPI) compared with the sunitinib (SUN) therapy for Japanese patients with advanced renal cell carcinoma from the perspective of a Japanese health insurance payer. METHODS: A lifetime horizon was applied, and 2% per annum was set as the discount rate. The threshold was set as $ 75 000 per quality-adjusted life-year (QALY) gained. For the analytical method, we used a partitioned survival analysis model to estimate the incremental cost-effectiveness ratio (ICER), which is calculated by dividing incremental costs by incremental QALYs. Progression-free survival, progressive disease, and death were set as health states. Additionally, cost parameters and utility weights were set as key parameters. We set the intermediate/poor-risk population as the base case. Scenario analysis was conducted for the intention-to-treat population and the favorable risk population. Furthermore, one-way sensitivity analysis and probabilistic sensitivity analysis were conducted for each population. RESULTS: In the base-case analysis, the QALYs of NIVO + IPI and SUN were 4.32 and 2.99, respectively. NIVO + IPI conferred 1.34 additional QALYs. Meanwhile, the total costs in the NIVO + IPI and SUN were $692 288 and $475 481, respectively. As a result, the ICER of NIVO + IPI compared with SUN was estimated to be $162 243 per QALY gained. The parameter that greatly affected the ICER was the utility weight of progression-free survival in NIVO + IPI. CONCLUSIONS: NIVO + IPI for advanced renal cell carcinoma seems to be not cost-effective compared with the SUN in the Japanese healthcare system.

Research progress on advanced renal cell carcinoma.

Renal cell carcinoma (RCC) is a malignant tumor and the third most common urinary disease. It was estimated that RCC affected over 350,000 individuals in 2013, and there are nearly 140,000 deaths annually due to this disease. The initial masses in RCC patients are mostly confined to a single organ. However, due to the metastatic spread of cancer cells through the circulatory system, more than 30% of RCC patients relapse after surgery. The appearance of distant metastases often means that patients enter the advanced stage of cancer with low quality of life and a short expected survival time. This review aims to describe the extant research on advanced RCC, including its pathophysiology, heterogeneity, diagnosis, treatment, and prospects. We try to highlight the most suitable means of treating advanced RCC patients, focusing on comprehensive personalized treatments.

The economic burden of cancer attributable to obesity in Korea: A population-based cohort study.

OBJECTIVE: Cancer is a major cause of the burden of disease, and obesity is widely recognised one of the most important modifiable risk factor of cancer. Considering the economic impact of obesity and cancer, it is necessary to measure the economic burden of cancer attributable to excess body mass index (BMI). METHODS: This study used medical check-up sample cohort data of National Health Insurance Service (NHIS) claims and during 2002-2015. To estimate the costs (direct and indirect) according to obesity-related cancer sites, we performed a Cox proportional hazard model and cost of illness (COI) methods. RESULTS: Among male obesity-related cancer sites, the largest total costs caused by overweight or obesity were 5.5 trillion USD for liver cancer, 1.8 trillion USD for colorectal cancer and 1.6 trillion USD for kidney cancer. Among women, post-menopausal breast, liver and colorectal cancers had the largest total costs attributable to excess BMI (breast: 3.7 trillion USD, liver: 2.3 trillion USD, colorectal: 2.1 trillion USD). CONCLUSIONS: Approximately, 4.5% and 15.8% of total costs in obesity-related cancers can be reduced in men and women respectively. This study's findings highlight the importance of improved interventions, which can yield healthier lives and economic benefits beyond simply reducing cancer incidence and mortality.

Solid Renal Masses in Transplanted Allograft Kidneys: A Closer Look at the Epidemiology and Management.

The objective of this review is to explore the available literature on solid renal masses (SRMs) in transplant allograft kidneys to better understand the epidemiology and management of these tumors. A literature review using PubMed was performed according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) methodology. Fifty-six relevant studies were identified from 1988 to 2015. A total of 174 SRMs in 163 patients were identified, with a mean tumor size of 2.75 cm (range 0.5-9.0 cm). Tumor histology was available for 164 (94.3%) tumors: clear cell renal cell carcinoma (RCC; 45.7%), papillary RCC (42.1%), chromophobe RCC (3%), and others (9.1%). Tumors were managed by partial nephrectomy (67.5%), radical nephrectomy (19.4%), percutaneous radiofrequency ablation (10.4%), and percutaneous cryoablation (2.4%). Of the 131 patients (80.3%) who underwent nephron-sparing interventions, 10 (7.6%) returned to dialysis and eight (6.1%) developed tumor recurrence over a mean follow-up of 2.85 years. Of the 110 patients (67.5%) who underwent partial nephrectomy, 3.6% developed a local recurrence during a mean follow-up of 3.12 years. The current management of SRMs in allograft kidneys mirrors management in the nontransplant population, with notable findings including an increased rate of papillary RCC and similar recurrence rates after partial nephrectomy in the transplant population despite complex surgical anatomy.

Diseases Associated With Exposure to Contaminants in the Water Supply at Camp Lejeune. Final rule.

The Department of Veterans Affairs (VA) amends its adjudication regulations regarding presumptive service connection, adding certain diseases associated with contaminants present in the base water supply at U.S. Marine Corps Base Camp Lejeune (Camp Lejeune), North Carolina, from August 1, 1953, to December 31, 1987. This final rule establishes that veterans, former reservists, and former National Guard members, who served at Camp Lejeune for no less than 30 days (consecutive or nonconsecutive) during this period, and who have been diagnosed with any of eight associated diseases, are presumed to have incurred or aggravated the disease in service for purposes of entitlement to VA benefits. In addition, this final rule establishes a presumption that these individuals were disabled during the relevant period of service for purposes of establishing active military service for benefits purposes. Under this presumption, affected former reservists and National Guard members have veteran status for purposes of entitlement to some VA benefits. This amendment implements a decision by the Secretary of Veterans Affairs that service connection on a presumptive basis is warranted for claimants who served at Camp Lejeune during the relevant period and for the requisite amount of time and later develop certain diseases.

Assessment of Tuberous Sclerosis Complex Associated With Renal Lesions by Targeted Next-generation Sequencing in Mainland China.

OBJECTIVE: To identify the TSC1 and TSC2 mutations in patients with tuberous sclerosis complex (TSC) associated with renal lesions, and to explore the relationship between genotypes and phenotypes. MATERIALS AND METHODS: We analyzed 43 individuals affected with TSC accompanied by renal lesions using next-generation sequencing (NGS). We also performed Sanger sequencing to validate the NGS results. RESULTS: We reported a comprehensive mutation analysis of 43 affected individuals with TSC accompanied by renal lesions using NGS. Forty-one of 43 patients (95%) had at least 1 detectable mutation in the TSC1 or TSC2 gene. We identified 14 novel nucleotide alterations, including 11 novel small mutations and 3 large-deletion mutations for the first time. Our study showed that patients with TSC2 mutations had higher frequency of hypomelanotic macules and dental enamel pits and larger angiomyolipomas (AMLs) than patient populations with non-TSC2 mutations through analysis of the correlated mutation findings with clinical features. CONCLUSION: In conclusion, patients with TSC2 mutations had higher frequency of hypomelanotic macules and dental enamel pits, along with larger renal AMLs, compared with patient populations with non-TSC2 mutations. Patients with large deletions and frameshift mutations of the TSC1 or TSC2 gene showed larger AML diameters than patients with other kinds of mutations.

Analgesic use and risk of renal cell carcinoma: A case-control, cohort and meta-analytic assessment.

Analgesics are the most commonly consumed drugs worldwide. Evidence that analgesics increase kidney cancer risk has been mixed. We investigated the association between renal cell carcinoma (RCC) and analgesic use in a large population-based case-control study and a post-trial observational cohort study. Findings were used to update a recent meta-analytic review. We analyzed data from 1,217 RCC cases and 1,235 controls in the US Kidney Cancer Study and 98,807 participants in the US Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO: n = 137 RCCs). Self-reported acetaminophen, aspirin and nonsteroid anti-inflammatory drug (NSAID) use and duration information was assessed in relation to RCC. For the US Kidney Cancer Study, we calculated odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression. For PLCO, we computed hazard ratios (HRs) and 95%CIs using Cox regression. Among case-control participants, RCC risk was associated with over-the-counter acetaminophen use (OR = 1.35, 95%CI = 1.01-1.83). There was a positive trend with increasing duration (p-trend = 0.01), with a two-fold risk for use ≥10 years (OR = 2.01, 95%CI = 1.30-3.12). No association with prescription acetaminophen use was detected. In PLCO, acetaminophen use was also associated with increased RCC risk (HR = 1.68, 95%CI = 1.19-2.39), although elevated risk was absent among the few long-term users. No association with RCC risk was detected for aspirin or NSAIDs use in either study. An association between acetaminophen use and kidney cancer was supported by meta-analytic cohort (n = 4; summary relative risk = 1.34; 95%CI = 1.13-1.59; p-heterogeneity = 0.40) and case-control (n = 9, summary OR = 1.20; 95%CI = 1.01-1.42; p-heterogeneity = 0.05) findings. In brief, acetaminophen use may increase the risk of developing RCC.

Kidney involvement in tuberous sclerosis complex: the impact on healthcare resource use and costs.

OBJECTIVE: Tuberous sclerosis complex (TSC) is associated with non-malignant kidney lesions-angiomyolipomata-that may be associated with chronic kidney disease (CKD). This study investigated the relationship between renal angiomyolipomata and CKD in TSC, including the impact on healthcare resource utilization (HCRU) and costs. METHODS: This was a retrospective, longitudinal cohort study based on medical record data spanning January 1990-April 2012 for 369 TSC patients treated at a specialty center in the Netherlands. Cohorts were established based on CKD stage and angiomyolipoma size. Rates of HCRU (physician visits, monitoring, and interventions) were compared across cohorts using rate ratios. Healthcare costs were compared across cohorts using cost differences. Regression models were used to identify predictive factors for HCRU and healthcare costs. RESULTS: Sixteen per cent of patients reached CKD stage 3 or higher during follow-up. Patients at more advanced stages of CKD more frequently had either large or multiple small angiomyolipomata and higher HCRU rates and healthcare costs. In the multivariate analyses, male gender, CKD stage >1, angiomyolipoma size ≥3.5 cm, embolization, and the presence of moderate or severe lymphangioleiomyomatosis (LAM) were associated with greater HCRU (p ≤ 0.002 for all comparisons). Definite (vs suspected) TSC diagnosis, CKD stage 5 (vs CKD stage 1), angiomyolipoma size ≥3.5 cm, and moderate or severe LAM were associated with higher costs (p = 0.050 for TSC diagnosis, p ≤ 0.002 for other comparisons). Costs in CKD stage 5 were driven primarily by dialysis. CONCLUSIONS: A substantial proportion of patients with TSC developed moderate-to-severe CKD, which was associated with renal angiomyolipomata and increased HCRU and costs.

Rates of interventional procedures in patients with tuberous sclerosis complex-related renal angiomyolipoma.

OBJECTIVE: To describe rates of renal artery embolization, partial nephrectomy, and complete nephrectomy in patients with tuberous sclerosis complex (TSC) and renal angiomyolipoma. METHODS: Data from the MarketScan® Research Databases were used to select patients with TSC and renal angiomyolipoma during January 1, 2000-March 31,2013 (Commercial database) and January 1, 2000-June 30, 2012 (Medicaid database). Patients had at least 30 days of follow-up and were followed until the earliest of inpatient death, end of enrollment, or end of study. Rates of embolization and nephrectomy were calculated. RESULTS: In total, 218 patients <18 years (mean = 9.7 years) and 378 patients ≥18 years (mean 36.9 years) were selected from the Commercial database. Fifty-nine patients <18 years (mean = 7.2 years) and 117 patients ≥18 years (mean = 37.2 years) were selected from the Medicaid database. Follow-up in the Medicaid cohorts was approximately twice that of the Commercial cohorts. Among patients in the study, 24.2% had at least one interventional procedure: 15.2% had embolization, 5.2% had partial nephrectomy, and 7.6% had complete nephrectomy. Within the Commercial cohort ≥18 years, 18.5% had embolization, 7.7% had partial nephrectomy, and 11.4% had complete nephrectomy. Corresponding percentages in the Medicaid adult cohort were 17.1%, 5.1%, and 4.3%. Repeat embolization procedures occurred in up to 7.7% of Commercial patients and in up to 6.8% of Medicaid patients. Repeat partial nephrectomy occurred in up to 4.5% and 1.7% of Commercial and Medicaid patients, respectively. CONCLUSIONS: Approximately 25% of patients with TSC-renal angiomyolipoma experienced embolization or nephrectomy, with some patients undergoing repeat procedures. Study limitations included small sample sizes, the majority of the study period occurred prior to the approval of mammalian target of rapamycin inhibitors for the treatment of TSC-renal AML, and results may not be generalizable to patients with insurance other than commercial or Medicaid.

Renal cell carcinoma in patients with acquired cystic disease of the kidney: assessment using a combination of T2-weighted, diffusion-weighted, and chemical-shift MRI without the use of contrast material.

PURPOSE: To evaluate the MRI findings of renal cell carcinoma (RCC), including findings on diffusion-weighted images (DWIs) and chemical shift images (CSIs), in patients with acquired cystic disease of the kidney (ACDK) in relation to the histopathologic findings. MATERIALS AND METHODS: Two radiologists retrospectively reviewed the MRI findings of 10 RCCs in seven consecutive patients with ACDK. They evaluated the signal intensities (SIs) and signal homogeneity of the lesions on T2-weighted images, DWIs, and T1-weighted images. Thereafter, they evaluated the cytoplasmic fat in the lesions by CSIs. After image analyses, the MRI findings were correlated with the histopathologic findings. RESULTS: The RCCs tended to show heterogeneous high SIs on T2-weighted images and DWIs. The high SIs on DWIs were mainly attributable to the viable parts, and the heterogeneity was due to the various SIs arising from the intratumoral degenerative components. Unlike the reported findings for hemorrhagic cysts, the RCCs did not show homogeneous high SIs or fluid-iron levels on T1-weighted images. The four lesions, in which the presence of cytoplasmic fat was suggested on CSIs, were clear cell RCCs. CONCLUSION: The MRI findings, including findings on DWIs and CSIs, well reflected the histopathologic findings of RCC in patients with ACDK.

An extensive epidemiological investigation of a kidney cancer cluster in a chemical plant: what have we learned?

OBJECTIVES: In 2003, a cluster of renal cell carcinoma (RCC) cases was reported among men working at a French chemical plant using a proprietary process to produce vitamin A. The 10 index cases yielded a standardised incidence ratio of 13.1 for 1994-2002. Nine of these 10 cases were diagnosed by a plant-specific abdominal ultrasonography screening programme that targeted exposure to an intermediate chemical, 4-chloro-1,1-dimethoxy-3-methyl-2-butene, commonly named 'chloracetal C5', suspected as the cause by some experts. Epidemiological investigations sought to examine the relations between occupational exposures and RCC. METHODS: A retrospective cohort mortality study and a nested case--control study were conducted. The cohort study included all workers who had been employed at the plant for at least 6 months between 1960 and 2003. The case--control study included an extensive search within the region for other kidney cancer cases among the cohort members. Industrial hygienists assessed occupational exposure. RESULTS: From 1968 to 2006, no significant excess mortality was observed for all causes of death or for all cancers. We found excess mortality for kidney cancer only among women. The nested case--control study showed a dose--response relation for cumulative exposure to chloracetal C5: the OR rose from 2.5 in the low-exposure category to 10.5 in the high-exposure group. Adjustment for screening attenuated this relation. CONCLUSIONS: The results of the case--control study were consistent with the positive results of in vivo genotoxic tests and suggest that chloracetal C5 can have a causal role in RCC.

Assessment of renal shape of horseshoe kidney with multidetector row CT in adult patients: relationship between urolithiasis and renal isthmus.

OBJECTIVE: The aim of this study was to evaluate the relationship between urolithiasis and characteristics of renal shape in adult patients with horseshoe kidney (HSK) diagnosed on multidetector row computed tomography (MDCT). METHODS: We evaluated 36 patients with HSK and urolithiasis (Group A) and 70 patients with HSK without urolithiasis (Group B) whose disease was diagnosed on non-contrast MDCT. Two radiologists measured minimum width of the renal isthmus and maximum length of the renal pelvis and evaluated coexisting neoplastic diseases on axial computed tomographic (CT) images with 5-mm reconstruction, and we compared those measurements between the Groups A and B. RESULTS: The overall mean maximum length of the renal pelvis, 12.7±9.2 mm, did not differ significantly between the 2 groups. Minimum isthmus width was larger in patients with HSK and urolithiasis (11.0±5.6 mm), than those without urolithiasis (9.5±5.1 mm). No patient in either groups had a urological renal tumor. CONCLUSIONS: Patients of HSK might have tendency of a high incidence of stone formation. Because urolithiasis is a risk factor for tumors of the renal pelvis, monitoring of patients with HSK requires careful attention to isthmus width on CT images.

Development of a clinical prediction model for assessment of malignancy risk in Bosniak III renal lesions.

OBJECTIVE: To identify independent predictors of malignancy in Bosniak III (BIII) renal lesions and to build a prediction model based on readily identifiable clinical variables. METHODS: In this institutional review board-approved, Health Insurance Portability and Accountability Act (HIPAA)-compliant retrospective study, radiology, and hospital information systems containing data from January 1, 1994, to August 31, 2009, were queried for adult patients (age >18 years) with surgically excised BIII lesions. Clinical variables and results of histopathology were noted. Univariate and multiple-variable logistic regression analyses were performed to identify potential predictors and to build a prediction model. Cross-validation was used to assess generalizability of the model's performance, as characterized by concordance (c) index. RESULTS: Of the 107 lesions in 101 patients, 59 were malignant and 48 benign. On univariate analyses, the strongest potential predictors of malignancy were African American race (P = .043), history of renal cell carcinoma (RCC; P = .026), coexisting BIII lesions (P = .032), coexisting Bosniak IV (BIV) lesions (P = .104), body mass index (BMI; P = .078), and lesion size (P <.001). A model with lesion size (odds ratio [OR] = 0.69; 95% confidence interval [CI] 0.58-0.82), history of RCC (9.02; CI 0.99-82.15), and BMI (OR 1.1; 95% CI 0.99-1.19) offered the best performance with a c-index after cross-validation of 0.719. Using an estimated probability of malignancy of >80%, the positive predictive value of the model is 92% (CI 78%-100%). CONCLUSION: Clinical risk factors offer modest but definite predictive ability for malignancy in BIII lesions. In particular, a prediction model encompassing lesion size, BMI, and history of RCC seems promising. Further refinements with possible inclusion of imaging biomarkers and validation on an independent dataset are desirable.

Hypertension and risk of renal cell carcinoma among white and black Americans.

BACKGROUND: Renal cell carcinoma and hypertension (a well-established renal cancer risk factor) are both more frequent among blacks than whites in the United States. The association between hypertension and renal cell carcinoma has not been examined in black Americans. We investigated the hypertension-renal cancer association by race, and we assessed the role of hypertension in the racial disparity of renal cancer incidence. METHODS: Participants were enrolled in a population-based case-control study in Detroit and Chicago during 2002-2007 (number of cases: 843 whites, 358 blacks; number of controls: 707 whites, 519 blacks). Participants reported their history of hypertension and antihypertensive drug use. We used unconditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusted for demographic characteristics, smoking, body mass index, and family history of cancer. RESULTS: Hypertension doubled renal cancer risk (OR = 2.0 [CI = 1.7-2.5]) overall. For whites, the OR was 1.9 (CI = 1.5-2.4), whereas for blacks it was 2.8 (2.1-3.8) (P for interaction = 0.11). ORs increased with time after hypertension diagnosis (P for trend <0.001), reaching 4.1 (CI = 2.3-7.4) for blacks and 2.6 (CI = 1.7-4.1) for whites after 25 years. ORs for poorly controlled hypertension were 4.5 (CI = 2.3-8.8) for blacks and 2.1 (CI = 1.2-3.8) for whites. If these estimates correctly represent causal effects and if, hypothetically, hypertension could be prevented entirely among persons aged 50-79 years, the black/white disparity in renal cancer could be reversed among women and reduced by two-thirds among men. CONCLUSIONS: Hypertension is a risk factor for renal cancer among both blacks and whites, and might explain a substantial portion of the racial disparity in renal cancer incidence. Preventing and controlling hypertension might reduce renal cancer incidence, adding to the known benefits of blood pressure control for heart disease and stroke reduction, particularly among blacks.

Incidence, predictors, costs, and outcome of renal cell carcinoma after kidney transplantation: USRDS experience.

INTRODUCTION: We carried out an analysis of the United States Renal Data System to determine the incidence, risk factors, prognosis, and costs associated with the diagnosis of renal cell carcinoma (RCC) after kidney transplantation. METHODS: This is a retrospective cohort of 40,821 Medicare primary renal transplant recipients transplanted from January 1, 2000, to July 1, 2005, and followed up till December 31, 2005, excluding those with prior RCC or nephrectomy. Kaplan-Meier analysis was performed to determine the time of occurrence of RCC, and Cox regression was used to determine factors associated with RCC. RESULTS: Three hundred sixty-eight patients were diagnosed with RCC within 3 years after transplant (incidence of 3.16 per 1000 person years). The 3-year incidence of RCC posttransplant was 9.29 per 1000 person years (2.3%) for those with pretransplant cysts and 3.08 per 1000 person years (0.7%) without pretransplant cysts. RCC was diagnosed disproportionately early posttransplant in patients with cysts. Cysts were independently associated with increased risk of RCC, as was male gender, older recipient, donor age, African American recipient, increased time on dialysis and acute rejection within first year posttransplant. RCC was associated with increased risk of mortality with a higher risk with pretransplant cysts. Patients who developed RCC had higher cumulative median costs ($55,456 at 2 years) than those who did not develop RCC ($40,369). There was no "clustering" of RCC in individual states or centers more than would be expected by chance. CONCLUSION: RCC was diagnosed disproportionately early in patients with pretransplant renal cysts and was associated with a worse prognosis and increased costs.

Quantitative assessment of red meat or processed meat consumption and kidney cancer.

OBJECTIVE: To conduct a quantitative assessment of red meat or processed meat consumption and kidney cancer. METHODS: We extracted data from 12 case-control studies, three cohort studies, and the Pooling Project of Diet and Cancer publication for which 13 international cohorts were evaluated. Random effects meta-analysis models were used to calculate summary relative risk estimates (SRRE) based on high vs. low intake values. Sensitivity and influence analyses were conducted, including assessments of heterogeneity. RESULTS: The SRRE for all studies that reported results for red meat (included variables labeled 'red meat' or single red meat items, such as beef, pork, or liver) was 1.12 (95% CI: 0.98-1.29; p-value for heterogeneity=0.015), and the SRRE using only data from prospective cohorts was 1.02 (95% CI: 0.91-1.15) with minimal heterogeneity (p=0.741). Similarly, in a meta-analysis of the five studies that simultaneously adjusted for smoking, BMI, and total energy intake, the SRRE for red meat was 1.02 (95% CI: 0.91-1.15). No significant association was observed in the meta-analysis of processed meat consumption (SRRE=1.07; 95% CI: 0.94-1.23), although a significant association was observed when only data from cohort studies were analyzed (SRRE=1.19; 95% CI: 1.03-1.37). CONCLUSIONS: Although many of the summary results were positive, all were weak in magnitude, most were not statistically significant, and associations were attenuated among studies that adjusted for key potential confounding factors. In summary, the findings of this meta-analysis are not supportive of an independent relation between red or processed meat intake and kidney cancer.

Metachronous bilateral renal cell carcinoma: risk assessment, prognosis and relevance of the primary-free interval.

PURPOSE: We evaluated the prognosis, risk factors and relevance of the primary-free interval in a large cohort with metachronous bilateral renal cell carcinoma. MATERIALS AND METHODS: We studied 120 patients with metachronous, bilateral renal cell carcinoma who were treated at 12 international academic centers. Logistic regression was performed to evaluate risk factors for contralateral metachronous renal cell carcinoma during followup. Disease specific survival was evaluated with univariate and multivariate analysis. RESULTS: Median age at diagnosis of the first and second renal cell carcinomas was 54 and 62 years, respectively. The most common histological subtype was bilateral clear cell renal cell carcinoma (89% of cases). Familial renal cell carcinoma was found in 14% of patients, von Hippel-Lindau disease was found in 4% and nonfamilial renal cell carcinoma was found in 81%. The 15-year disease specific survival rates for the first and second renal cell carcinomas were 66% and 44%, respectively. Logistic regression revealed von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age as independent risk factors for contralateral renal cell carcinoma after surgery for unilateral renal cell carcinoma. A longer primary-free interval was associated with a better prognosis. When calculating disease specific survival from the diagnosis of the first renal cell carcinoma, the primary-free interval was an independent prognostic factor. CONCLUSIONS: Long-term survival rates of metachronous, bilateral renal cell carcinoma are moderate. von Hippel-Lindau disease, a family history of renal cell carcinoma, multifocal first renal cell carcinoma and young patient age are independent risk factors for contralateral renal cell carcinoma. These risk factors support close and extended abdominal surveillance following nephrectomy for unilateral renal cell carcinoma. Patients with a longer primary-free interval have a more favorable prognosis.