• Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX. Electronic address: yair.lotan@utsouthwestern.edu.
• Department of Urology, University of Texas MD Anderson Cancer Center, Houston, TX.
• Department of Urology, Medical University of Vienna, Vienna, Austria.
• Department of Urology, University of Iowa Hospitals and Clinics, Iowa City, IA.
• Academic Department of Urology, AP-HP, Hopital Pitié-Salpétrière, Paris, France; UPMC Univ Paris 06, GRC5, ONCOTYPE-Uro, Institut Universitaire de Cancérologie, Paris, France.
• Department of Urology, Centre Hospitalier Universitaire de Rennes, Rennes, France.
• Department of Urology, University of Texas Southwestern Medical Center, Dallas, TX.

PURPOSE: Current knowledge regarding risk of renal-cell carcinoma (RCC) is based on meta-analyses of case-control studies. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening Trial and National Lung Screening Trial (NLST) provide robust prospective databases with clinical information and rates of cancer development. PLCO and NLST were used to identify risk factors for RCC.

METHODS: Data were extracted from PLCO and NLST to stratify risk of RCC by sex, race, age at inclusion, obesity, and smoking status. Incidence rates between groups were compared using the chi-square test. We excluded urothelial carcinomas.

RESULTS: Overall, 701/154,118 and 190/53,242 RCCs were detected in PLCO and NLST, respectively. Incidence rates were higher in men (PLCO: 0.56 vs. 0.28/1000 person y, NLST: 0.73 vs. 0.35/1000 person y; both with P<0.0001). In the PLCO, male sex, age>60 years, obesity, and intensity of smoking were associated with higher risk of developing RCC. In the NLST, sex and morbid obesity increased the risk for RCC but age, ethnicity, and smoking intensity were not predictors. There was no effect of screening for other cancers on detection of RCC. High-grade (grades ≥3) RCCs were diagnosed in 145 (20.7%) and 60 (31.6%) in the PLCO and NLST. In PLCO, age (60-64y), male sex, obesity, and current smokers with>50 pack years were at increased risk for high-grade RCC. In NLST, only male sex was an independent predictor of high-grade RCC.

CONCLUSIONS: Age over 60 years, male sex, smoking intensity, and obesity affect the risk of RCC. Identification of a high-risk population may allow a pilot study of rational screening for RCC.