The effect of tobacco exposure in renal cell carcinoma (RCC) overall and cancer-specific survival.

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4578 Background: Tobacco use is a leading cause of premature death in the United States, yet few studies have investigated the effect of tobacco exposure on RCC outcomes. We retrospectively studied the impact of smoking history on clinicopathological factors, survival outcomes, and p53 expression status in a large cohort of RCC patients. Methods: 802 patients with ccRCC treated at UCLA formed the study cohort. Patients were divided into two groups, never smokers (457 patients) and patients with a positive tobacco exposure history (345 patients). The Kaplan Meier method and log rank test were used to evaluate survival outcomes. Cox models were constructed to evaluate independent risk factors. Immunohistochemistry (IHC) differences in p53 expression were correlated with smoking status. Results: Patients who were current smokers presented more commonly with pulmonary (p< 0.0001) and cardiac medical co-morbidities (p=0.014), and with a worse performance status (p=0.031) than non-smokers. Smoking was significantly associated with tumor multifocality (p=0.022), higher pT stages (p=0.037), increased risk of lymph node metastases (p=0.031) especially bulky N2 disease (p=0.009), presence of distant metastases (p<0.0001), especially lung metastases (p<0.0001). Both overall survival (OS 62.37 months vs. 43.64 months (p= 0.001) and cancer specific survival (CSS 87.43 months vs. 56.57 months (p=0.005) were significantly worse in the group of patients with a smoking history. In multivariate Cox models the number of pack years was retained as an independent predictor of CSS and OS in non-metastatic patients. Mutated p53 was detected in 70.8% of current and 53.0% of non-smokers, respectively (p=0.017), and mean expression was significantly higher in current versus non-smokers (p=0.012). Conclusions: In RCC patients, a history of smoking was associated with worse pathologic features and survival outcomes, and with increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in RCC patients with a smoking history are indicated.