Commentary on "Smoking negatively affects renal cell carcinoma overall and cancer-specific survival." Kroeger N, Klatte T, Birkhäuser FD, Rampersaud EN, Seligson DB, Zomorodian N, Kabbinavar FF, Belldegrun AS, Pantuck AJ, Institute of Urologic Oncology, David Geffen School of Medicine at the University of California-Los Angeles, Los Angeles, CA: Cancer 2012;118(7):1795-802 (Epub 2011 Aug 25).

Tobacco use is a leading cause of premature death, yet few studies have investigated the effect of tobacco exposure on the outcome of patients with renal cell carcinoma (RCC). The authors of this report retrospectively studied the affect of smoking on clinicopathologic factors, survival outcomes, and p53 expression status in a large cohort of patients with RCC. Eight hundred and two patients (457 nonsmokers and 345 smokers) who had up to 232 months of follow-up were compared for differences in their clinicopathologic features and survival outcomes. Immunohistochemical differences in p53 expression were correlated with smoking status. Smokers presented more commonly with pulmonary comorbidities (P <0.0001) and cardiac comorbidities (P = 0.014) and with a worse performance status (P = 0.031) than nonsmokers. Smoking was associated significantly with tumor multifocality (P = 0.022), higher pathologic tumor classification (P = 0.037), an increased risk of bulky lymph node metastases (P = 0.031), and the presence of distant metastases (P <0.0001), especially lung metastases (P <0.0001). Both overall survival (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 patients who smoked. The number of pack-years was retained as an independent predictor of CSS and overall survival in patients with nonmetastatic disease. Mean expression levels of p53 were significantly higher in current smokers compared with former smokers and nonsmokers (P = 0.012). In patients with RCC, a history of smoking was associated with worse pathologic features and survival outcomes, and with an increased risk of having mutated p53. Further investigation of the genetic and molecular mechanisms associated with decreased CSS in patients with RCC who have a history of smoking is indicated.