Objectives:  Cigarette smoking is a well known risk factor for the development of renal cell carcinoma (RCC); however, its association with tumor aggressiveness and patient outcome remains in question. Herein, we test the hypothesis that cigarette smoking is associated with a more aggressive phenotype and poorer outcome among patients with RCC.

Methods:  We examined data on 2242 patients treated with radical nephrectomy or nephron‐sparing surgery for unilateral, sporadic, clear cell RCC at Mayo Clinic Rochester between 1970 and 2002. Associations of self‐reported smoking status with death from RCC were assessed using Cox proportional hazards regression models summarized with hazard ratios (HR) and 95% confidence intervals (CI).

Results:  While former cigarette smoking was not associated with an increased risk of RCC death, current cigarette smokers were 31% more likely to die from RCC compared with non‐smokers on a hazard ratio scale (HR 1.31; 95% CI 1.09–1.58; P = 0.004). Interestingly, current smokers were more likely to present with advanced disease (i.e. later TNM stage) compared with both former and never smokers. After adjustment for TNM stage group and tumor grade, there was no longer a statistically significant increase in the risk of death from RCC for current cigarette smokers (HR 0.99; 95% CI 0.82–1.19; P = 0.875).

Conclusions:  Patients who report current smoking at time of surgery are at increased risk of RCC death; however, this association is attenuated after adjustment for standard pathological indices and is therefore of little prognostic value. Nevertheless, the association of current smoking with more advanced disease at presentation (e.g. metastatic spread) warrants further investigation.