Trends in renal cell carcinoma mortality associated with tobacco use in U.S. adults aged ≥45 years, 1999–2023: A population-based CDC WONDER analysis.

434 Background: Renal cell carcinoma (RCC) is one of the common malignancies in the United States. Tobacco exposure is an established risk factor for renal cell carcinoma (RCC). Despite declining smoking prevalence in the United States, its impact on RCC mortality remains unclear. Methods: Using CDC WONDER multiple-cause-of-death data (1999–2023), we identified deaths in adults aged ≥45 years with malignant neoplasm of the kidney (C64) and tobacco use disorder (F17). Age-adjusted mortality rates (AAMR, per 100,000) were analyzed by sex, age, and Census regions. Temporal trends were assessed using Joinpoint regression to estimate average annual percent change (AAPC). Results: From 1999 to 2023, a total of 27,893 deaths were attributed to RCC and tobacco smoking among U.S. adults aged ≥45 years. The overall average AAMR was 0.84, rising from 0.06 in 1999 to 1.19 in 2023 (AAPC: 16.3%, p = 0.001). The most pronounced significant increase in AAMR occurred between 1999–2004 (APC: 72.3%, p = 0.001), followed by a continued rise through 2012 (APC: 10.4%, p = 0.001), and a non-significant increase thereafter (APC: 1%, p = 0.19). Adult males had a higher average AAMR than females (1.41 vs 0.40). From 1999 to 2023, AAMR increased significantly in both sexes, rising from 0.1 to 2.11 in males (AAPC: 13.9%, p = 0.001) and from 0.04 to 0.61 in females (AAPC: 13.6%, p = 0.001). Older adults (≥65 years) demonstrated a higher average AAMR (1.69) compared to middle-aged adults (45–64 years; 0.36). The greatest increase was seen in older adults, with AAMR rising from 0.1 to 2.59 (AAPC: 14.4%, p = 0.001). A similar significant increase was observed in middle-aged adults, from 0.04 to 0.48 (AAPC: 11.8%, p = 0.001). Across census regions, the Midwest recorded the highest average AAMR (1.23), followed by the South (0.8) and the West (0.62). The Midwest also showed the steepest increase, from 0.04 to 1.97 (AAPC: 17.4%, p = 0.001), followed by the South (0.07 to 1.25, AAPC: 14.4%, p = 0.001) and the West (0.07 to 0.85, AAPC: 14.1%, p = 0.001). Conclusions: Rising tobacco-related RCC mortality, particularly among older adults, males, and Midwestern populations, highlights persistent disparities and supports the need for strengthened prevention and early-detection strategies.