Cumulative smoking exposure impacts oncologic outcomes of upper tract urothelial carcinoma

Background: The impact of cumulative smoking exposure (CSE) on oncologic outcomes for upper tract urothelial carcinoma (UTUC) remains understudied. We examined the effect of this factor on oncologic outcomes in UTUC patients undergoing radical nephroureterectomy utilizing a large contemporary multicenter, multinational cohort. Methods: Multicenter review of 1,730 patients across 17 institutions. A total of 1,041 patients met selection criteria: nephroureterectomy for urothelial carcinoma without variant histology and complete pathologic and smoking data. Smoking exposure was stratified as light, moderate, or heavy by cigarettes per day and years smoking based on prior studies. Cancer-specific (CSS) and overall survival (OS) were assessed using Kaplan–Meier and multivariable hazards models. A sub-analysis examined the effect of smoking cessation on survival stratified by CSE. Results: Median follow-up (IQR) was 24 (10–48) months. Light CSE was equal to a median of 2.0 pack years smoked, moderate CSE was equivalent to 13.0 pack years, and heavy CSE was equivalent to 40 pack-years. Five-year CSS and OS were 97% and 91% in nonsmokers, 96% and 89% with light exposure, 85% and 66% with moderate exposure, and 75% and 60% with heavy exposure. On multivariable hazards models, both moderate and heavy smoking exposure were associated with worse CSS and OS compared to nonsmokers. Smoking cessation was not associated with improved survival outcomes among patients with moderate or heavy CSE. Conclusions: Increasing CSE was associated with worse general health and oncologic outcomes in this UTUC cohort. Smoking cessation can modulate cancer outcomes up to certain thresholds of smoking exposure, emphasizing the need for both early smoking cessation and continued aggressive cancer treatment in patients with UTUC.