Gender‐specific effect of smoking on upper tract urothelial carcinoma outcomes

Abstract

Objective• To evaluate the gender-specific differential effects of smoking habits and cumulative smoking exposure on outcomes in patients with upper tract urothelial carcinoma (UTUC) treated with radical nephroureterectomy (RNU). Patients and Methods• A total of 864 consecutive patients, comprising 553 (64%) men and 311 (36%) women, from five international institutions underwent RNU without neoadjuvant chemotherapy.• Smoking history included smoking status (current, former or never), quantity of cigarettes per day (CPD), smoking duration in years and years since smoking cessation. Cumulative smoking exposure was categorized as light short-term (Յ19 CPD and Յ19.9 years), moderate (all combinations except light short-term and heavy long-term), and heavy long-term (Ն20 CPD and Ն20 years).• Uni-and multivariable competing risk regression models were used to assess the associations with outcomes. Results• Overall, 244 (28.2%), 297 (34.4%) and 323 (37.4%) patients were never, former and current smokers, respectively.• There were no differences in smoking status, quantity and duration between the genders.• In female ever smokers, 30 (9.6%), 121 (38.9%) and 67 (21.5%) were light short-term, moderate and heavy long-term smokers, respectively. Compared with men, female current smokers were more likely to experience disease recurrence in univariable analysis (P = 0.013).• In heavy long-term smokers, female gender was significantly associated with disease recurrence (hazard ratio [HR] 1.7; P = 0.03) and cancer-specific mortality (HR 2.0; P = 0.009) in multivariable analysis that adjusted for standard clinico-pathological features.• In female patients only, smoking quantity, duration and cumulative exposure were associated with disease recurrence and cancer-specific mortality on multivariable analyses (P Յ 0.025). Conclusions• The impact of smoking on UTUC outcomes after RNU is gender-specific.• Females who are current and heavy long-term smokers experience worse outcomes than their male counterparts. • Further research is needed to elucidate the molecular mechanisms underlying the gender-specific differential effect of smoking on UTUC outcomes.

Conditional Survival After Radical Nephroureterectomy for Upper Tract Carcinoma

“…However, no significant association has been identified between gender and CSS when assessing the initial postoperative risk [2]. Other studies have suggested that women could have decreased CSS when stratifying gender analyses by age or smoking habits [22,23]. Our findings highlighted that, although gender did not have an impact on CSS at baseline, female sex was an independent risk factor of poorer long-term CSS rates in >3-yr survivors.…”

Epidemiology of urothelial carcinoma

“…20 The effects of smoking on the age at the diagnosis of UTUC remain controversial. [21][22][23] In Japan, the mean age at the diagnosis of UTUC is approximately 5 years earlier for current smokers compared with current non-smokers (P < 0.0001). 24 It should also be noted that the impact of smoking on UTUC outcomes seems to be gender-specific.…”

“…Women who are current and heavy long-term smokers were reported to have worse survival outcomes than their male counterparts. 23 …”

Impact of smoking on perioperative outcomes after major surgery

“…Furthermore, the quantity of cigarettes per day and smoking duration were not captured separately and therefore, we could not use previously validated smoking status classifications such as the ''cumulative smoking exposure.'' 30 In addition, the accuracy of smoking cessation in the NSQIP has not been quantified or validated. Moreover, several surgical confounders, such as surgeon volume, surgical technique, and tumor characteristics, are not accounted for in the NSQIP.…”