Gender-specific effect of smoking on upper tract urothelial carcinoma outcomes.

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 (≤19 CPD and ≤19.9 years), moderate (all combinations except light short-term and heavy long-term), and heavy long-term (≥20 CPD and ≥20 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 ≤ 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.

Predictors of survival in patients with soft tissue surgical margin involvement at radical cystectomy.

BACKGROUND: The presence of positive soft tissue surgical margins (STSM) at radical cystectomy (RC) is rare. Although some patients with STSM experience disease recurrence rapidly, some have long-term local disease control. We sought to describe the oncologic outcomes, identify predictors, and assess the impact of location and multifocality in patients with positive STSMs at RC. METHODS: We retrospectively collected the data of 4,335 patients treated with RC and pelvic lymphadenectomy at 11 academic centers from 1981 to 2008. STSM was defined as the presence of tumor at inked areas of soft tissue on the RC specimen. Univariate and multivariate Cox regression models addressed recurrence-free survival and cancer-specific survival after surgery. RESULTS: STSM were identified in 231 patients (5%). Actuarial recurrence-free survival estimates at 2 and 5 years after RC were 26 ± 3 and 21 ± 3%, respectively. Actuarial cancer-specific survival estimates at 2 and 5 years after RC were 33 ± 3 and 25 ± 4%, respectively. Higher body mass index (p = 0.050), higher tumor stage (p = 0.017), presence of grade 3 disease (p = 0.046), lymphovascular invasion (p = 0.003), and lymph node involvement (p = 0.003) were all independently associated with disease recurrence. Furthermore, higher tumor stage (p = 0.015), lymphovascular invasion (p = 0.006), and lymph node involvement (p = 0.006) were independently associated with cancer specific mortality. Location and multifocality of STSM were not associated with outcomes. CONCLUSIONS: Although most patients with STSM at RC had poor outcomes, more than one-fifth had durable cancer control. Pathologic features associated with disease recurrence in the general RC population also stratify patients with STSM into differential risk groups.

Impact of smoking on outcomes of patients with a history of recurrent nonmuscle invasive bladder cancer.

PURPOSE: We investigated the effects of cigarette smoking status, cumulative exposure and time from cessation on disease recurrence and progression in patients with a history of recurrent nonmuscle invasive bladder cancer. MATERIALS AND METHODS: A total of 390 patients with recurrent nonmuscle invasive bladder cancer were treated with transurethral resection of the bladder, of whom 159 (41%) received instillation therapy immediately postoperatively and 73 (19%) received adjuvant intravesical immunotherapy or chemotherapy. Smoking history included smoking status, number of cigarettes per day, smoking duration in years and years since smoking cessation. Cumulative smoking exposure was categorized as light short-term--19 or fewer cigarettes per day and 19.9 years or less, moderate--all combinations except light short-term and heavy long-term, and heavy long-term--20 or greater cigarettes per day and 20 years or greater. RESULTS: A total of 91 (23%), 192 (49%) and 107 patients (28%) were never, former and current smokers, respectively. Of ever smokers 56 (19%), 156 (52%) and 87 (29%) were light short-term, moderate and heavy long-term smokers, respectively. There was no difference in the risk of disease recurrence and progression among current, former and never smokers. On univariable analyses in ever smokers the risk of disease recurrence and progression increased with augmented smoking intensity (p ≤ 0.015), duration (p <0.001) and cumulative exposure (p <0.001). On multivariable analyses cumulative smoking exposure was an independent risk factor for disease recurrence and progression (p ≤ 0.003). Smoking cessation greater than 10 years before treatment was independently associated with decreased disease recurrence compared to current smoking (HR 0.4, p <0.001). In addition, current smokers had worse survival than former smokers, who in turn had worse survival than never smokers (p >0.05). CONCLUSIONS: There is a dose-response relationship of smoking exposure and smoking cessation with disease recurrence and progression in ever smokers with a history of recurrent nonmuscle invasive bladder cancer. These findings support counseling on smoking cessation benefits.