title: 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).
  
  
  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.
authors: Weill Cornell Medical College, New York-Presbyterian Hospital, New York, NY; University Medical Center Hamburg-Eppendorf, Hamburg, Germany.
authors: Michael
authors: M
authors: Rink
authors: Evanguelos
authors: E
authors: Xylinas
authors: Quoc-Dien
authors: QD
authors: Trinh
authors: Yair
authors: Y
authors: Lotan
authors: Vitaly
authors: V
authors: Margulis
authors: Jay D
authors: JD
authors: Raman
authors: Margit
authors: M
authors: Fisch
authors: Richard K
authors: RK
authors: Lee
authors: Felix K
authors: FK
authors: Chun
authors: Joual
authors: J
authors: Abdennabi
authors: Christian
authors: C
authors: Seitz
authors: Armin
authors: A
authors: Pycha
authors: Alexandre R
authors: AR
authors: Zlotta
authors: Pierre I
authors: PI
authors: Karakiewicz
authors: Marko
authors: M
authors: Babjuk
authors: Douglas S
authors: DS
authors: Scherr
authors: Shahrokh F
authors: SF
authors: Shariat
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000401:mortality*; D009392:Nephrectomy / Q000401:mortality*; D011379:Prognosis; D012189:Retrospective Studies; D018570:Risk Assessment; D017678:Sex Distribution; D012737:Sex Factors; D012907:Smoking / Q000009:adverse effects* / Q000401:mortality; D016540:Smoking Cessation; D013997:Time Factors; D014516:Ureteral Neoplasms / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D019459:Urothelium / Q000473:pathology*
keywords: dose relationship; gender; radical nephroureterectomy; recurrence; smoking; survival; transitional cell carcinoma; upper urinary tract; urothelial carcinoma