title: Analysis of sex differences in cancer-specific survival and perioperative mortality following radical cystectomy: results of a large German multicenter study of nearly 2500 patients with urothelial carcinoma of the bladder.
abstract: BACKGROUND
  Outcome of patients with urothelial carcinoma of the bladder (UCB) varies between sexes. Although overall incidence is higher in men, cancer-specific survival (CSS) has been suggested to be lower in women. Although the former effect is attributed to greater exposure to carcinogens in men, the latter has not been elucidated.
  
  
  OBJECTIVE
  The aim of the study was to identify sex-specific outcomes based on one of the largest databases of patients with UCB who underwent radical cystectomy (RC).
  
  
  METHODS
  This retrospective multicenter series comprised 2483 patients in Stage M0 who underwent RC for UCB from 1989 to 2008; 20.4% of patients were women. The impact of sex on CSS in the entire study group and in specific subgroups was analyzed. The median follow-up time was 42 months (interquartile range, 21-79).
  
  
  RESULTS
  Histopathologic criteria of pathologic tumor (pT), pathologic nodal (pN), grade, lymphovascular invasion (LVI), and associated carcinoma in situ (CIS) of the study did not differ between sexes. The percentage of female patients increased over time. Five-year CSS in female patients was significantly lower than in male patients (60% vs 66%; P = 0.005). In multivariate analysis adjusted to other covariates, tumor stage ≥pT3 (hazard ratio [HR] = 2.44; P < 0.001), positive pN status (HR = 1.91; P < 0.001), LVI (HR = 1.48; P < 0.001), lower count of lymph nodes removed (HR = 0.98; P = 0.002), older age (HR = 1.01; P < 0.001), and female gender (HR = 1.26; P = 0.011) had an independent impact on CSS. Deterioration of CSS in female patients was pronounced when LVI was present (HR = 1.57; P < 0.001) and when RC was performed in the earlier time period (HR = 2.44; P < 0.001). However, women showed significantly lower perioperative mortality (within 90 days after RC) compared with men.
  
  
  CONCLUSIONS
  After RC for UCB, cancer-specific mortality was higher in female patients; this disadvantage was more pronounced in earlier time periods. In addition, worse outcome of women with verified LVI was shown to be comparable with men. These findings were suggestive of different tumor biology and potentially unequal access to timely RC in earlier time periods because of reduced awareness of UCB in women. Further studies are required to improve UCB outcome in both sexes, notably in female patients.
authors.affiliation: Department of Urology, Caritas St. Josef Medical Centre, University of Regensburg, Landshuterstrasse 65, Regensburg, Germany. wolfgang.otto@klinik.uni-regensburg.de
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Otto
authors.forename: Matthias
authors.initials: M
authors.lastname: May
authors.forename: Hans-Martin
authors.initials: HM
authors.lastname: Fritsche
authors.forename: Duska
authors.initials: D
authors.lastname: Dragun
authors.forename: Atiqullah
authors.initials: A
authors.lastname: Aziz
authors.forename: Michael
authors.initials: M
authors.lastname: Gierth
authors.forename: Lutz
authors.initials: L
authors.lastname: Trojan
authors.forename: Edwin
authors.initials: E
authors.lastname: Herrmann
authors.forename: Rudolf
authors.initials: R
authors.lastname: Moritz
authors.forename: Jörg
authors.initials: J
authors.lastname: Ellinger
authors.forename: Derya
authors.initials: D
authors.lastname: Tilki
authors.forename: Alexander
authors.initials: A
authors.lastname: Buchner
authors.forename: Thomas
authors.initials: T
authors.lastname: Höfner
authors.forename: Sabine
authors.initials: S
authors.lastname: Brookman-May
authors.forename: Philipp
authors.initials: P
authors.lastname: Nuhn
authors.forename: Christian
authors.initials: C
authors.lastname: Gilfrich
authors.forename: Jan
authors.initials: J
authors.lastname: Roigas
authors.forename: Mario
authors.initials: M
authors.lastname: Zacharias
authors.forename: Stefan
authors.initials: S
authors.lastname: Denzinger
authors.forename: Markus
authors.initials: M
authors.lastname: Hohenfellner
authors.forename: Axel
authors.initials: A
authors.lastname: Haferkamp
authors.forename: Stefan C
authors.initials: SC
authors.lastname: Müller
authors.forename: Arkadius
authors.initials: A
authors.lastname: Kocot
authors.forename: Hubertus
authors.initials: H
authors.lastname: Riedmiller
authors.forename: Wolf F
authors.initials: WF
authors.lastname: Wieland
authors.forename: Christian G
authors.initials: CG
authors.lastname: Stief
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Bastian
authors.forename: Maximilian
authors.initials: M
authors.lastname: Burger
mesh_terms: D000367:Age Factors; D000368:Aged; D001808:Blood Vessels / Q000473:pathology; D002277:Carcinoma / Q000401:mortality* / Q000556:secondary* / Q000601:surgery; D015653:Cystectomy; D005260:Female; D005858:Germany; D006801:Humans; D053208:Kaplan-Meier Estimate; D008207:Lymphatic Metastasis; D042601:Lymphatic Vessels / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012737:Sex Factors; D015996:Survival Rate; D001749:Urinary Bladder Neoplasms / Q000401:mortality* / Q000473:pathology* / Q000601:surgery