Prognostic effect of DNA aneuploidy from bladder washings in superficial bladder cancer

Cancer Epidemiol Biomarkers Prev. 2007 May;16(5):979-83. doi: 10.1158/1055-9965.EPI-06-0538.

Abstract

Background: Superficial (papillary) bladder cancer is associated with progression and death from muscle-invasive bladder cancer, but no reliable predictors of the outcomes have been identified.

Methods: We analyzed the long-term prognostic effect of DNA flow cytometry in bladder washings from 93 subjects with previously resected T(a) and T(1) bladder tumors who participated in a chemoprevention trial of the synthetic retinoid fenretinide. Kaplan-Meier analysis and Cox regression were used to determine the prognostic effect of DNA aneuploidy on cancer progression and mortality in conjunction with conventional clinical factors after a median of 11.5 years (interquartile range, 9.5-11.7 years).

Results: Overall, 58 of 93 (62%) specimens were DNA aneuploid at baseline. Progression-free survival was significantly shorter in subjects with stage T(1) [hazard ratio (HR), 31.6; 95% confidence interval (95% CI), 2.6-386.1; P < 0.001] and in subjects with baseline DNA aneuploid washing (HR, 10.5; 95% CI, 1.1-126.1; P = 0.03). The risk of death was also greater for stage T(1) tumors (HR, 2.6; 95% CI, 1.04-6.7; P = 0.04). DNA aneuploidy was a significant prognostic factor also for overall survival (HR, 2.8; 95% CI, 1.0-9.0; P = 0.05). Fenretinide treatment had no significant effect on cancer progression and death.

Conclusions: DNA aneuploidy in washings from endoscopically normal bladder is a significant predictor of progression and death in addition to tumor stage. This biomarker may help to identify and monitor a high-risk group who may benefit from a chemoprevention intervention.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aneuploidy*
  • Anticarcinogenic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Biomarkers, Tumor / genetics
  • Cohort Studies
  • DNA, Neoplasm / analysis*
  • DNA, Neoplasm / genetics
  • Disease Progression
  • Female
  • Fenretinide / therapeutic use
  • Flow Cytometry
  • Humans
  • Male
  • Middle Aged
  • Prognosis
  • Survival Analysis
  • Urinary Bladder / pathology
  • Urinary Bladder Neoplasms / genetics*
  • Urinary Bladder Neoplasms / mortality*
  • Urinary Bladder Neoplasms / prevention & control

Substances

  • Anticarcinogenic Agents
  • Biomarkers, Tumor
  • DNA, Neoplasm
  • Fenretinide