PROGNOSTIC-SIGNIFICANCE OF DNA CONTENT IN BLADDER-CANCER BASED ON FLOW CYTOMETRIC ANALYSIS OF 249 TRANSITIONAL-CELL CARCINOMAS

The prognostic significance of DNA index (DI), S-phase fraction, and h eterogeneity determined by flow cytometric DNA analysis was assessed i n a prospective study of 249 newly diagnosed transitional cell carcino mas of the bladder, The median observation time was 4.8 years. A total of 456 subpopulations were detected. The S-phases could be estimated in 299 subpopulations. A DI > 1.25 or an S-phase above 9.7% were stron gly correlated to invasiveness. One hundred and ten patients were trea ted with transurethral resection (TUR). Relapse-free survival could no t be predicted by the DNA-derived parameters, Univariate analysis of s urvival showed prognostic significance of diploidy (0.98 < DI less tha n or equal to 1.02, P = 0.02), hypotetraploidy (1.50 < DI less than or equal to 1.96, P = 0.002), and S-phase size (P = 0.008). Multivariate analysis pointed to the T-classification (RR = 1.64) and hypotetraplo idy (RR = 1.57) as prognostic parameters for survival of TUR-treated p atients. One hundred and thirty-nine patients received radiotherapy (R T). A significantly better response was found for tumors with a subpop ulation with a hypertetraploid DNA content (DI > 2.04, P = 0.05), and a significantly worse response for subpopulations with a maximum S-pha se > 24.5% (P = 0.04). T-classification and histological grade had no predictive value. A logistic regression analysis indicated an estimate d probability of response to RT of 77% for tumors with a DI > 2.04 and an S-phase < 24.5%, whereas tumors with a DI < 2.04 and an S-phase > 24.5% had only a 28% probability of response. The poor response to RT, predicted by an S-phase > 24.5%, translated into a poor survival, whe reas the better treatment response found for patients with a DI > 2.04 did not result in a longer survival, Multivariate analysis pointed to S-phase (RR = 1.70), T-classification (RR = 1.60), and grade (RR = 0. 65) as independent prognostic parameters for survival of RT-treated pa tients. (C) 1995 Wiley-Liss, Inc.