Prognostic significance of dna content in bladder cancer based on flow cytometric analysis of 249 transitional cell carcinomas

Abstract

The prognostic significance of DNA index (DI), S‐phase fraction, and heterogeneity determined by flow cytometric DNA analysis was assessed in a prospective study of 249 newly diagnosed transitional cell carcinomas 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 strongly correlated to invasiveness. One hundred and ten patients were treated with transurethral resection (TUR). Relapse‐free survival could not be predicted by the DNA‐derived parameters. Univariate analysis of survival showed prognostic significance of diploidy (0.98 < DI ≤ 1.02, p = 0.02), hypotetraploidy (1.50 < DI ≤ 1.96, P = 0.002), and S‐phase size (P = 0.008). Multivariate analysis pointed to the T‐classification (RR = 1.64) and hypotetraploidy (RR = 1.57) as prognostic parameters for survival of TUR‐treated patients. One hundred and thirty‐nine patients received radiotherapy (RT). A significantly better response was found for tumors with a subpopulation with a hypertetraploid DNA content (DI > 2.04, P = 0.05), and a significantly worse response for subpopulations with a maximum S‐phase > 24.5% (P = 0.04). T‐classification and histological grade had no predictive value. A logistic regression analysis indicated an estimated 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, whereas 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 patients.