S-phase – an independent prognostic marker in upper tract urothelial carcinoma

Abstract

Objectives To evaluate S-phase fraction as a predictor of invasiveness and cancer-specific survival in upper tract urothelial carcinoma (UTUC). Patients and methods One hundred and fifteen patients having undergone radical nephroureterectomy were analysed with histology in radical nephroureterectomy specimens as reference test and S-phase fraction as index test. Ploidy and S-phase were determined using flow cytometry. Differences in S-phase fraction were calculated between stages, grades (WHO 1999 and 2004 classifications), ploidy and patients that died of UTUC and those who did not. Five- and 10-year-cancer-specific survivals were calculated. Areas under the ROC curve (AUCs) of S-phase fraction in relation to tumour stage and to death from UTUC were measured. Multiple Cox regression was performed. Results Independent prognostic markers of death from UTUC were S-phase fraction and stage. Correlation between S-phase fraction and risk of dying from UTUC was strong, with a 17% greater risk of death from UTUC with every 1% increase in S-phase fraction, hazard ratio = 1.17, 95% CI = 1.10–1.25, p < 0.001, Spearman’s rho ρ = 0.65. AUCs for S-phase fraction as predictors of stage and death from UTUC were 0.8 (95% CI = 0.705–0.894) and 0.77 (95% CI = 0.67–0.87), respectively. Cancer-specific survival was statistically significantly different between stages, ploidy and WHO 1999 grades, but not between WHO 2004 grades. This was also reflected in S-phase fraction, which differed in LG-G1 compared with LG-G2 and in HG-G2 compared with HG-G3. Conclusion S-phase fraction was a good test for predicting both invasiveness and cancer-specific survival. Using both WHO 1999 and 2004 classifications, rather than one system alone, had a higher predictive value of cancer-specific survival.