The prognostic significance of S-phase analysis in stage Ta/T1 bladder cancer - A Southwest Oncology Group Study

Objectives: An intergroup study (SWOG 8795) comparing two forms of adjuncti ve therapy (immuno and chemo), bacillus Calmette-Guerin (BCG) and mitomycin C (MMC), furnished preregistration index tumors for 244 patients with supe rficial, papillary stage Ta/T1 TCC. These were examined by flow cytometry t o learn whether DNA ploidy or proliferation (low vs high S-phase fraction ( SPF) helped to predict disease recurrence or progression. Methods: Cell cycle analysis using commercially available (Multicycle) prog rams was performed on 249 Ta/T1 bladder cancers. Tumor grade, available for 223 cases, was assigned by a single study pathologist. The SWOG statistica l office reviewed follow-up information and other data and performed statis tical analysis. Results: Disease recurrence occurred in half the cases studied. The most pa rsimonious model predictive of recurrence included only treatment arm and t umor grade, with the MMC arm and tumor grade greater than I indicating wors e prognosis (p = 0.014). Neither ploidy nor SPF predicted recurrence-free s urvival or contributed prognostic information that was additive to tumor gr ade. Within 5 years of follow-up, disease progression or death from bladder cancer occurred for 29/223 (13%) of patients. The most parsimonious model for progression-free survival included only grade greater than I (p< 0.001) and high SPF (p = 0.029) (relative risk: tumor grade, 4.3, high SPF, 1.9). Conclusions: Knowledge of tumor proliferation (low versus high SPF) contrib utes prognostic information about tumor progression that is additive to tum or grade. Copyright (C) 2000 S. Karger AG. Basel.