Individual patient risk of progression of urinary bladder papillary tumors estimated from biomarkers at initial transurethral resection of bladder tumor.

Abstract

To determine if individual, instead of group, patient progression risk could be predicted using p53, Ki67 and CK20 biomarker percentage values at initial transurethral resection of bladder tumor specimens. This was an observational study where biomarkers were measured with no knowledge of tumor outcome. Initial bladder tumor specimens were classified as non-invasive and invasive to sub-epithelium (pT1). Percentages of stained biomarker cells were tested as progression predictors from non-invasive to pT1 and pT1 to pT2. Progression probability was correlated with biomarker percentages resulting in a regression equation. We studied 112 patients (median age = 67, range 37-91, males 83/112 (73%), with median follow-up of 39months (range 1.7-140). Mean biomarker values were higher in stage pT1 than in non-invasive (all p < 0.001). Cut-off points separating progression from non-progression groups in stage pT1 were higher than in non-invasive for all biomarkers. Correlation R values for progression probability vs. biomarker percentages varied from 0.7 to 0.9 (all p < 0.001), regression slopes from 0.1 to 0.8 and intercepts from 11 to 35. A novel individual progression probability was calculated as the product of biomarker percentage of stained cells and slope, plus the prevalence-adjusted intercept. Identification of individual risk of progression in patients with non-muscle-invasive bladder tumors was possible using p53- and Ki67-derived progression probability using a regression equation. Combining biomarker-derived progression probability to tumor stage pT1 improves progression to pT2 predictive accuracy.