1653 AN ANGIOGENESIS-MARKER PANEL PREDICTS NONINVASIVE PAPILLARY BLADDER CANCER RECURRENCE AT INITIAL PRESENTATION

INTRODUCTION AND OBJECTIVES: Tumor grade is currently the best predictor of noninvasive papillary (Ta) bladder cancer outcome at first presentation. This study investigated the role of angiogenic markers in predicting Ta bladder cancer outcome, under the hypothesis that angiogenesis plays a role in Ta tumor recurrence and progression. METHODS: Whole genome analysis was performed on frozen cold cup biopsies from 138 patients with Ta G2/3 bladder tumors at initial presentation on the Illumina Sentrix platform. 33 (24%), 76 (55%) and 29 (21%) patients did not recur, recurred and progressed to a higher T-stage during follow up. Adequate follow up ensured that patients likely to recur/progress did so by the end of the reporting period. 803 candidate angiogenesis-related genes were identified by GeneCards (v2.42). Mann-Whitney-U test examined associations of individual genes with outcome. Hierarchical clustering and log rank analysis was used to examine the discriminatory potential of the final gene panel for recurrence and progression. RESULTS: Median follow up of patients who never recurred (n 33) and never progressed (n 109) was 7.7 and 5.9 years, respectively. To identify genes predictive of recurrence, profiles of patients who never recurred (n 33) were compared to those who recurred and/or progressed (n 105). Mann-Whitney-U test identified 270 genes that could individually predict recurrence in this cohort (all p 0.05). To identify genes predictive of progression, profiles of patients who never progressed (n 109) were compared to those who progressed (n 29). 50 genes that were individually predictive for progression were identified (all p 0.05). 18 genes were found to be common between these two panels and were selected for the final analysis. Hierarchical clustering using the 18-gene panel identified six patient groups with varying risks of recurrence and progression. Log rank analysis showed that the 18-gene panel could significantly discriminate between patients with varying risk for recurrence (p 0.037), although its ability to do the same for progression fell short of statistical significance (p 0.16). CONCLUSIONS: Profiling angiogenic molecules is a promising approach for predicting Ta bladder tumor outcome at initial diagnosis. The 18-gene panel was able to categorize patients into several risk strata based on recurrence risk. Examining the interplay of angiogenic markers with other pathways may be essential to identify panels for progression. Such panels can help differentiate between patients who need aggressive versus expectant management.