San Antonio, Texas USA (UroToday.com) In this session, Dr. Bellmunt discussed a more targeted approach in the treatment of T1 bladder cancer. His goal was to help generate hypotheses to inform future clinical trial design focused on proper risk stratification at initial diagnosis (not only stage and grade), early identification of patients with high risk of progression, and optimization of follow-up schema.
Dr. Bellmunt described his work in identifying patients who are likely to be progressors versus those with comparatively good outcomes (i.e. those cured by transurethral resection). In most circumstances, deletion of the tumor suppressor gene p53 was associated with progression and poor outcome. Conversely, the presence of the oncogene Rb was less associated with progression and more commonly seen in patients with good outcomes. Other genes that were first identified in The Cancer Genome Atlas (TCGA) project as bad actors were SOX4 and E2F3, and these genes were also associated with a phenotype more likely to progress in Dr. Bellmunt’s work. Moreover, tumors with features consistent with a micropapillary subtype were more likely to progress and were most similar to luminal uroplakin in the muscle-invasive subtypes from TCGA. Lastly, RNA and epigenetic techniques have also been used to stratify the T1 population into likely progressors versus comparatively better phenotypes.
Dr. Bellmunt concluded by noting that clinico-pathologic markers predicting progressive disease and recurrence have been identified. The overall mutation rates in patients who have recurrences appear to be lower than patients with good outcomes (cured by transurethral resection) and progressors. Genomic alterations in the cell cycle pathway are the main drivers of progressive disease in high-grade T1 bladder cancer. These data set the stage for inclusion of genetic and epigenetic information for clinical trial eligibility criteria and ultimately may influence treatment decisions.
Presented By: Joaquim Bellmunt, MD, PhD
Written By: Benjamin T. Ristau, MD, Society of Urologic Oncology Fellow, Fox Chase Cancer Center
17th Annual Meeting of the Society of Urologic Oncology - November 30 -December 2, 2016 – San Antonio, Texas USA