Grant Details
Grant Number: |
5R01CA257480-03 Interpret this number |
Primary Investigator: |
Tang, Li |
Organization: |
Roswell Park Cancer Institute Corp |
Project Title: |
Transcriptomic Classification of Non-Muscle Invasive Bladder Cancer and Its Clinical and Prognostic Implication |
Fiscal Year: |
2024 |
Abstract
This study addresses the unmet clinical needs for management of non-muscle invasive bladder cancer
(NMIBC). NMIBC represents ~75% of bladder cancer cases and has a favorable five-year survival rate, but
typically recurs (50-70% in 5 years) and progresses to muscle-invasive disease (MIBC, 10-30%). Intravesical
Bacillus Calmette-Guerin (BCG) is the most effective therapy to prevent NMIBC recurrence and progression,
yet BCG has a 30% failure rate, with various adverse effects leading to intolerance. Two critical needs exist: 1)
a risk stratification tool to identify patients at high risk of recurrence and progression for early and aggressive
treatment, and 2) a response prediction tool to identify patients who are unresponsive or intolerant to BCG for
other treatment options. Our goal is to develop and validate risk-stratification and BCG-response tools by
incorporating molecular signatures into the current pathological system for optimal clinical care of NMIBC.
Transcriptome analysis is powerful to identify genes, and importantly, to define cancer molecular subtypes
associated with different therapeutic and prognostic outcomes. This approach has been applied in bladder
cancer but primarily focused on MIBC. Research on NMIBC is an unmet need. Building on the Bladder Cancer
Epidemiology, Wellness, and Lifestyle Study (Be-Well), one of the largest prospective cohorts of NMIBC
patients, we propose to conduct a comprehensive transcriptomic analysis of NMIBC and examine the utility of
molecular subtypes with additional prognostic genes in predicting NMIBC treatment response and prognostic
outcomes. Our central hypothesis is that molecular signatures (i.e., molecular subtypes and/or other
genes) could unveil NMIBC heterogeneity and thus improve the current pathological classification
system for tailored NMIBC care. We will: Aim 1. Develop a risk stratification tool for NMIBC prognostic
outcomes by incorporating molecular subtypes, genes, clinicopathological and demographic factors. Primary
outcomes will be disease recurrence and progression, with survival explored. We will define molecular
subtypes and identify genes by NMIBC prognostic outcomes (1a), build risk prediction models in Be-Well
(n=928) (1b), validate molecular signatures and the risk-stratification tool in an independent validation cohort
(n=959) (1c), and explore the tool in sex and race specific groups in the pooled cohorts (1d). Aim 2. Develop a
response prediction tool for BCG outcomes by incorporating molecular subtypes, immune signatures, genes,
clinicopathological and demographic factors. Primary outcomes will be BCG unresponsive with BCG intolerant
explored. Given the high immunogenic nature of bladder cancer and BCG therapy, we will develop the BCG-
response prediction tool with further consideration of immune signatures in patients who received BCG in Be-
Well (n=426) and a validation cohort (n=691). We will explore characterization of molecular subtypes by sex,
race/ethnicity, and etiological risk factors. Clinical translation will be accelerated given the generation of
NMIBC-specific molecular signatures using NanoString in a large health care delivery system setting.
Publications
The Influence of Dietary Isothiocyanates on the Effectiveness of Mitomycin C and Bacillus Calmette-Guérin in Treating Nonmuscle-Invasive Bladder Cancer.
Authors: Kwan M.L.
, Wang Z.
, Haque R.
, Lee V.S.
, Roh J.M.
, Ergas I.J.
, Cannavale K.L.
, Pratt R.
, Goniewicz M.
, Loo R.K.
, et al.
.
Source: The Journal Of Urology, 2024-06-07 00:00:00.0; , p. 101097JU0000000000004070.
EPub date: 2024-06-07 00:00:00.0.
PMID: 38848543
Related Citations
Modifying Effects of Genetic Variations on the Association Between Dietary Isothiocyanate Exposure and Non-muscle Invasive Bladder Cancer Prognosis in the Be-Well Study.
Authors: Wang Z.
, Kwan M.L.
, Haque R.
, Singh P.K.
, Goniewicz M.
, Pratt R.
, Lee V.S.
, Roh J.M.
, Ergas I.J.
, Cannavale K.L.
, et al.
.
Source: Molecular Nutrition & Food Research, 2024-04-06 00:00:00.0; , p. e2400087.
EPub date: 2024-04-06 00:00:00.0.
PMID: 38581346
Related Citations