Complimentary genomic, pathologic, and artificial intelligence analysis on low-grade noninvasive bladder cancer to predict downstream recurrence.

Authors

null

Kyle M. Rose

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL

Kyle M. Rose , Aram Vosoughi , Gustavo Borjas , Heather L Huelster , Philippe E. Spiess , Anders E. Berglund , Wade J. Sexton , Anirudh Joshi , Nagi B. Kumar , Roger Li

Organizations

Department of Genitourinary Oncology, H. Lee Moffitt Cancer Center & Research Institute, Tampa, FL, H. Lee Moffitt Cancer Center, Tampa, FL, Moffitt Cancer Center, Tampa, FL, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, Valar Labs, Inc., Palo Alto, CA

Research Funding

No funding received
None.

Background: Low-grade noninvasive (LGTa) bladder cancer is a relatively quiescent but heterogenous malignancy, characterized by downstream recurrences requiring repeated transurethral resections and frequent surveillance. Investigations to elucidate drivers of recurrence have been sparse, but will help risk-stratify patients with LGTa and allow augmentation of follow up protocols. Methods: Patients with LGTa index tumors were stratified by those with no downstream recurrences (nonrecurrent) vs. those with later recurrences (recurrent). RNA sequencing identified differentially expressed genes (DEGs), deconvoluted for cell-type using xCell. Pathologic analysis was performed by a genitourinary pathologist, then a deep-learning artificial intelligence (AI) platform was leveraged to correlate recurrence risk and recurrence-free survival (RFS) based on deep-learning algorithm of segmented nuclei. Results: Thirty index bladder tumors/patients were identified, 18 (60%) of which had later recurrence (Table). There were 238 DEGs recognized, with recurrent tumors expressing signatures for epithelial mesenchymal transition, myogenesis, TNFα signaling via NFκB, and angiogenesis. Recurrent tumors also demonstrated a higher tissue micoenvironment, stroma, and cancer-associated fibroblast score. Pathologic TME analysis validated these findings, with recurrent tumors demonstrating a higher frequency of inverted growth pattern and a higher median stroma percentage. Finally, the AI-derived signature was predictive of recurrence and risk-stratified the cohort (HR= 5.43 [95% CI 1.1-26.76]) for predicting high vs. low risk of recurrence. Patients in the high risk group had a 87.5% recurrence rate while those in the low risk group had a 28.5% recurrence rate (p<0.01). Conclusions: Using a multi-disciplinary approach, we identified key signatures in recurrent LGTa bladder cancer. Characterization of these factors is a critical first step in the risk-stratification of LGTa tumors, and may allow risk-stratification of surveillance protocols and identification of possible targets for chemoprevention trials.

Clinicopathologic data and pathologic analysis of tumor microenvironment in patients with non-recurrent vs. recurrent LGTa cancer.
Demographics Non-recurrent LGTa
n= 12
Recurrent LGTa
n= 17
p-value
Age (years)*67.0 (63.5-72.5)68.0 (60.0-75.0)0.97
Gender
Female
Male

3
8

5
12
0.22
Smoking History
Yes
No

2
9

5
4
0.20
Tumor Size (mm)*12.0 (11.0-30.5)14.0 (12.0-19.0)0.53
No. Recurrences*
Months to Recurrence
4 (2-10)
9.0 (6.0-17.0)
NA
NA
Follow up (months)*71.0 (48.0-77.5)54.0 (49.0-62.0)0.86
Tumor Microenvironment Analysis§
Focal Cytologic and Architectural Atypia Suggestive of HG230.97
Inverted Growth Pattern150.04
Median Stroma %
20%50%<0.01

Disclaimer

This material on this page is ©2024 American Society of Clinical Oncology, all rights reserved. Licensing available upon request. For more information, please contact licensing@asco.org

Abstract Details

Meeting

2023 ASCO Genitourinary Cancers Symposium

Session Type

Poster Session

Session Title

Poster Session B: Prostate Cancer and Urothelial Carcinoma

Track

Urothelial Carcinoma,Prostate Cancer - Advanced

Sub Track

Translational Research, Tumor Biology, Biomarkers, and Pathology

Citation

J Clin Oncol 41, 2023 (suppl 6; abstr 553)

DOI

10.1200/JCO.2023.41.6_suppl.553

Abstract #

553

Poster Bd #

M16

Abstract Disclosures

Similar Abstracts

First Author: Benjamin Joshua Lerman

Abstract

2024 ASCO Annual Meeting

Impact of COVID-19 on post-treatment breast cancer surveillance and outcomes.

First Author: Erin Elizabeth Hahn