Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy

Goran Rac; Hiten D. Patel; Christopher James; Shalin Desai; Vincent M. Caruso; Daniel S. Fischer; Peter S. Lentz; Ceressa T. Ward; Brian C. Mazzarella; Kevin G. Phillips; Chirag Doshi; Vincent T. Bicocca; Trevor G. Levin; Alan J. Wolfe; Gopal N. Gupta

doi:10.1002/1878-0261.13530

Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy

Goran Rac^*, Hiten D. Patel, Christopher James, Shalin Desai, Vincent M. Caruso, Daniel S. Fischer, Peter S. Lentz, Ceressa T. Ward, Brian C. Mazzarella, Kevin G. Phillips, Chirag Doshi, Vincent T. Bicocca, Trevor G. Levin, Alan J. Wolfe, Gopal N. Gupta^*

^*Corresponding author for this work

Urology

Research output: Contribution to journal › Article › peer-review

1 Scopus citations

Abstract

Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

Original language	English (US)
Pages (from-to)	291-304
Number of pages	14
Journal	Molecular oncology
Volume	18
Issue number	2
DOIs	https://doi.org/10.1002/1878-0261.13530
State	Published - Feb 2024

Funding

VMC, DSF, PSL, CTW, BCM, KGP, VTB, and TGL report being employees and shareholders of Convergent Genomics. AJW discloses membership on the advisory boards of Urobiome Therapeutics and Pathnostics and funding from Pathnostics, VB Tech, the Craig H. Neilsen Foundation, and NIH. All other authors have no disclosures. We would like to acknowledge all the patients who participated in this study. We would like to acknowledge the American Association for Cancer Research and its financial and material support in the development of the AACR Project GENIE registry. Finally, we would like to acknowledge the TCGA Research Network: https://www.cancer.gov/tcga.

Keywords

Bacillus Calmette-Guérin
bladder cancer
genomics
intravesical instillation
personalized medicine
risk assessment

ASJC Scopus subject areas

Molecular Medicine
Oncology
Genetics
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1002/1878-0261.13530

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Rac, G., Patel, H. D., James, C., Desai, S., Caruso, V. M., Fischer, D. S., Lentz, P. S., Ward, C. T., Mazzarella, B. C., Phillips, K. G., Doshi, C., Bicocca, V. T., Levin, T. G., Wolfe, A. J., & Gupta, G. N. (2024). Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy. Molecular oncology, 18(2), 291-304. https://doi.org/10.1002/1878-0261.13530

@article{15ad329b003b40fcaac0c480ae978e57,

title = "Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy",

abstract = "Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp{\texttrademark} platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.",

keywords = "Bacillus Calmette-Gu{\'e}rin, bladder cancer, genomics, intravesical instillation, personalized medicine, risk assessment",

author = "Goran Rac and Patel, {Hiten D.} and Christopher James and Shalin Desai and Caruso, {Vincent M.} and Fischer, {Daniel S.} and Lentz, {Peter S.} and Ward, {Ceressa T.} and Mazzarella, {Brian C.} and Phillips, {Kevin G.} and Chirag Doshi and Bicocca, {Vincent T.} and Levin, {Trevor G.} and Wolfe, {Alan J.} and Gupta, {Gopal N.}",

note = "Publisher Copyright: {\textcopyright} 2023 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.",

year = "2024",

month = feb,

doi = "10.1002/1878-0261.13530",

language = "English (US)",

volume = "18",

pages = "291--304",

journal = "Molecular oncology",

issn = "1574-7891",

publisher = "John Wiley and Sons Ltd",

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Rac, G, Patel, HD, James, C, Desai, S, Caruso, VM, Fischer, DS, Lentz, PS, Ward, CT, Mazzarella, BC, Phillips, KG, Doshi, C, Bicocca, VT, Levin, TG, Wolfe, AJ & Gupta, GN 2024, 'Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy', Molecular oncology, vol. 18, no. 2, pp. 291-304. https://doi.org/10.1002/1878-0261.13530

TY - JOUR

T1 - Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy

AU - Rac, Goran

AU - Patel, Hiten D.

AU - James, Christopher

AU - Desai, Shalin

AU - Caruso, Vincent M.

AU - Fischer, Daniel S.

AU - Lentz, Peter S.

AU - Ward, Ceressa T.

AU - Mazzarella, Brian C.

AU - Phillips, Kevin G.

AU - Doshi, Chirag

AU - Bicocca, Vincent T.

AU - Levin, Trevor G.

AU - Wolfe, Alan J.

AU - Gupta, Gopal N.

PY - 2024/2

Y1 - 2024/2

N2 - Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

AB - Intravesical therapy (IVT) is the standard of care to decrease risk of recurrence and progression for high-grade nonmuscle-invasive bladder cancer. However, post-IVT recurrence remains common and the ability to risk-stratify patients before or after IVT is limited. In this prospectively designed and accrued cohort study, we examine the utility of urinary comprehensive genomic profiling (uCGP) for predicting recurrence risk following transurethral resection of bladder tumor (TURBT) and evaluating longitudinal IVT response. Urine was collected before and after IVT instillation and uCGP testing was done using the UroAmp™ platform. Baseline uCGP following TURBT identified patients with high (61%) and low (39%) recurrence risk. At 24 months, recurrence-free survival (RFS) was 100% for low-risk and 45% for high-risk patients with a hazard ratio (HR) of 9.3. Longitudinal uCGP classified patients as minimal residual disease (MRD) Negative, IVT Responder, or IVT Refractory with 24-month RFS of 100%, 50%, and 32%, respectively. Compared with MRD Negative patients, IVT Refractory patients had a HR of 10.5. Collectively, uCGP enables noninvasive risk assessment of patients following TURBT and induction IVT. uCGP could inform surveillance cystoscopy schedules and identify high-risk patients in need of additional therapy.

KW - Bacillus Calmette-Guérin

KW - bladder cancer

KW - genomics

KW - intravesical instillation

KW - personalized medicine

KW - risk assessment

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AN - SCOPUS:85173512113

SN - 1574-7891

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JO - Molecular oncology

JF - Molecular oncology

IS - 2

ER -

Urinary comprehensive genomic profiling predicts urothelial carcinoma recurrence and identifies responders to intravesical therapy

Abstract

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Keywords

ASJC Scopus subject areas

UN SDGs

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