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Grant Details

Grant Number: 5R01CA240991-02 Interpret this number
Primary Investigator: Morgan, Todd
Organization: University Of Michigan At Ann Arbor
Project Title: Determining the Clinical Impact of Gene Expression Testing in Localized Prostate Cancer
Fiscal Year: 2020


Abstract

The long-term goal of this project is to simultaneously decrease treatment-related morbidity from unnecessary over-treatment of men with localized prostate cancer (PCa) while curing more men by minimizing under- treatment of men with higher risk PCa. In this proposal we aim to determine if tissue based gene expression classifiers (GEC) can be utilized to improve both cancer control and quality of life (QOL) in men with localized PCa. This goal will be carried out through three specific aims. In Aim 1 we will develop a universal risk score that combines genetic, clinical, and pathologic variables in a manner that is agnostic to which of the three commercially available GEC tests used. This will be done through assembling a large cohort of men with targeted MRI/ultrasound fusion biopsies of the same prostate tumor focus and analyzing individual tumors with each of the three tests. We will then develop a conversion method aligning each GEC score with a new universal score, and we will apply this to a cohort of 1000 men with newly diagnosed prostate cancer followed in our statewide prospective registry. This data will be utilized to validate our recently developed clinical- genomic risk grouping system, broadening it to incorporate all GEC tests, and focusing it on appropriate stratification of favorable risk prostate cancer potentially suitable for active surveillance. We hypothesize that the universal integrated clinical-genomic risk groups will provide improved discrimination compared to standard clinical categories and will expand the pool of active surveillance-eligible patients. In Aim 2 we will conduct the first ever prospective randomized trial of the clinical utility and clinical impact of GEC testing in favorable risk localized prostate cancer, leveraging two statewide collaboratives containing over 60 urology and radiation oncology practices. Patients will be randomized to standard clinical risk stratification +/- GEC testing in order to determine the impact of testing on treatment decisions (active surveillance versus radical treatment), cancer control, and QOL. We hypothesize that GEC testing will decrease the use of primary therapy and increase QOL at 3 years, while maintaining rates of grade reclassification and biochemical recurrence at the same time point. Aim 3 seeks to determine the clinical impact of GEC testing on treatment failure and patient-reported QOL in men at high risk of recurrence post-prostatectomy. This aim leverages the recently accrued G-MINOR trial that randomized approximately 350 men at high risk of failure after prostatectomy to clinical risk stratification +/- GEC testing to assess decision making based on GEC testing. By extending the follow-up of this trial, we will determine how GEC testing impacts long-term tumor control and QOL. We hypothesize that GEC use in higher risk patients will provide more accurate risk stratification and targeted treatment decisions, leading to improved cancer control and QOL. This work has the potential to personalize treatment decision- making for PCa patients based on their tumor’s biology, allowing some men to avoid costly and toxic over- treatment while also decreasing the burden of recurrent disease from inappropriate under-treatment.



Publications

Comparing Patient-reported Functional Outcomes After Radical Prostatectomy in Historical and Contemporary Practice.
Authors: Singhal U. , Hollenbeck B.K. , Kaffenberger S.D. , Salami S.S. , George A.K. , Skolarus T.A. , Montgomery J.S. , Wittmann D.A. , Miller D.C. , Wei J.T. , et al. .
Source: The Journal Of Urology, 2023 Nov; 210(5), p. 771-777.
EPub date: 2023-08-11 00:00:00.0.
PMID: 37566643
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Genomic Classifier Performance in Intermediate-Risk Prostate Cancer: Results From NRG Oncology/RTOG 0126 Randomized Phase 3 Trial.
Authors: Spratt D.E. , Liu V.Y.T. , Michalski J. , Davicioni E. , Berlin A. , Simko J.P. , Efstathiou J.A. , Tran P.T. , Sandler H.M. , Hall W.A. , et al. .
Source: International Journal Of Radiation Oncology, Biology, Physics, 2023-10-01 00:00:00.0; 117(2), p. 370-377.
EPub date: 2023-05-02 00:00:00.0.
PMID: 37137444
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2022 Update on Prostate Cancer Epidemiology and Risk Factors-A Systematic Review.
Authors: Bergengren O. , Pekala K.R. , Matsoukas K. , Fainberg J. , Mungovan S.F. , Bratt O. , Bray F. , Brawley O. , Luckenbaugh A.N. , Mucci L. , et al. .
Source: European Urology, 2023 Aug; 84(2), p. 191-206.
EPub date: 2023-05-16 00:00:00.0.
PMID: 37202314
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Satisfaction With Clinician-Led Germline Genetic Counseling in Patients With Prostate Cancer.
Authors: Abusamra S.M. , Solorzano M.A. , Luke M. , Quarles J. , Jacobs M.F. , Das S. , Kasputis A. , Okoth L.A. , Patel M. , Seymore M. , et al. .
Source: The Journal Of Urology, 2022 11; 208(5), p. 1007-1017.
EPub date: 2022-08-05 00:00:00.0.
PMID: 35930793
Related Citations

Prostate Cancer With Peritoneal Carcinomatosis: A Robotic-assisted Radical Prostatectomy-based Case Series.
Authors: Goldenthal S.B. , Reimers M.A. , Singhal U. , Farha M. , Mehra R. , Piert M. , Tosoian J.J. , Modi P.K. , Curci N. , Peabody J. , et al. .
Source: Urology, 2022 Sep; 167, p. 171-178.
EPub date: 2022-04-25 00:00:00.0.
PMID: 35472327
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Trials in the Key of G: Building Level 1 Evidence on the Real-world Effectiveness of Prostate Biomarkers.
Authors: Okoth L.A. , Harris A.C. , Singhal U. , Cher M.L. , Spratt D.E. , Morgan T.M. .
Source: European Urology Focus, 2022 Jul; 8(4), p. 897-900.
EPub date: 2022-08-10 00:00:00.0.
PMID: 35963777
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Multigene Profiling of Circulating Tumor Cells (CTCs) for Prognostic Assessment in Treatment-Naïve Metastatic Hormone-Sensitive Prostate Cancer (mHSPC).
Authors: Reichert Z.R. , Kasputis T. , Nallandhighal S. , Abusamra S.M. , Kasputis A. , Haruray S. , Wang Y. , Williams S. , Singhal U. , Alva A. , et al. .
Source: International Journal Of Molecular Sciences, 2021-12-21 00:00:00.0; 23(1), .
EPub date: 2021-12-21 00:00:00.0.
PMID: 35008431
Related Citations

Impact of Decipher Biopsy testing on clinical outcomes in localized prostate cancer in a prospective statewide collaborative.
Authors: Vince R.A. , Jiang R. , Qi J. , Tosoian J.J. , Takele R. , Feng F.Y. , Linsell S. , Johnson A. , Shetty S. , Hurley P. , et al. .
Source: Prostate Cancer And Prostatic Diseases, 2021-07-20 00:00:00.0; , .
EPub date: 2021-07-20 00:00:00.0.
PMID: 34285350
Related Citations

Understanding the Barriers to Neoadjuvant Chemotherapy in Patients with Muscle Invasive Bladder Cancer: A Quality Improvement Initiative.
Authors: Andino J.J. , Sessine M. , Singhal U. , Reichert Z.R. , Wray D. , Shafer C. , Moore M. , Weizer A.Z. , Kaffenberger S.D. , Herrel L.A. , et al. .
Source: Urology Practice, 2021 Mar; 8(2), p. 217-225.
EPub date: 2020-10-14 00:00:00.0.
PMID: 33655019
Related Citations

Intermediate clinical endpoints for surrogacy in localised prostate cancer: an aggregate meta-analysis.
Authors: Gharzai L.A. , Jiang R. , Wallington D. , Jones G. , Birer S. , Jairath N. , Jaworski E.M. , McFarlane M.R. , Mahal B.A. , Nguyen P.L. , et al. .
Source: The Lancet. Oncology, 2021 03; 22(3), p. 402-410.
PMID: 33662287
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Development and Validation of a Clinical Prognostic Stage Group System for Nonmetastatic Prostate Cancer Using Disease-Specific Mortality Results From the International Staging Collaboration for Cancer of the Prostate.
Authors: Dess R.T. , Suresh K. , Zelefsky M.J. , Freedland S.J. , Mahal B.A. , Cooperberg M.R. , Davis B.J. , Horwitz E.M. , Terris M.K. , Amling C.L. , et al. .
Source: Jama Oncology, 2020-12-01 00:00:00.0; 6(12), p. 1912-1920.
PMID: 33090219
Related Citations

Wnt Signaling Drives Prostate Cancer Bone Metastatic Tropism and Invasion.
Authors: Wang Y. , Singhal U. , Qiao Y. , Kasputis T. , Chung J.S. , Zhao H. , Chammaa F. , Belardo J.A. , Roth T.M. , Zhang H. , et al. .
Source: Translational Oncology, 2020 Apr; 13(4), p. 100747.
EPub date: 2020-03-25 00:00:00.0.
PMID: 32217460
Related Citations

Transcriptomic Heterogeneity of Androgen Receptor Activity Defines a de novo low AR-Active Subclass in Treatment Naïve Primary Prostate Cancer.
Authors: Spratt D.E. , Alshalalfa M. , Fishbane N. , Weiner A.B. , Mehra R. , Mahal B.A. , Lehrer J. , Liu Y. , Zhao S.G. , Speers C. , et al. .
Source: Clinical Cancer Research : An Official Journal Of The American Association For Cancer Research, 2019-09-12 00:00:00.0; , .
EPub date: 2019-09-12 00:00:00.0.
PMID: 31515456
Related Citations

Clinical Utility of Gene Expression Classifiers in Men With Newly Diagnosed Prostate Cancer.
Authors: Hu J.C. , Tosoian J.J. , Qi J. , Kaye D. , Johnson A. , Linsell S. , Montie J.E. , Ghani K.R. , Miller D.C. , Wojno K. , et al. .
Source: Jco Precision Oncology, 2018; 2, .
EPub date: 2018-10-19 00:00:00.0.
PMID: 32832833
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