University Of Miami School Of Medicine
United States
MRI Imaging and Biomarkers for Early Detection of Aggressive Prostate Cancer
Oversampling and overdiagnosis of prostate cancer are significant management and cost issues that burden our health care system and the individual at risk with unnecessary biopsies and potential complications. The proposed studies will validate recent advances in quantitative prostate multiparametric MRI (mpMRI) techniques, blood biomarkers of aggressive prostate cancer and radiogenomics that relate to increased aggressive cancer risk by our group and collaborators. The overarching goal is to increase the negative predictive value (NPV) for significant prostate cancer and consequently reduce unnecessary biopsies. Central to the proposal are key collaborations between investigators from the Consortium for Imaging and Biomarkers (CIB), Early Detection Research Network (EDRN), and Jet Propulsion Laboratories (JPL). Novel automated techniques for quantitative analysis of mpMRI that identify prostate habitats at risk of harboring significant prostate cancer (Gleason score 3+4 and above or Grade Group (GG)2+) will be combined with improvements in mpMRI-ultrasound fusion biopsies. Our automated pixel-by-pixel 3D prostate habitat risk scoring (HRS) system is superior to the standard prostate lesion classification system, PIRADSv2, and is hypothesized to improve the Negative Predictive Value (NPV) for significant GG2+ cancers (Aim 1). Radiomics will be applied in Aim 1 to refine HRS in the University of Miami MDSelect protocol of 250 men (discovery=150; validation=100). Just as PIRADSv2 is suboptimal because it does not incorporate quantitative imaging information in risk stratification, models of risk based only on histopathologic grading ignore the underlying genomic determinants of outcome. We have shown that radiomics features are associated with underlying gene expression markers of adverse outcome. We propose in Aim 2 to apply newer criteria that incorporate Decipher® score with clinical-pathologic factors to improve the identification of aggressive prostate cancer. Radiomic features associated with these published criteria, termed the Spratt criteria, will improve the NPV for nonaggressive prostate cancer in the MDSelect cohort. We will also collaborate with investigators involved in the EDRN ID-430 clinical trial to test our models in a cohort (n=200) in a less rigorously controlled multi-institutional group with more variability in imaging techniques, vendors and machines. There is also opportunity to further improve risk classification through the analysis of blood-based markers (Aim 3) such as 4Kscore, circulating tumor cells (CTCs) and circulating cancer associated macrophage like (CAML) cells that are early biomarkers of aggressive cancer. The proposed work will test the incremental benefit of adding these serum-based biomarkers to improve the NPV models for significant prostate cancer.
Publications
- Hougen HY, Reis IM, Han S, Prakash NS, Thomas J, Stoyanova R, Castillo RP, Kryvenko ON, Ritch CR, Nahar B, Gonzalgo ML, Gaston SM, Abramowitz MC, Dal Pra A, Mahal BA, Pollack A, Parekh DJ, Punnen S. Evaluating 4Kscore's role in predicting progression on active surveillance for prostate cancer independently of clinical information and PIRADS score. Prostate cancer and prostatic diseases. 2025 Mar;28(1):180-186. Epub 2024 Sep 27. PMID: 39333697
- Ryan JT, Jin W, Porto JG, Mendiola D, Ajami T, Yu H, Mahal BA, Punnen S. Exploring prostate-specific antigen (PSA) Testing rates and screening disparities in the all of us dataset. Urologic oncology. 2025 Mar;43(3):194.e1-194.e8. Epub 2024 Nov 30. PMID: 39617681
- Ajami T, Yu H, Porto JG, Prakash NS, Williams A, Avda Y, Malpani A, Mendiola DF, Freitas PFS, Khandekar A, Swain S, Gaston S, Mahal B, Cortizas E, Szczotka Z, Gerard T, Kava B, Stoyanova R, Kryvenko ON, Castillo P, Ritch CR, Nahar B, Gonzalgo ML, Pollack A, Parekh DJ, Punnen S. Assessing the Molecular Heterogeneity of Prostate Cancer Biopsy Sampling: Insights from the MAST Trial. European urology focus. 2024 Dec 10. Epub 2024 Dec 10. PMID: 39665894
- Hougen HY, Sjoberg DD, Thomas J, Mahal BA, Vickers AJ, Punnen S. Adding a Coefficient for Race to the 4Kscore Improves Calibration for Black Men. The Journal of urology. 2024 Mar;211(3):392-399. Epub 2023 Dec 27. PMID: 38150383
- Freitas PFS, Khandekar A, Porto JG, Yu H, Williams AD, Avda Y, Malpani A, Ajami T, Mendiola DF, Soodana-Prakash N, Swain S, Gaston S, Kryvenko O, Davicioni E, Alshalalfa M, Hao Y, Mahal B, Cortizas E, Szczotka Z, Guerard T, Kava B, Stoyanova R, Ritch CR, Nahar B, Gonzalgo ML, Pollack A, Parekh DJ, Punnen S. Can Genomic Classifiers in Biopsy Cores With Grade Group 1 Cancer Predict Higher-Grade Disease Elsewhere in the Prostate? Results From the Prospective Miami Active Surveillance Trial. The Journal of urology. 2025 Jun 20: 101097JU0000000000004652. Epub 2025 Jun 20. PMID: 40540647
- Balagurunathan Y, Mitchell R, El Naqa I. Requirements and reliability of AI in the medical context. Physica medica : PM : an international journal devoted to the applications of physics to medicine and biology : official journal of the Italian Association of Biomedical Physics (AIFB). 2021 Mar;83:72-78. Epub 2021 Mar 13. PMID: 33721700
- Delgadillo R, Ford JC, Abramowitz MC, Dal Pra A, Pollack A, Stoyanova R. The role of radiomics in prostate cancer radiotherapy. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2020 Oct;196(10):900-912. Epub 2020 Aug 21. PMID: 32821953
- Punnen S, Stoyanova R, Kwon D, Reis IM, Soodana-Prakash N, Ritch CR, Nahar B, Gonzalgo ML, Kava B, Liu Y, Arora H, Gaston SM, Castillo Acosta RP, Pra AD, Abramowitz M, Kryvenko ON, Davicioni E, Pollack A, Parekh DJ. Heterogeneity in Genomic Risk Assessment from Tissue Based Prognostic Signatures Used in the Biopsy Setting and the Impact of Magnetic Resonance Imaging Targeted Biopsy. The Journal of urology. 2021 May;205(5):1344-1351. Epub 2020 Dec 24. PMID: 33356482
- Kimbel IM, Wallaengen V, Zacharaki EI, Breto AL, Algohary A, Carbohn S, Gaston SM, Soodana-Prakash N, Freitas PFS, Kryvenko ON, Castillo P, Abramowitz MC, Ritch CR, Nahar B, Gonzalgo ML, Parekh DJ, Pollack A, Punnen S, Stoyanova R. HRS Improves Active Surveillance for Prostate Cancer by Timely Identification of Progression. Academic radiology. 2025 Apr;32(4):2081-2089. Epub 2024 Dec 17. PMID: 39694787
- Thomas J, Atluri S, Zucker I, Reis I, Kwon D, Kim E, Tewari A, Patel V, Wagaskar V, Konety B, Kasraeian A, Czarniecki S, Thoreson G, Soodana-Prakash N, Ritch C, Nahar B, Gonzalgo M, Kava B, Parekh D, Punnen S. A multi-institutional study of 1,111 men with 4K score, multiparametric magnetic resonance imaging, and prostate biopsy. Urologic oncology. 2023 Oct;41(10):430.e9-430.e16. Epub 2023 Aug 4. PMID: 37544833
- Algohary A, Zacharaki EI, Breto AL, Alhusseini M, Wallaengen V, Xu IR, Gaston SM, Punnen S, Castillo P, Pattany PM, Kryvenko ON, Spieler B, Abramowitz MC, Pra AD, Ford JC, Pollack A, Stoyanova R. Uncovering prostate cancer aggressiveness signal in T2-weighted MRI through a three-reference tissues normalization technique. NMR in biomedicine. 2024 Mar;37(3):e5069. Epub 2023 Nov 21. PMID: 37990759
- Ku AT, Shankavaram U, Trostel SY, Zhang H, Sater HA, Harmon SA, Carrabba NV, Liu Y, Wood BJ, Pinto PA, Choyke PL, Stoyanova R, Davicioni E, Pollack A, Turkbey B, Sowalsky AG, Citrin DE. Radiogenomic profiling of prostate tumors prior to external beam radiotherapy converges on a transcriptomic signature of TGF-β activity driving tumor recurrence. medRxiv : the preprint server for health sciences. 2023 May 2. PMID: 37205576
- Stoyanova R, Zavala-Romero O, Kwon D, Breto AL, Xu IR, Algohary A, Alhusseini M, Gaston SM, Castillo P, Kryvenko ON, Davicioni E, Nahar B, Spieler B, Abramowitz MC, Dal Pra A, Parekh DJ, Punnen S, Pollack A. Clinical-Genomic Risk Group Classification of Suspicious Lesions on Prostate Multiparametric-MRI. Cancers. 2023 Oct 31;15. (21). PMID: 37958414
- Velez Torres JM, Briski LM, Martinez Duarte E, Sadow PM, Kerr DA, Kryvenko ON. Metastatic Clear Cell Renal Cell Carcinoma Involving the Thyroid Gland: A Clinicopathologic Study of 17 Patients. International journal of surgical pathology. 2022 Oct;30(7):743-752. Epub 2022 Mar 7. PMID: 35253524
- Zavala-Romero O, Breto AL, Xu IR, Chang YC, Gautney N, Dal Pra A, Abramowitz MC, Pollack A, Stoyanova R. Segmentation of prostate and prostate zones using deep learning : A multi-MRI vendor analysis. Strahlentherapie und Onkologie : Organ der Deutschen Rontgengesellschaft ... [et al]. 2020 Oct;196(10):932-942. Epub 2020 Mar 27. PMID: 32221622
- Ajami T, Han S, Porto JG, Kimbel I, Szczotka Z, Guerard T, VanderVeer-Harris N, Ledesma BR, Acosta PC, Kryvenko ON, Parekh DJ, Stoyanova R, Reis IM, Punnen S. Molecular and diffusion features for identification of clinically significant prostate cancer in PI-RADS 3 lesions. Urologic oncology. 2024 Nov;42(11):370.e9-370.e14. Epub 2024 Jul 8. PMID: 38971674