Molecular prognostic tests for prostate cancer
- Ashley Ross, MD, PhD
Ashley Ross, MD, PhD
- Assistant Professor of Urology, Oncology, and Pathology
- Johns Hopkins Brady Urological Institute
- Anthony V D'Amico, MD, PhD
Anthony V D'Amico, MD, PhD
- Professor and Chief of Genitourinary Radiation Oncology
- Brigham and Women's Hospital
- Dana Farber Cancer Institute
- Harvard Medical School
- Stephen Freedland, MD
Stephen Freedland, MD
- Editor-in-Chief, Prostate Cancer and Prostatic Diseases
- Professor of Surgery (Urology)
- Director, Center for Integrated Research on Cancer and Lifestyle (CIRCL)
- Associate Director, Samuel Oschin Comprehensive Cancer Center
- Cedars Sinai Medical Center
- Section Editors
- Nicholas Vogelzang, MD
Nicholas Vogelzang, MD
- Section Editor — Prostate Cancer
- Professor of Medicine
- University of Nevada School of Medicine
- US Oncology Research
- Jerome P Richie, MD, FACS
Jerome P Richie, MD, FACS
- Section Editor — Cancer of the Urethra, Penis, and Ureter; Urologic Surgery; Prostate Cancer
- Elliott Carr Cutler Professor of Surgery
- Harvard Medical School
- W Robert Lee, MD, MS, MEd
W Robert Lee, MD, MS, MEd
- Section Editor — Prostate Cancer
- Professor of Radiation Oncology
- Duke University Medical Center
Prostate cancer represents the most common visceral malignancy in men. While prostate cancer remains a lethal disease (killing roughly 1 in every 36 American males), it represents a disease spectrum, particularly when localized disease is diagnosed, with up to half of men not needing immediate intervention. In addition to this, there are men with higher risk localized disease for whom the extent of treatment remains unclear (ie, surgical only, radiation only, or a combined modality approach that may include surgery, radiation, and/or androgen deprivation). (See "Initial approach to low- and very low-risk clinically localized prostate cancer" and "Initial management of regionally localized intermediate, high, and very high-risk prostate cancer".)
In order to better stratify and predict risk of prostate cancer progression, multiple clinicopathologic parameters have been investigated, and nomograms have been developed. While these are powerful tools, they have limitations. Advances over the last decade have dramatically increased both our understanding of prostate cancer biology and our ability to obtain molecular information from small amounts of prostate tissue. Along with these advances have come newly available and emerging clinical molecular tests, which promise to help determine prostate cancer prognosis and guide treatment decisions. (See "Prostate cancer: Risk stratification and choice of initial treatment".)
Current molecular tests that may better determine the aggressiveness of prostate cancer have been developed either based on general features of malignancy (namely proliferation indices) or based on molecular features that are more specific for prostate cancer (table 1). These tests include those that are based on immunohistochemistry (IHC) and those based on ribonucleic acid (RNA) expression. These tests, their possible clinical applications, and the literature supporting their use are discussed here.
TESTS BASED ON CELL PROLIFERATION
Tests based on cell proliferation include the evaluation by immunohistochemistry (IHC) of Ki-67, a nuclear protein that is associated with ribosomal ribonucleic acid (RNA) synthesis, and the cell cycle progression (CCP) score assessed by quantitative reverse transcription polymerase chain reaction (RT-PCR), which incorporates information from 31 cell cycle-related genes and 15 housekeeping genes.
Both Ki-67 IHC and the CCP score act as proxies for tumor proliferation. These tests have been employed in multiple retrospective cohorts, both with and without local treatment. Although they measure similar biological processes, they have not been directly compared; however, data for both tests appear similar.
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- Khor LY, Bae K, Paulus R, et al. MDM2 and Ki-67 predict for distant metastasis and mortality in men treated with radiotherapy and androgen deprivation for prostate cancer: RTOG 92-02. J Clin Oncol 2009; 27:3177.
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- Bishoff JT, Freedland SJ, Gerber L, et al. Prognostic utility of the cell cycle progression score generated from biopsy in men treated with prostatectomy. J Urol 2014; 192:409.
- Cooperberg MR, Simko JP, Cowan JE, et al. Validation of a cell-cycle progression gene panel to improve risk stratification in a contemporary prostatectomy cohort. J Clin Oncol 2013; 31:1428.
- Cuzick J, Berney DM, Fisher G, et al. Prognostic value of a cell cycle progression signature for prostate cancer death in a conservatively managed needle biopsy cohort. Br J Cancer 2012; 106:1095.
- Cuzick J, Swanson GP, Fisher G, et al. Prognostic value of an RNA expression signature derived from cell cycle proliferation genes in patients with prostate cancer: a retrospective study. Lancet Oncol 2011; 12:245.
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- Ding Z, Wu CJ, Chu GC, et al. SMAD4-dependent barrier constrains prostate cancer growth and metastatic progression. Nature 2011; 470:269.
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- Klein EA, Yousefi K, Haddad Z, et al. A genomic classifier improves prediction of metastatic disease within 5 years after surgery in node-negative high-risk prostate cancer patients managed by radical prostatectomy without adjuvant therapy. Eur Urol 2015; 67:778.
- Karnes RJ, Bergstralh EJ, Davicioni E, et al. Validation of a genomic classifier that predicts metastasis following radical prostatectomy in an at risk patient population. J Urol 2013; 190:2047.
- Ross AE, Johnson MH, Yousefi K, et al. Tissue-based Genomics Augments Post-prostatectomy Risk Stratification in a Natural History Cohort of Intermediate- and High-Risk Men. Eur Urol 2016; 69:157.
- Cooperberg MR, Davicioni E, Crisan A, et al. Combined value of validated clinical and genomic risk stratification tools for predicting prostate cancer mortality in a high-risk prostatectomy cohort. Eur Urol 2015; 67:326.
- Freedland SJ, Choeurng V, Howard L, et al. Utilization of a Genomic Classifier for Prediction of Metastasis Following Salvage Radiation Therapy after Radical Prostatectomy. Eur Urol 2016; 70:588.
- Zhao SG, Chang SL, Spratt DE, et al. Development and validation of a 24-gene predictor of response to postoperative radiotherapy in prostate cancer: a matched, retrospective analysis. Lancet Oncol 2016; 17:1612.
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- Klein EA, Cooperberg MR, Magi-Galluzzi C, et al. A 17-gene assay to predict prostate cancer aggressiveness in the context of Gleason grade heterogeneity, tumor multifocality, and biopsy undersampling. Eur Urol 2014; 66:550.
- Cullen J, Rosner IL, Brand TC, et al. A Biopsy-based 17-gene Genomic Prostate Score Predicts Recurrence After Radical Prostatectomy and Adverse Surgical Pathology in a Racially Diverse Population of Men with Clinically Low- and Intermediate-risk Prostate Cancer. Eur Urol 2015; 68:123.
- Brand TC, Zhang N, Crager MR, et al. Patient-specific Meta-analysis of 2 Clinical Validation Studies to Predict Pathologic Outcomes in Prostate Cancer Using the 17-Gene Genomic Prostate Score. Urology 2016; 89:69.
- Blume-Jensen P, Berman DM, Rimm DL, et al. Development and clinical validation of an in situ biopsy-based multimarker assay for risk stratification in prostate cancer. Clin Cancer Res 2015; 21:2591.