Molecular prognostic tests for prostate cancer
- Ashley Ross, MD, PhD
Ashley Ross, MD, PhD
- Associate Professor of Urology and Oncology
- 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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- Erho N, Crisan A, Vergara IA, et al. Discovery and validation of a prostate cancer genomic classifier that predicts early metastasis following radical prostatectomy. PLoS One 2013; 8:e66855.
- 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.
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- Karnes RJ, Choeurng V, Ross AE, et al. Validation of a Genomic Risk Classifier to Predict Prostate Cancer-specific Mortality in Men with Adverse Pathologic Features. Eur Urol 2017.
- Klein EA, Haddad Z, Yousefi K, et al. Decipher Genomic Classifier Measured on Prostate Biopsy Predicts Metastasis Risk. Urology 2016; 90:148.
- Nguyen PL, Martin NE, Choeurng V, et al. Utilization of biopsy-based genomic classifier to predict distant metastasis after definitive radiation and short-course ADT for intermediate and high-risk prostate cancer. Prostate Cancer Prostatic Dis 2017.
- 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.
- Dalela D, Santiago-Jiménez M, Yousefi K, et al. Genomic Classifier Augments the Role of Pathological Features in Identifying Optimal Candidates for Adjuvant Radiation Therapy in Patients With Prostate Cancer: Development and Internal Validation of a Multivariable Prognostic Model. J Clin Oncol 2017; :JCO2016699918.
- Ross AE, Den RB, Yousefi K, et al. Efficacy of post-operative radiation in a prostatectomy cohort adjusted for clinical and genomic risk. Prostate Cancer Prostatic Dis 2016; 19:277.
- Den RB, Yousefi K, Trabulsi EJ, et al. Genomic classifier identifies men with adverse pathology after radical prostatectomy who benefit from adjuvant radiation therapy. J Clin Oncol 2015; 33:944.
- 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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