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Biomarkers in Urologic Cancer, An Issue of Urologic Clinics of North America, E-Book

Biomarkers in Urologic Cancer, An Issue of Urologic Clinics of North America, E-Book

Kevin R. Loughlin

(2016)

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Book Details

Abstract

The past decade has been marked by the acceleration of our understanding of the molecular biology of cancer. Simultaneously, there have been increasing exigencies to diagnose, treat and follow cancer patients more economically. Biomarkers represent the marriage of science and economics. Biomarkers offer the potential to increase the precision of diagnosis, prognosis, and surveillance of urological malignancies. This issue presents the cutting-edge advances of biomarker technology to urologic oncology.

Table of Contents

Section Title Page Action Price
Front Cover Cover
Biomarkers in Urologic Cancer\r i
Copyright \r ii
PROGRAM OBJECTIVE iii
TARGET AUDIENCE iii
LEARNING OBJECTIVES iii
ACCREDITATION iii
DISCLOSURE OF CONFLICTS OF INTEREST iii
UNAPPROVED/OFF-LABEL USE DISCLOSURE iii
TO ENROLL iv
METHOD OF PARTICIPATION iv
CME INQUIRIES/SPECIAL NEEDS iv
Contributors v
CONSULTING EDITOR v
EDITOR v
AUTHORS v
Contents ix
Foreword: Biomarkers in Urologic Cancer\r ix
Preface: Biomarkers in Urologic Cancer\r ix
The Prostate Health Index: Its Utility in Prostate Cancer Detection\r ix
New Genetic Markers for Prostate Cancer\r ix
Urinary Biomarkers for Prostate Cancer\r ix
4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening\r ix
Current Status of Urinary Biomarkers for Detection and Surveillance of Bladder Cancer\r x
Emerging Bladder Cancer Biomarkers and Targets of Therapy\r x
Pharmacogenomics: Biomarker-Directed Therapy for Bladder Cancer\r x
Diagnostic Biomarkers in Eosinophilic Renal Neoplasms\r x
Prognostic Biomarkers for Response to Vascular Endothelial Growth Factor–Targeted Therapy for Renal Cell Carcinoma\r xi
Prognostic Role of Cell Cycle and Proliferative Markers in Clear Cell Renal Cell Carcinoma\r xi
Current Clinical Applications of Testicular Cancer Biomarkers\r xi
MicroRNAs in Testicular Cancer Diagnosis and Prognosis\r xi
The Emerging Role and Promise of Biomarkers in Penile Cancer\r xii
UROLOGIC CLINICS OF NORTH AMERICA\r xiii
FORTHCOMING ISSUES xiii
May 2016 xiii
August 2016 xiii
November 2016 xiii
RECENT ISSUES xiii
November 2015 xiii
August 2015 xiii
May 2015 xiii
Foreword: Biomarkers in Urologic Cancer \r xv
Preface: Biomarkers in Urologic Cancer \r xvii
The Prostate Health Index 1
Key points 1
INTRODUCTION 1
PHI AS A PREDICTOR OF BIOPSY OUTCOME 2
PHI AS A COMPONENT OF MULTIVARIABLE RISK STRATIFICATION 3
PHI AS A PREDICTOR OF TREATMENT OUTCOME 3
COMPARISON OF PHI WITH OTHER PROSTATE CANCER TESTS 4
SUMMARY 5
REFERENCES 5
New Genetic Markers for Prostate Cancer 7
Key points 7
INTRODUCTION 7
PRINCIPLES OF DESIGN AND EVALUATION 8
Phases of Critical Evaluation 8
TESTS BEFORE DIAGNOSIS 8
URINARY-BASED GENE EXPRESSION ASSAYS 8
Prostate Cancer Antigen 3 8
Transmembrane Protease Serine 2:ERG 9
Urinary Exosomal Assays 9
TISSUE-BASED GENE EXPRESSION TESTS 9
ConfirmMDx (MDxHealth, Irvine, California) 9
PROLARIS (MYRIAD GENETICS INC, SALT LAKE CITY, UTAH) 10
At Initial Diagnosis: Prostate Biopsy Specimens 10
Oncotype DX Genomic Prostate Score (Genomic Health, Redwood City, California) 10
Supporting Data: Prostate Biopsy Specimens 11
DECIPHER (GENOMEDX, VANCOUVER, BRITISH COLUMBIA) 12
Following Definitive Treatment 12
SUMMARY 12
REFERENCES 13
Urinary Biomarkers for Prostate Cancer 17
Key points 17
INTRODUCTION 17
Urine as a Substrate 17
RNA-BASED MARKERS 18
Prostate Cancer Antigen 3 18
From bench to bedside 18
Repeat biopsy: diagnosis 19
The contemporary era 19
Initial biopsy: diagnosis and prognosis 20
Unique applications 20
Active surveillance 22
Prostate cancer antigen 3: summary 22
TMPRSS2:ERG 22
From bench to bedside 22
The contemporary era 23
Active surveillance 24
TMPRSS2:ERG summary 24
Other RNA-Based Markers 25
MicroRNA 25
Long noncoding RNA 25
DNA-BASED MARKERS 25
Cell-free DNA 25
Tumor-Specific Alterations 27
Genetic alterations 27
Epigenetic alterations 27
PROTEIN-BASED MARKERS 28
OTHER URINARY MARKERS 29
Metabolomics 29
Exosomes 30
The Microbiome 30
SUMMARY 31
REFERENCES 31
4-Kallikrein Test and Kallikrein Markers in Prostate Cancer Screening 39
Key points 39
INTRODUCTION 39
LIMITATIONS IN PROSTATE-SPECIFIC ANTIGEN–BASED SCREENING FOR PROSTATE CANCER 40
HUMAN KALLIKREINS 40
KALLIKREIN PANEL 40
Method for Evaluating the 4 Kallikrein Panel 41
FOUR KALLIKREIN STUDIES IN MEN BEFORE BIOPSY 41
Unscreened Men 41
Screened Men 41
FOUR KALLIKREIN STUDIES IN MEN WITH PRIOR NEGATIVE BIOPSY 43
SURGICAL PATHOLOGY PREDICTION 43
DEVELOPMENT OF THE 4K PROBABILITY SCORE 43
United States Prospective Validation 43
THE ECONOMIC IMPACT OF THE 4 KALLIKREIN PANEL AND 4KSCORE 44
SUMMARY 44
REFERENCES 44
Current Status of Urinary Biomarkers for Detection and Surveillance of Bladder Cancer 47
Key points 47
INTRODUCTION 47
MATERIAL AND METHOD 48
COMMERCIALLY AVAILABLE BIOMARKERS 48
Food and Drug Administration–Approved Biomarkers 48
Nuclear matrix protein 22 48
Bladder tumor antigen 49
ImmunoCyt/uCyt 49
UroVysion 50
Non–Food and Drug Administration–Approved Biomarkers 50
CxBladder 50
Survivin 51
Cytokeratin fragment 21.1 51
Bladder cancer rapid test 51
INVESTIGATIONAL BIOMARKERS 51
Protein-Based and Cell-Based Biomarkers 51
Apoptosis markers 51
Angiogenesis markers 52
Proliferation and invasion 52
Metabolomics 52
Gene-Based Biomarkers 53
Aurora A kinase 53
Fibroblast growth factor 3 receptor 53
Microsatellite/loss of heterozygosity detection 53
DNA methylation 53
MicroRNA 55
SUMMARY 55
REFERENCES 55
Emerging Bladder Cancer Biomarkers and Targets of Therapy 63
Key points 63
GENETIC AND MOLECULAR BIOMARKERS 63
GENOMICS OF BLADDER CANCER 63
BIOMARKERS AND PATHWAY TARGETS 65
Receptor Tyrosine Kinases and Cell-Cycle Markers 65
Epigenetic Markers 67
MONITORING/DETECTION METHODS 67
CLINICAL TRIALS 68
REFERENCES 72
Pharmacogenomics 77
Key points 77
INTRODUCTION AND AIMS 77
THE CLINICAL NEED AND PROMISE OF PREDICTIVE BIOMARKERS 78
EMERGING OPPORTUNITIES FOR PERSONALIZED THERAPEUTIC REGIMENS 78
INDIVIDUAL BIOMARKERS OF RESPONSE 79
DNA Repair Pathway Alterations: ERCC1 and ERCC2 79
TP53 79
PI3-kinase pathway 79
Receptor Tyrosine Kinases: FGFR3 and ERBB2 79
NEW APPROACHES TO THE CLASSIFICATION OF BLADDER CANCER 80
Immunotherapy: Promising New Horizons 81
CLINICAL TRIALS USING MOLECULARLY GUIDED THERAPY SELECTION 82
ACKNOWLEDGMENTS 83
REFERENCES 83
Diagnostic Biomarkers in Eosinophilic Renal Neoplasms 87
Key points 87
INTRODUCTION 87
Renal Oncocytoma Versus Chromophobe Renal Cell Carcinoma 88
Clear Cell Renal Cell Carcinoma with Eosinophilic Morphology Versus Translocation-Associated Renal Cell Carcinoma 89
Renal Cell Carcinoma, Unclassified (“Low-Grade Oncocytic Type”) Versus Oncocytoma and Chromophobe Renal Cell Carcinoma, Eos ... 91
Follicular Thyroid-like Carcinoma Versus Papillary Renal Cell Carcinoma and Renal Cell Carcinoma, Unclassified (“Low-Grade ... 91
Epithelioid Angiomyolipoma Versus High-Grade Renal Cell Carcinoma Unclassified, Renal Cell Carcinoma with Sarcomatoid Diffe ... 91
Papillary Neoplasms with Eosinophilic Features Versus Collecting Duct Carcinoma and Urothelial Carcinoma 92
Succinate Dehydrogenase Mutant Renal Cell Carcinoma 92
DISCUSSION 92
SUMMARY 93
REFERENCES 93
Prognostic Biomarkers for Response to Vascular Endothelial Growth Factor–Targeted Therapy for Renal Cell Carcinoma 95
Key points 95
INTRODUCTION 95
CIRCULATING/BLOOD-BASED BIOMARKERS 96
Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor–Related Proteins 96
Cytokine and Angiogenic Factors 96
Inflammatory Markers 97
TISSUE-BASED BIOMARKERS 98
Vascular Endothelial Growth Factor and Vascular Endothelial Growth Factor–Related Proteins 98
Carbonic Anhydrase-IX 99
von Hippel-Lindau Gene Functional Status 100
SINGLE-NUCLEOTIDE POLYMORPHISM AS BIOMARKERS FOR RESPONSE 100
FUTURE DIRECTIONS 100
SUMMARY 102
REFERENCES 102
Prognostic Role of Cell Cycle and Proliferative Markers in Clear Cell Renal Cell Carcinoma 105
Key points 105
INTRODUCTION 105
CELL CYCLE AND CELL PROLIFERATION 106
PROGNOSTIC VALUE OF CELL CYCLE AND PROLIFERATIVE MARKERS 106
p53 and TP53 106
p21 108
p27 108
Cyclin A 109
Cyclin B 109
Cyclin D 109
Cyclin E 111
pRB and RB1 112
Ki-67 112
MARKER COMBINATIONS 114
SUMMARY 114
REFERENCES 114
Current Clinical Applications of Testicular Cancer Biomarkers 119
Key points 119
INTRODUCTION 119
CLINICAL UTILITY OF TRADITIONAL SERUM TUMOR MARKERS 120
Screening Utility of Serum Tumor Markers 120
Diagnostic Utility of Serum Tumor Markers 120
Staging Utility of Serum Tumor Markers 121
Measurement of Response to Treatment by Serum Tumor Markers 121
Decline after Treatment of Metastatic Disease 121
AVAILABLE BIOMARKERS FOR TESTICULAR CANCER 122
FUTURE BIOMARKERS FOR TESTICULAR CANCER UNDER INVESTIGATION 123
REFERENCES 124
MicroRNAs in Testicular Cancer Diagnosis and Prognosis 127
Key points 127
INTRODUCTION 127
MOLECULAR ASPECTS OF MICRORNA BIOGENESIS 128
MICRORNAS IN TESTICULAR CANCER 128
MICRORNAS AS DIAGNOSTIC BIOMARKERS IN TESTICULAR CANCER 131
MICRORNAS, PROGNOSIS, AND CISPLATIN-BASED TREATMENT 132
REFERENCES 133
The Emerging Role and Promise of Biomarkers in Penile Cancer 135
Key points 135
INTRODUCTION 135
Epidemiology 135
Pathology 135
Management 135
PLASMATIC BIOMARKERS 136
Squamous Cell Carcinoma Antigen 136
C-Reactive Protein 137
PROLIFERATION ASSOCIATED BIOMARKERS 137
Ki-67 137
Proliferating Cell Nuclear Antigen 137
HUMAN PAPILLOMAVIRUS 138
Human Papillomavirus: a Risk Factor for Penile Cancer 138
Human Papillomavirus: Prognostic Marker for Penile Cancer 138
Prognostic marker for survival 138
Prognostic factors for lymph node metastasis 138
The Prognostic Significance of a Human Papillomavirus Marker: P16INK4a 138
P53 139
Is There a Link Between p53 and Human Papillomavirus Infection? 139
The Prognostic Role of p53 in Penile Cancer 139
CYTOGENETIC MARKERS 139
Genetic Imbalances 139
Epigenetic Modifications 140
SUMMARY/DISCUSSION 140
REFERENCES 140
Index 145