Table Of ContentCurrent Clinical Urology
Series Editor: Eric A. Klein
Fred Saad
Mario A. Eisenberger Editors
Management
of Castration
Resistant
Prostate Cancer
C C U
URRENT LINICAL ROLOGY
ERIC A. KLEIN, MD, SERIES EDITOR
PROFESSOR OF SURGERY
CLEVELAND CLINIC LERNER COLLEGE OF MEDICINE HEAD,
SECTION OF UROLOGIC ONCOLOGY
GLICKMAN UROLOGICAL AND KIDNEY INSTITUTE
CLEVELAND, OH
For further volumes:
http://www.springer.com/series/7635
Fred Saad (cid:129) Mario A. Eisenberger
Editors
Management
of Castration Resistant
Prostate Cancer
Editors
Fred Saad, MD, FRCS Mario A. Eisenberger, MD
Professor and Chief R.Dale Hughes Professor of Oncology
Division of Urology Professor of Urology
Director of Urologic Oncology The Sidney Kimmel Comprehensive
U of M Endowed Chair Cancer Center at Johns Hopkins
in Prostate Cancer The Johns Hopkins University
University of Montreal Hospital Center Baltimore , MD , USA
Montreal , QC , Canada
ISSN 2197-7194 ISSN 2197-7208 (electronic)
ISBN 978-1-4939-1175-2 ISBN 978-1-4939-1176-9 (eBook)
DOI 10.1007/978-1-4939-1176-9
Springer New York Heidelberg Dordrecht London
Library of Congress Control Number: 2014945340
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The opportunity to serve as co-editor of this book is the fruit of
over 25 years of working in the fi eld of prostate cancer. I would
like to thank the patients who have taught me how complex this
disease really is. As a clinical researcher I am especially
grateful to those patients who accepted to be included in
clinical trials. They have allowed me to witness some of the
most extraordinary results I have seen in my career. These
patients helped discover new treatment options that improve
and prolong the lives of others. I am also extremely grateful to
my clinical colleagues and co-researchers who have
contributed to improving our understanding and management
of prostate cancer. They have truly helped patients living with
prostate cancer but we still have much to do.
Finally, I thank and dedicate this book to my amazing wife
Rachel and the four beautiful children she has given me:
Genevieve, Julien, Veronique and Simon. Their love has made
my career and life complete.
Fred Saad
Over the past several years I had the privilege to conduct
multiple clinical trials in patients with prostate cancer, some
established new standards of care. This work is dedicated to all
patients (and their families) who entrusted their lives to me and
for those who so courageously agreed to participate in clinical
trials. Without them we would never be where we are now.
This book is also dedicated to my colleagues, clinical and
laboratory scientists, who have devoted their lives to improve
the outcomes of cancer patients.
To my wife Jannie (my soul mate), thank you for your support,
patience, and understanding during all these years. I am
grateful to the Universe for leading me through my current
path of life and for the precious gifts that I have been granted
and tried to cherish all these years. I pray and hope that one
day, my patients and I together, can witness the cure of this
devastating disease. To all I transmit what gives me strength
and hope in my daily life: “Never despair! Never! It is
forbidden to give up hope” (Rebbe Nachman of Breslov
1772–1810 ).1
Mario A. Eisenberger
1 T he Empty Chair; Finding Hope and Joy. Timeless Wisdom from a Hasidic Master, Rebbe
Nachman of Breslov (adapted by Mykoff M and the Breslov Research Institute). Jewish
Lights Publishing, Woodstock, Vermont, 2005, p. 110.
Pref ace
Prostate cancer is one of the most fascinating challenges we face in oncology.
Controversy about screening and over treatment has become the focus of
attention in almost every developed country in the western world. There has
been an explosion of new cases and an abundance of what many consider to
be “insignifi cant cancers” diagnosed. This has led large segments of the lay
population, as well as in the medical profession, to forget that prostate cancer
is still one of the top three causes of cancer-related death in the western world.
For almost all men who die of prostate cancer, castration-resistant disease
will be the cause of death. Until recently new therapeutic options that make a
difference were so limited that most men did not receive any treatment beyond
androgen deprivation therapy and supportive care. The last few years have
seen the fi eld go from rags to riches in terms of effective options and research
in the biology of CRPC is leading to exciting new therapeutic targets. Given
all the new data that is critical in understanding how we got here and where
the fi eld is going it was time to gather some of the most important players in
the fi eld and put it all together in an up-to-date book dedicated to castration-
resistant prostate cancer. The book reviews new data about the molecular
biology of CRPC as well as the staging procedures and prognostic factors that
defi ne CRPC. An in-depth review of proven therapeutic options is provided
that includes hormonal-based therapies, bone targeted therapies, immuno-
therapy, and chemotherapy. Combination therapy and novel targeted
approaches presently under investigation are also reviewed. Finally the book
concludes with an evidence-based management strategy based on present-
day knowledge and international guidelines.
I t was an honor to have had the opportunity to serve as the editors of this
book. With the incredible contributions by our colleagues who accepted to
write their respective chapters we certain that this book will serve as a useful
resource for physicians and researchers dealing with, and interested in, this
challenging state of prostate cancer. We also would like to dedicate this book
to all patients with prostate cancer and hope that this will contribute to further
improve their chances of survival and enhance their quality of life.
W e would like to thank to the team at Springer for realizing the importance
of the subject matter and a special thanks to Mr. Michael Griffi n for his
constant support in seeing this project become a reality.
Montreal, QC, Canada Fred Saad, MD, FRCS
Baltimore, MD, USA Mario A. Eisenberger, MD
vii
Contents
Part I Castrate-Resistant Prostate Cancer:
Clinical and Biological Considerations
1 Introduction—Castration Resistant Prostate Cancer:
A Rapidly Expanding Clinical State and a Model
for New Therapeutic Opportunities ............................................ 3
Mario A. Eisenberger and Fred Saad
2 Evolution of Clinical States and the Castration
Resistant Clinical Paradigm ......................................................... 9
Tian Zhang and Andrew J. Armstrong
3 Molecular Mechanisms of Prostate Cancer Progression
After Castration ............................................................................ 31
William G. Nelson and Kenneth J. Pienta
4 New Imaging Modalities ............................................................... 43
Steve Y. Cho, Seyed S. Dianat, and Katarzyna J. Macura
Part II Treatment: The Androgen Receptor Signaling Axis
Biology and Therapeutic Opportunities, Systemic
Chemotherapy, Immunotherapy, Bone Targeted
Approaches and Radiopharmaceuticals
5 Androgen Receptor Biology in Castration Resistant
Prostate Cancer ............................................................................. 67
Heather H. Cheng and Bruce Montgomery
6 The Androgen Receptor as a Therapeutic Target
for Castration-Resistant Prostate Cancer ................................... 77
Jarett L. Feldman, Dana Rathkopf, and Michael J. Morris
7 Approaches Targeting Androgen Synthesis
(CYP 17 Inhibitors) ....................................................................... 95
Adam Siegel and Charles J. Ryan
8 Cytotoxic Chemotherapy (Taxanes and Taxane
Combinations) ............................................................................... 107
Robert J. van Soest, Ellen S. de Morrée, Cora N. Sternberg,
and Ronald de Wit
ix
