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SEVENTH EDITION

PRINCIPLES ANDPRACTICE OFGYNECOLOGICONCOLOGY

Dennis S. Chi, MDDeputy ChiefHead of Ovarian Cancer SurgeryGynecology ServiceDepartment of SurgeryMemorial Sloan Kettering Cancer CenterNew York, New York

Andrew Berchuck, MDDirectorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyDirectorGynecologic Cancer ProgramDuke Cancer InstituteDuke University Medical CenterDurham, North Carolina

Don S. Dizon, MD, FACPClinical Co-DirectorGynecologic OncologyMassachusetts General Hospital Cancer CenterAssociate ProfessorHarvard Medical SchoolBoston, Massachusetts

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Catheryn Yashar, MDProfessorChief of Breast and Gynecologic ServicesMedical Director La JollaUniversity of California, San DiegoSan Diego, California

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Acquisitions Editor: Ryan ShawEditorial Coordinator: Dave MurphySenior Production Project Manager: Alicia JacksonDesign Coordinator: Holly McLaughlinManufacturing Coordinator: Beth WelshMarketing Manager: Rachel Mante LeungPrepress Vendor: S4Carlisle Publishing Services

Seventh edition

Copyright © 2017 Wolters Kluwer.

Copyright © 2013, 2009, 2005, 2001, 1996, 1992 by Lippincott Williams & Wilkins, A WoltersKluwer business. All rights reserved. This book is protected by copyright. No part of this bookmay be reproduced or transmitted in any form or by any means, including as photocopies orscanned-in or other electronic copies, or utilized by any information storage and retrieval systemwithout written permission from the copyright owner, except for brief quotations embodied incritical articles and reviews. Materials appearing in this book prepared by individuals as part oftheir official duties as U.S. government employees are not covered by the above-mentionedcopyright. To request permission, please contact Wolters Kluwer at Two Commerce Square,2001 Market Street, Philadelphia, PA 19103, via email at permissions@lww.com, or via ourwebsite at lww.com (products and services).

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Library of Congress Cataloging-in-Publication DataNames: Chi, Dennis S., editor. | Berchuck, Andrew, editor. | Dizon, Don S., editor. | Yashar, Catheryn M., editor.Title: Principles and practice of gynecologic oncology / [edited by] Dennis S. Chi, Andrew Berchuck, Don S. Dizon, Catheryn Yashar.Description: Seventh edition. | Philadelphia: Wolters Kluwer Health, [2017] | Includes bibliographical references and index.Identifiers: LCCN 2016048223 | ISBN 9781496380395Subjects: | MESH: Genital Neoplasms, FemaleClassification: LCC RC280.G5 | NLM WP 145 | DDC 616.99/465—dc23 LC record available athttps://lccn.loc.gov/2016048223

This work is provided “as is,” and the publisher disclaims any and all warranties, express orimplied, including any warranties as to accuracy, comprehensiveness, or currency of the contentof this work.

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This work is no substitute for individual patient assessment based upon health careprofessionals’ examination of each patient and consideration of, among other things, age, weight,gender, current or prior medical conditions, medication history, laboratory data, and other factorsunique to the patient. The publisher does not provide medical advice or guidance, and this workis merely a reference tool. Health care professionals, and not the publisher, are solely responsiblefor the use of this work, including all medical judgments, and for any resulting diagnosis andtreatments. Given continuous, rapid advances in medical science and health information, independentprofessional verification of medical diagnoses, indications, appropriate pharmaceutical selectionsand dosages, and treatment options should be made and health care professionals should consulta variety of sources. When prescribing medication, health care professionals are advised toconsult the product information sheet (the manufacturer’s package insert) accompanying eachdrug to verify, among other things, conditions of use, warnings, and side effects and identify anychanges in dosage schedule or contraindications, particularly if the medication to be administeredis new, infrequently used or has a narrow therapeutic range. To the maximum extent permittedunder applicable law, no responsibility is assumed by the publisher for any injury and/or damageto persons or property, as a matter of products liability, negligence law or otherwise, or from anyreference to or use by any person of this work.

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Dedication

his book is dedicated to our families: Hae-Young Chi and children Jessica, Stephanie, and Andrew Chi; AmyBerchuck and children Samuel, Jacob, and Benjamin Berchuck; Henry Stoll and children Isabelle, Harrison, andSophia Dizon-Stoll; Arnold Yashar and children William, Jacob, and Drew Yashar. Their patience, good humor,

encouragement, and love have inspired us throughout our careers. In this regard, they have each made significantcontributions to this book.

We would also like to express our gratitude to our own esteemed professors who guided and mentored us, and to all ofthe colleagues we have worked alongside, learned from, and taught over the years. The Gynecologic Oncology communitythat the readers of this book belong to is dedicated to the advancement of knowledge in the field and its application tooutstanding patient care. The considerable progress we have achieved together in the understanding, diagnosis, treatment,and prevention of these cancers is presented in this book. On behalf of the Gynecologic Oncology community, wededicate this edition of Principles and Practice of Gynecologic Oncology to the brave and courageous patients we allserve, and take inspiration in the oath we all share.

HIPPOCRATIC OATH

I swear to fulfill, to the best of my ability and judgment, this covenant:

I will respect the hard-won scientific gains of thosephysicians in whose steps I walk, and gladly share suchknowledge as is mine with those who are to follow.I will apply, for the benefit of the sick, all measures whichare required, avoiding those twin traps of overtreatment andtherapeutic nihilism.I will remember that there is art to medicine as well asscience, and that warmth, sympathy, and understanding mayoutweigh the surgeon's knife or the chemist’s drug.I will not be ashamed to say “I know not,” nor will I failto call in my colleagues when the skills of another areneeded for a patient’s recovery.I will respect the privacy of my patients, for their problemsare not disclosed to me that the world may know. Mostespecially must I tread with care in matters of life anddeath. Above all, I must not play at God.I will remember that I do not treat a fever chart, acancerous growth, but a sick human being, whose illness may

7

affect the person’s family and economic stability. Myresponsibility includes these related problems, if I am tocare adequately for the sick.I will prevent disease whenever I can, for prevention ispreferable to cure.I will remember that I remain a member of society, withspecial obligations to all my fellow human beings, thosesound of mind and body as well as the infirm.If I do not violate this oath, may I enjoy life and art,respected while I live and remembered with affectionthereafter. May I always act so as to preserve the finesttraditions of my calling and may I long experience the joy ofhealing those who seek my help.

8

International Editorial Board

Ali Ayhan, PhDProfessor and Chairman

Department of Gynecologic OncologyBaskent University School of Medicine

Ankara, Turkey

Uziel Beller, MDProfessor and ChairmanDepartment of Gynecology

Shaare Zedek Medical CenterThe Hebrew University of Jerusalem

Jerusalem, Israel

Prof. Adriana Bermudez, MD, PhDChair, Gynecologic Oncology UnitBuenos Aires University Hospital

Buenos Aires, Argentina

Dr. Jorge A. Brañes, MDProfesor Asociado

División de Obsteticia y GinecologíaFacultad de Medicina

Pontificia Universidad Católica de ChileSantiago, Chile

Luis M. Chiva, MD, PhDHead of Department of Gynecology OncologyPresident of the Educational Committee

Departments of Gynecologic and Medical OncologyThe University of Texas MD Anderson Cancer Center

Madrid, SpainAdjunct Professor of University of Texas

Houston, Texas

Dr. Carien L. Creutzberg, MDProfessor of Radiation OncologyDepartment of Radiation OncologyLeiden University Medical Centre

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Leiden, The Netherlands

Lynette Denny, MBChB, MMEDm, PhD, FCOG (SA)Professor and Head of Obstetrics and GynaecologyUniversity of Cape Town/Groote Schuur Hospital

Cape Town, South Africa

Gustavo Ferraris, MD, PhDAcademic Director

Radiation Oncology SpecialtyCatholic University of Córdoba

Medical DirectorDepartment of Radiation Therapy

Centro Médico Dean FunesCórdoba, Argentina

Michael L. Friedlander, PhD, FRACPConjoint Professor of Medicine

Department of MedicineUniversity of New South Wales

Sydney, Australia

Keiichi Fujiwara, MD, PhDProfessor and DirectorGynecologic Oncology

Saitama Medical University International Medical CenterHidaka-City, Saitama, Japan

Dr. Paweł Knapp, MD, PhDProfessor

Department of Gynaecology and Gynaecologic OncologyMedical University of Bialystok

Bialystok, Poland

Alexandra Leary, MD, PhDMedical OncologistGynecology Unit

Lead, Gynecology Translational Research LaboratoryGustave Roussy Cancer Centre

Villejuif, France

Helen MacKay, MBChB, BSc, MRCP, MDHead, Division of Medical Oncology & Hematology

Sunnybrook Odette Cancer CentreAssociate Professor

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Faculty of MedicineUniversity of Toronto

Toronto, Canada

Angelo Maggioni, MDDirector, Division of Gynecologic Oncology

European Institute of OncologyMilan, Italy

Umesh Mahantshetty, MDProfessor

Radiation OncologyTata Memorial Hospital

Mumbai, Maharashtra, India

Fernando Cotait Maluf, MDMember of the Steering Committee

Oncology CenterHospital Israelita Albert Einstein

Medical Oncology DirectorCentro Oncológico Antonio Ermírio de Moraes

Beneficência Portuguesa de São PauloSão Paulo, Brazil

Sang-Yoon Park, MD, PhDPresident, Korean Society of Peritoneal Surface Malignancies

Doctor/Principal Scientist Center for Uterine CancerNational Cancer Center

Republic of Korea

Prof. Denis Querleu, MDPresident-elect, European Society of Gynaecologic Oncology

Institut Bergonié Cancer CenterBordeaux, France

Maureen Trudeau, MD, FRCPCMedical Oncologist

Division of Medical Oncology & Hematology Sunnybrook Health Sciences Centre Professor

Faculty of MedicineUniversity of Toronto

Toronto, Canada

Xiaohua Wu, MD, PhDDirector and Professor

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Department of Gynecologic OncologyFudan University Shanghai Cancer Center

Shanghai, China

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Contributors

Fadi W. Abdul-Karim, MD, MEdDepartment of PathologyVice Chair of EducationRobert J. Tomisch Pathology and Laboratory Medicine InstituteProfessor of PathologyCleveland Clinic, Lerner College of MedicineCleveland, Ohio

Sunil J. Advani, MDAssociate ProfessorDepartment of Radiation Medicine and Applied SciencesUniversity of California, San DiegoLa Jolla, California

Ebtesam Ahmed, PharmD, MSAssociate Clinical ProfessorClinical Health ProfessionsSt. John UniversityQueens, New YorkDirector Pharmacy InternshipMJHS Institute for Innovation in Palliative CareNew York, New York

David S. Alberts, MDRegents Professor and Director EmeritusUniversity of Arizona Cancer CenterUniversity of ArizonaTucson, Arizona

Donald Armstrong, MDProfessor EmeritusMemorial Sloan Kettering Cancer CenterNew York, New York

Meena Bedi, MDAssistant Professor Department of Radiation OncologyMedical College of Wisconsin

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Milwaukee, Wisconsin

Andrew Berchuck, MDDirectorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyDirectorGynecologic Cancer ProgramDuke Cancer InstituteDuke University Medical CenterDurham, North Carolina

Sushil Beriwal, MDAssociate ProfessorUniversity of Pittsburgh Cancer InstituteDepartment of Radiation OncologyMagee-Womens Hospital of UPMCPittsburgh, Pennsylvania

Leslie Blackhall, MDAssociate Professor of Internal MedicineDivision of General Medicine, Geriatrics and Palliative CareDepartment of MedicinePalliative Care ClinicCharlottesville, Virginia

Michael A. Bookman, MDDirectorGynecologic Oncology ResearchUS Oncology and Arizona OncologyTucson, Arizona

David D. L. Bowtell, BVSc, PhDHeadCancer Genetics and Genomics and Senior Principal Research FellowResearch DepartmentPeter MacCallum Cancer Centre and Garvan Institute of Medical ResearchVictoria (Peter Mac) and NSW (Garvan), Australia

Mark F. Brady, PhDDirector of Statistics, GOG SDCGOG Statistical and Data CenterResearch ProfessorDepartment of BiostatisticsRoswell Park Cancer Institute

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Buffalo, New York

Donal J. Brennan, MB, MRCPI, MRCOG, PhDAssistant MasterDepartment of Obstetrics and GynecologyRotunda HospitalDublin, Ireland

Louise A. Brinton, PhDChiefHormonal and Reproductive EpidemiologyDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteNational Institutes of HealthBethesda, Maryland

Robert E. Bristow, MD, MBA Professor and ChairDepartment of Obstetrics and GynecologyUniversity of CaliforniaIrvine, California

Jubilee Brown, MDProfessor and Associate DirectorDepartment of Gynecologic OncologyLevine Cancer InstituteCarolinas HealthCare SystemCharlotte, North Carolina

James J. Burke II, MDThe Donald G. Gallup Scholar of Gynecologic OncologyThe Curtis and Elizabeth Anderson Cancer InstituteMemorial University Medical Center Associate Professor and DirectorDepartment of Gynecologic OncologyMercer University School of Medicine, Savannah CampusSavannah, Georgia

Hilary Calvert, MD, FRCPEmeritus Professor of Cancer TherapeuticsUCL Cancer InstituteResearch Department of OncologyFaculty of Medical Sciences London, England

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Susana M. Campos, MS, MD, MPHAssistant Professor of Medicine Medical OncologyHarvard Medical SchoolDana-Farber Cancer InstituteBoston, Massachusetts

Dennis S. Chi, MDDeputy ChiefHead of Ovarian Cancer SurgeryGynecology ServiceDepartment of SurgeryMemorial Sloan Kettering Cancer CenterNew York, New York

David Cibula, MD, PhDGynecologic Oncology Center Department of Obstetrics and Gynecology First Faculty of Medicine Charles University in Prague General University Hospital in Prague Prague, Czech Republic

David E. Cohn, MDStuart M. Sloan and Larry J. Copeland ChairDirectorDivision of Gynecologic OncologyProfessorDepartment of Obstetrics and GynecologyColumbus, Ohio

Mary B. Daly, MD, PhDChairDepartment of Clinical GeneticsFox Chase Cancer CenterPhiladelphia, Pennsylvania

Robert Debernardo, MDDirector of Minimally Invasive SurgeryGynecologic Oncology DivisionDepartment of Obstetrics and Gynecology and Women’s Health InstituteCleveland Clinic Cleveland, Ohio

Marcela G. del Carmen, MD

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ProfessorDivision of Gynecologic OncologyHarvard Medical SchoolBoston, Massachusetts

Don S. Dizon, MD, FACPClinical Co-DirectorGynecologic OncologyMassachusetts General Hospital Cancer CenterAssociate ProfessorHarvard Medical SchoolBoston, Massachusetts

Sean C. Dowdy, MD, FACS Professor and ChairDivision of Gynecologic Surgery Co-Leader, Women’s Cancer Program Mayo Clinic College of Medicine Rochester, Minnesota

Linda R. Duska, MD, MPHProfessorDepartment of Obstetrics and GynecologyFellowship DirectorDivision of Gynecologic OncologyAssociate Dean for Clinical Research University of Virginia School of Medicine Charlottesville, Virginia

David A. Edmonson, MD, FACSAssistant ProfessorDepartment of General SurgeryDepartment of Obstetrics and GynecologyDirectorLymphedema Program, PWOThe Warren Alpert Medical School of Brown UniversityProgram in Women’s OncologyWomen and Infants’ HospitalProvidence, Rhode Island

Mark H. Einstein, MD, MSProfessor and ChairDepartment of Obstetrics, Gynecology, and Women’s HealthRutgers New Jersey Medical SchoolNewark, New Jersey

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Robert E. Emerson, MDAssociate ProfessorDepartment of Pathology and Laboratory MedicineIndiana University School of MedicineIndianapolis, Indiana

Beth A. Erickson, MDProfessorDepartment of Radiation OncologyMedical College of WisconsinMilwaukee, Wisconsin

Britt K. Erickson, MD Assistant ProfessorGynecologic OncologistDepartment of Obstetrics and GynecologyDivision of Gynecologic Oncology University of Minnesota Minneapolis, Minnesota

Dariush Etemadmoghadam, PhDSenior Research OfficerDepartment of ResearchPeter MacCallum Cancer CentreVictoria, Australia

Amanda N. Fader, MDAssociate Professor and DirectorThe Kelly Gynecologic Oncology ServiceBaltimore, Maryland

Virginia L. Filiaci, PhDAssociate DirectorBiostatistics and Science GOG and NRG Oncology-Buffalo Statistics and Data Management Centers Roswell Park Cancer InstituteBuffalo, New York

Gini F. Fleming, MDProfessor of MedicineDirectorMedical Oncology Breast Program Medical Oncology DirectorGynecologic OncologyThe University of Chicago Medicine

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Chicago, Illinois

Silvia Franceschi, MDGroup Head, Special AdvisorInfections and Cancer Epidemiology GroupInternational Agency for Research on CancerLyon, France

Stéphanie L. Gaillard, MD, PhDAssistant ProfessorDepartment of Medicine/Division of Medical OncologyDuke University Medical CenterDurham, North Carolina

Aleksandra Gentry-Maharaj, PhDSenior Research AssociateGynecological Cancer Research CentreDepartment of Women’s CancerInstitute for Women’s HealthFaculty of Population Health SciencesUCLLondon, England

David M. Gershenson, MDProfessorDepartment of Gynecologic Oncology and Reproductive MedicineThe University of Texas MD Anderson Cancer CenterHouston, Texas

Charlie Gourley, BSc, MB ChB, PhD, FRCPProfessor of Medical OncologyNicola Murray Ovarian Cancer Research CentreEdinburgh Cancer Research UK CentreMRC IGMMThe University of EdinburghHonorary Consultant in Medical OncologyEdinburgh Cancer CentreWestern General HospitalUnited Kingdom

Laura J. Havrilesky, MD, MHScProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyDuke University Medical Center

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Durham, North Carolina

Jaroslaw T. Hepel, MD, FACROAssistant ProfessorDepartment of Radiation OncologyThe Warren Alpert School of Medicine at Brown UniversityRhode Island HospitalProvidence, Rhode Island

Warner K. Huh, MDProfessor and Division DirectorMargaret Cameron Spain Endowed Chair in Obstetrics/GynecologyDivision of Gynecologic OncologyUniversity of Alabama at BirminghamBirmingham, Alabama

Elizabeth L. Jewell, MDAssociate ProfessorDepartment of Obstetrics and GynecologyWeill Cornell Medical CollegeAssociate Attending SurgeonDepartment of SurgeryMemorial Sloan Kettering Cancer CenterNew York, New York

Josephine Kang, MD, PhDAssistant Professor of Clinical Radiation OncologyDepartment of Radiation OncologyNew York Presbyterian/Weill Cornell Medical CollegeNew York, New York

Noah D. Kauff, MDDirectorClinical Cancer GeneticsDuke Cancer InstituteDuke University Health SystemDurham, North Carolina

Hanan I. Khalil, MDAssistant ProfessorDepartment of Diagnostic ImagingThe Warren Alpert Medical School of Brown University Rhode Island Medical ImagingEast Providence, Rhode Island

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Elise C. Kohn, MD, CAPT (Ret.) USPHSHeadGynecologic Cancer TherapeuticsGastroenteropancreatic Neuroendocrine Cancer TherapeuticsLeadNCTN Core Correlative Science CommitteeClinical Investigations BranchCancer Therapy Evaluation ProgramNational Cancer Institute Attending PhysicianWomen’s Malignancies BranchMedical Oncology ProgramCenter for Cancer ResearchNational Cancer InstituteBethesda, Maryland

Shalini L. Kulasingam, MPH, PhDAssociate ProfessorSchool of Public HealthDivision of Epidemiology and Community HealthUniversity of Minnesota, Twin CitiesMinneapolis, Minnesota

Charles A. Kunos, MD, PhDAssociate ProfessorDepartment of Pharmaceutical SciencesNortheast Ohio Medical CenterRootstown, Ohio

Eric Leblanc, MDHeadDepartment of Gynecological Oncology Centre Oscar LambretLille, France

Larissa J. Lee, MDAssistant ProfessorRadiation OncologyBrigham and Women’s HospitalDana-Farber Cancer InstituteBoston, Massachusetts

Leslie K. Lee, MDStaff RadiologistDepartment of Radiology

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Brigham and Women’s HospitalInstructor of RadiologyHarvard Medical SchoolBoston, Massachusetts

Susanna I. Lee, MD, PhDAssociate ProfessorDepartment of RadiologyHarvard Medical SchoolStaff RadiologistDepartment of RadiologyMassachusetts General HospitalBoston, Massachusetts

Carolyn Lefkowits, MD, MPH, MSAssistant ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyUniversity of Colorado School of MedicineDenver, Colorado

Robert D. Legare, MDAssociate Professor of Obstetrics and Gynecology (Clinical)Associate Professor of Medicine (Clinical)Department of Obstetrics and GynecologyAlpert Medical SchoolBrown UniversityProvidence, Rhode Island

Mario M. Leitao Jr, MDAssociate ProfessorDepartment of Obstetrics and GynecologyWeill Cornell Medical CollegeAssociate Attending SurgeonGynecology ServiceDepartment of SurgeryMemorial Sloan Kettering Cancer CenterNew York, New York

Ernst Lengyel, MD, PhDChairmanDepartment of Obstetrics and Gynecology Arthur L. and Lee G. Herbst Professor of Obstetrics and Gynecology University of Chicago MedicineChicago, Illinois

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Pauline Lesage, MD, LLMPhysician Educator MJHS Institute for Innovation in Palliative CareNew York, New YorkAssociate Professor Department of Family and Social MedicineAlbert Einstein College of Medicine Bronx, New York

Douglas A. Levine, MDDirectorGynecologic Oncology, Laura and Isaac Perlmutter Cancer CenterHeadGynecology Research LaboratoryProfessorDivision of Gynecologic Oncology Department of Obstetrics and GynecologyNYU Langone Medical CenterNew York, New York

Stephanie Lheureux, MD, PhDAssociate ProfessorFaculty of MedicineUniversity of TorontoStaffDepartment of Medical Oncology and HematologyPrincess Margaret Cancer CenterToronto, Canada

Maria Lluria-Prevatt, PhDResearch AdministratorUniversity of Arizona Cancer CenterUniversity of ArizonaTucson, Arizona

Karen H. Lu, MDJ. Taylor Wharton Distinguished Chair in Gynecologic OncologyDepartment of Gynecologic Oncology and Reproductive Medicine Division of SurgeryChairDepartment of Gynecologic Oncology and Reproductive MedicineDivision of SurgeryThe University of Texas MD Anderson Cancer Center Houston, Texas

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John R. Lurain, MDMarcia Stenn Professor of Gynecologic OncologyDepartment of Obstetrics and GynecologyFineberg School of MedicineNorthwestern UniversityChicago, Illinois

Heather MacNew, MDAssistant Professor Surgical Critical Care and Acute Care SurgeryMercer University School of MedicineMemorial University Medical CenterSavannah, Georgia

Gina M. Mantia-Smaldone, MDAssistant ProfessorDepartment of Surgical OncologyDivision of Gynecologic OncologyFox Chase Cancer CenterPhiladelphia, Pennsylvania

Daniela Matei, MDProfessorDiana Princess of Wales Professor in Cancer ResearchNorthwestern University Feinberg School of MedicineChicago, Illinois

Shaunagh McDermott, MB, BCh, BAOInstructorHarvard Medical SchoolRadiologistDepartment of Thoracic ImagingMassachusetts General HospitalBoston, Massachusetts

D. Scott McMeekin†, MDVirginia Cade ChairCancer Development TherapeuticsDeputy Director for Clinical ResearchSection Chief, Gynecologic OncologyUniversity of OklahomaOklahoma City, Oklahoma

Usha Menon, MD (RES), FRCOGProfessor of Gynaecological Cancer

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Department of Women’s CancerUCL Institute for Women’s HealthLondon, United Kingdom

Jeffrey C. Miecznikowski, PhDAssociate ProfessorDepartment of BiostatisticsSUNY University at BuffaloBuffalo, New York

Bradley J. Monk, MD, FACOG, FACSProfessorDirectorDivision of Gynecologic OncologyVice ChairDepartment of Obstetrics and GynecologyUniversity of Arizona Cancer Center-PhoenixCreighton University School of Medicine atDignity Health St. Joseph’s Hospital and Medical CenterPhoenix, Arizona

John W. Moroney, MDAssociate ProfessorDivision of Gynecologic OncologyDepartment of Obstetrics and GynecologyUniversity of ChicagoChicago, Illinois

Firas Mourtada, PhD, DABR, FAAPMAdjunct Associate ProfessorDepartment of Radiation OncologyThomas Jefferson UniversityPhiladelphia, PennsylvaniaChief of Clinical PhysicsDepartment of Radiation OncologyChristiana Health Care SystemsNewark, DelawareAssociate ProfessorDepartment of Radiation PhysicsThe University of Texas MD Anderson Cancer CenterHouston, Texas

Andreas Obermair, MD, FRANZCOG, CGODirector of ResearchQueensland Centre for Gynecological Cancer

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Herston, Brisbane, Australia

Roisin O’Cearbhaill, MB, BCh, BAOAssistant ProfessorDepartment of MedicineWeill Cornell Medical CollegeAssistant Attending PhysicianGynecologic Medical Oncology ServiceDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New York

Kunle Odunsi, MD, PhDCancer Center Deputy DirectorThe M. Steven Piver Professor and ChairDepartment of Gynecologic OncologyExecutive DirectorCenter for ImmunotherapyRoswell Park Cancer InstituteBuffalo, New York

Amit M. Oza, BSc, MD, MBBS, FRCPProfessorFaculty of MedicineUniversity of TorontoCo-DirectorDrug Development ProgramPrincess Margaret Cancer CenterToronto, Canada

Sonali V. Pandya, MD, FACSBreast SurgeonDepartment of Surgery - Clinical Instructor at Brown UniversityWomen and Infants’ HospitalProvidence, Rhode Island

Emily Penick, MDCaptain, Medical Corps, U.S. ArmyDivision of Gynecologic OncologyWalter Reed National Military Medical CenterClinical Assistant ProfessorUniformed Services University of the Health SciencesBethesda, Maryland

Jacobus Pfisterer, MD, PhD

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DirectorGynecologic Oncology CenterChairmanAGO Study GroupPast Chair/Member of the Executive CommitteeGynecologic Cancer Intergroup GCIGKiel, Germany

Russell K. Portenoy, MDProfessor Department of NeurologyAlbert Einstein College of MedicineExecutive DirectorMJHS Institute for Innovation in Palliative CareNew York, New York

Scott C. Purinton, MD, PhDAssistant ProfessorDepartment of Obstetrics and GynecologyMercer University School of MedicineAssistant ProfessorAnderson Cancer Institute Surgical AssociatesAnderson Cancer InstituteMemorial University Medical CenterSavannah, Georgia

Denis Querleu, MDPresident-electEuropean Society of Gynaecologic OncologyInstitut Bergonié Cancer CenterBordeaux, France

Tina Rizack, MD, MPHMedical Oncology/HematologyProgram in Women’s OncologyWomen & Infants HospitalAssistant Professor (Clinical) of Medicine and Obstetrics and GynecologyAlpert Medical School of Brown UniversityProvidence, Rhode Island

Kenneth Rolston, MD, FACPInternist and Professor of MedicineDepartment of Infectious Diseases, Infection Control and Employee HealthDivision of Internal MedicineThe University of Texas MD Anderson Cancer Center

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Houston, Texas

Paul J. Sabbatini, MDAttending PhysicianGynecologic Medical Oncology ServiceDeputy Physician-in-Chief for Clinical ResearchMemorial Sloan Kettering Cancer CenterNew York, New York

Amar Safdar, MDAssociate Professor of MedicineDepartment of Infectious Diseases and ImmunologyNYU School of MedicineDirectorTransplant Infectious DiseasesDepartment of MedicineNYU Langone Medical CenterNew York, New York

Vikrant V. Sahasrabuddhe, D. PHProgram DirectorDivision of Cancer PreventionNational Cancer InstituteBethesda, Maryland

Mark Schattner, MDProfessor of Clinical MedicineDepartment of MedicineWeill Cornell Medical CollegeAttending PhysicianGastroenterology and Nutrition ServiceDepartment of MedicineMemorial Sloan Kettering Cancer CenterNew York, New York

Julian C. Schink, MDProfessor Department of Obstetrics and GynecologyMichigan State UniversityVice PresidentClinical Integrations and ImprovementSpectrum HealthGrand Rapids, Michigan

Angeles A. Secord, MD, MHSc

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ProfessorDepartment of Obstetrics and GynecologyDivision of Gynecologic OncologyDuke Cancer InstituteDurham, North Carolina

Jeffrey D. Seidman,* MDMedical OfficerOffice of In Vitro Diagnostics and Radiological HealthCenter for Devices and Radiological HealthFood and Drug AdministrationSilver Spring, Maryland

Priya Simoes, MDFellowGastroenterology and Nutrition ServiceMemorial Sloan Kettering Cancer CenterNew York, New York

Yukio Sonoda, MDProfessorDepartment of Obstetrics and GynecologyWeill Cornell Medical CollegeAttending SurgeonDepartment of SurgeryMemorial Sloan Kettering Cancer CenterNew York, New York

Margaret M. Steinhoff, MD FACPProfessor of Pathology and Laboratory MedicineThe Warren Alpert Medical School of Brown UniversityDirector of Surgical PathologyWomen and Infants Hospital of Rhode IslandProvidence, Rhode Island

Paul H. Sugarbaker, MD, FACS, FRCSDirectorProgram in Peritoneal Surface MalignancyMedStar Washington Hospital CenterWashington, DC

C. James Sung, MDProfessor of PathologyAlpert Medical School of Brown UniversityVice Chief of Pathology and Director of Clinical Pathology

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Women and Infants Hospital of Rhode IslandDirector of Clinical Pathology and Laboratory InformaticsCare New England Health SystemProvidence, Rhode Island

Carmen Tornos, MDProfessor of PathologyDepartment of PathologyStony Brook Medical CenterStony Brook, New York

Britton Trabert, PhDInvestigatorDivision of Cancer Epidemiology and GeneticsNational Cancer InstituteBethesda, Maryland

Akila Viswanathan, MD, MPHAssociate Professor of Radiation OncologyHarvard Medical SchoolDirectorGynecologic RadiationDana-Farber Cancer InstituteBoston, Massachusetts

Edward J. Wilkinson, MD, FACOG, FACAPProfessor and Vice ChairmanDirector and ChiefDivision of Anatomic PathologyDepartment of Pathology and Laboratory MedicineAdjunct ProfessorObstetrics and GynecologyUniversity of Florida College of MedicineGainesville, Florida

Aaron H. Wolfson, MDProfessorDepartment of Radiation OncologyUniversity of Miami School of MedicineMiami, Florida

Catheryn Yashar, MDProfessorChief of Breast and Gynecologic ServicesMedical Director La Jolla

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University of California, San DiegoSan Diego, California

Anna Yemelyanova, MDAssociate ProfessorDepartment of PathologyThe University of Texas MD Anderson Cancer CenterHouston, Texas

Robert H. Young, MDRobert E. Scully Professor of PathologyHarvard Medical SchoolDirectorGynecologic PathologyPathologistDepartment of PathologyMassachusetts General HospitalBoston, Massachusetts

Dmitriy Zamarin, MD, PhDAssistant AttendingGynecologic Medical OncologyMemorial Sloan Kettering Cancer CenterNew York, New York

Oliver Zivanovic, MDAssistant ProfessorDepartment of Obstetrics and GynecologyWeill Cornell Medical CollegeAssistant Attending SurgeonDepartment of SurgeryMemorial Sloan Kettering Cancer CenterNew York, New York

*The opinions and assertions herein are the private views of the authors anddo not purport to reflect the US FDA, Department OF HHS, or any other part ofthe US Government. This work was not prepared as part of Dr. Seidman’sofficial duties in the US FDA.

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Video List

Vulva:

Video 1 Sentinel inguinofemoral lymph node identification in vulvar cancer and the use of near-

infrared imaging for sentinel lymph node detection

Cervix:

Video 2 Radical abdominal trachelectomy

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Video 3 Extraperitoneal lymph node dissection

Video 4 Robotic-assisted supralevator total pelvic exenteration

Video 5 Total pelvic infralevator exenteration using Ligasure

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Video 6 Urinary reconstruction following cystectomy: The ileal conduit

Video 7 Urinary reconstruction after pelvic exenteration: Modified Indiana pouch

Video 8 Modified RAM flap for neovagina creation after exenteration

Uterine Corpus:

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Video 9 Sentinel lymph node mapping for uterine cancer: A practical illustration of injection and

mapping techniques

Video 10 Sentinel lymph node (SNL) mapping using robotic-assisted fluorescence imaging

Ovary:

Video 11 Robotic Xi infra renal aortic node dissection with lower pelvic port placement

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Video 12 Retroperitoneal lymph node dissection (RPLND) for primary ovarian cancer

Video 13 Surgical vascular anatomy on the upper abdomen

Video 14 Vascular and ligamentous attachments

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Video 15 How to approach suspicious lymph nodes on the upper abdomen

Video 16 Resection of tumor from the supragastric lesser sac with peritonectomy

Video 17 Morison pouch peritonectomy in cytoreductive surgery

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Video 18 Diaphragm peritonectomy with resection of Glisson capsule for advanced ovarian cancer

Video 19 Diaphragm peritonectomy with full-thickness resection for advanced ovarian cancer

Video 20 Liver mobilization with diaphragm peritonectomy and liver wedge resection

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Video 21 Excision of tumor along ligament venosum

Video 22 Excision of tumor along ligamentum teres

Video 23 Mobilization of right liver with wedge resection segments 6 and 7

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T

Preface

he publication in 2017 of the 7th edition of Principles and Practice of Gynecologic Oncology marks the 25thanniversary of the creation of this textbook. The founding editors, William J. Hoskins, Carlos A. Perez, and RobertC. Young, represented the disciplines of Gynecologic Oncology, Radiation Oncology, and Medical Oncology. They

created the first multidisciplinary textbook in the field and, in their words, “strove to produce a definitive reference writtenat the expert level.” The focus on multidisciplinary approaches to treatment and a detailed presentation of the literature onwhich clinical care is based continues to be a guiding principle.

The second set of editors, Richard R. Barakat, Maurie Markman, and Marcus Randall, also represented Gynecologic,Medical, and Radiation Oncology. Over the course of several editions, they incorporated new chapters that reflecteddramatic progress in the understanding and treatment of women’s cancers. Simultaneously, advances in technologyfacilitated the use of full color throughout the book as well as increasingly user-friendly online versions that allow accessto cutting-edge information at the point of care.

As the new editors of Principles and Practice of Gynecologic Oncology, we owe a debt of gratitude to ourpredecessors. We are proud to continue their tradition of bringing together multidisciplinary expertise that also includesPathology colleagues. Given the pace of discovery and change within the field, we strove to ensure that this new editionreflects the many advances in the field. To this end, this edition includes an updated chapter on pharmacology ofgynecologic cancers and a new chapter on targeted therapies. Several approaches have been developed with collaborationand support from the publisher that will enhance the value of this book for practitioners, researchers, and students.

We are increasingly becoming a single worldwide Gynecologic Oncology community. In recognition of this reality, themost significant change in the 7th edition is an enhanced global focus. This is in dramatic contrast to 25 years ago whenthis textbook was essentially intended to reflect the standard of care and ongoing advancement of knowledge in thedeveloped world. Today, developed nations have embraced global efforts to eradicate health care disparities. The greatestchallenge in Gynecologic Oncology globally is the lack of infrastructure for cervical cancer screening and prevention inresource-poor countries. This results in the deaths of hundreds of thousands of women annually, many of which could beprevented. Treatment of gynecologic cancers also continues to be suboptimal in many of these countries owing to lack ofresources and trained personnel, and this leads to unacceptably low cure rates. In the new edition of Principles andPractice of Gynecologic Oncology, we invited more international experts as authors of chapters to provide theirperspectives on patterns of incidence, mortality, and treatment worldwide. We also established an International EditorialBoard that was charged with providing commentary on similarities and differences in management between differentcountries.

We have given considerable thought to the issue of how best to maintain the relevance of the book between printededitions in an era of instant access to new information on the Internet. Solutions include smartphone access to the contentof the textbook with enhanced search capabilities, as well as more frequent online updates as new studies are reported. Wealso now include online access to a new library of surgical videos to ensure that surgical techniques are not only read, butvisualized.

It is our hope that the global focus of the 7th edition will enhance the impact of this textbook by bringing a synthesis ofexisting knowledge and standards of practice to the entire world. All of those involved in producing this edition are unitedwith its readers in a shared mission to cure and eradicate gynecologic cancers worldwide.

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Dennis S. Chi, MDAndrew Berchuck, MDCatheryn Yashar, MD

Don S. Dizon, MD, FACP

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T

Acknowledgments

he editors acknowledge the contributions of numerous individuals without whom this book would not have beenpossible. The talented staff of the publisher Wolters Kluwer, specifically senior product manager Emilie Moyer,editorial coordinator David Murphy, and developmental editor Martha Cushman, provided invaluable encouragement,

direction, and guidance during the creative process and in technical execution. Shailaja Subramanian provided outstandingproduction services. From the Academic the creative process and in technical execution. Shailaja Subramanian providedoutstanding production services. From the Academic Office of the Gynecology Service, Department of Surgery, MemorialSloan Kettering Cancer Center, we acknowledge the invaluable contributions of editors George Monemvasitis and JeniferLevin. Their attention to detail, patience, and communication skills were of the utmost importance throughout thepublication process. Our appreciation for all their efforts cannot be adequately expressed, but we hope they know howmuch we value their contributions.

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Contents

Covers

Title

Copyright

Dedication

International Editorial Board

Contributors

Video List

Preface

Acknowledgments

SECTION I

ETIOLOGY, PREVENTION, AND MOLECULAR BIOLOGY

1 Epidemiology of Gynecologic CancersLouise A. Brinton, Vikrant V. Sahasrabuddhe, Britton Trabert,and Silvia Franceschi

2 Molecular Pathogenesis of Gynecologic CancersAndrew Berchuck, Douglas A. Levine, Dariush Etemadmoghadam, andDavid D. L. Bowtell

3 Hereditary Gynecologic CancersNoah D. Kauff, Andrew Berchuck, and Karen H. Lu

4 Invasion, Metastasis, and AngiogenesisAngeles A. Secord, Charlie Gourley, and Elise C. Kohn

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5 Development and Identification of Tumor Serum MarkersAleksandra Gentry-Maharaj and Usha Menon

6 Cancer Prevention StrategiesMary B. Daly and Gina M. Mantia-Smaldone

7 Preinvasive Disease of the Lower Genital TractBritt K. Erickson, Mark H. Einstein, and Warner K. Huh

SECTION II

DIAGNOSTIC AND THERAPEUTIC MODALITIES

8 Perioperative and Critical CareJames J. Burke II, Scott C. Purinton, and Heather MacNew

9 Surgical Principles in Gynecologic OncologyYukio Sonoda, David Cibula, Denis Querleu, Eric Leblanc, andOliver Zivanovic

10 Diagnostic ImagingShaunagh McDermott, Leslie K. Lee, and Susanna I. Lee

11 Biologic and Physical Principles of Radiation OncologyBeth A. Erickson, Meena Bedi, Firas Mourtada, and Sunil J.Advani

12 Targeted Therapies in Gynecologic CancersStephanie Lheureux and Amit M. Oza

13 Principles of Chemotherapy in Gynecologic CancerStéphanie L. Gaillard and Michael A. Bookman

14 Pharmacology and Therapeutics in Gynecologic CancerDavid S. Alberts, Hilary Calvert, Maria Lluria-Prevatt, Paul H.Sugarbaker, and Bradley J. Monk

15 Immunotherapy of Gynecologic MalignanciesPaul J. Sabbatini, Kunle Odunsi, Jacobus Pfisterer, and DmitriyZamarin

16 Clinical Trials Methodology and Biostatistics

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Mark F. Brady, Jeffrey C. Miecznikowski, and Virginia L.Filiaci

17 Cost-Effective and Value-Based Gynecologic Cancer CareLaura J. Havrilesky, Shalini L. Kulasingam, Elizabeth L.Jewell, and David E. Cohn

SECTION III

DISEASE SITES

18 VulvaEmily Penick, Sushil Beriwal, Edward J. Wilkinson, and John W.Moroney

19 Vaginal CancerJosephine Kang, Amanda N. Fader, and Akila Viswanathan

20 Cervix UteriCharles A. Kunos, Fadi W. Abdul-Karim, Don S. Dizon, and RobertDebernardo

21 Corpus: Epithelial TumorsSusana M. Campos, Larissa J. Lee, Marcela G. Del Carmen, and D.Scott McMeekin

22 Corpus: Mesenchymal TumorsMario M. Leitao Jr, Carmen Tornos, Aaron H. Wolfson, and RoisinO’Cearbhaill

23 Epithelial Ovarian CancerGini F. Fleming, Jeffrey D. Seidman, Anna Yemelyanova, andErnst Lengyel

24 Ovarian Germ Cell TumorsDaniela Matei, Robert E. Emerson, and Jubilee Brown

25 Ovarian Sex Cord–Stromal TumorsDavid M. Gershenson, Sean C. Dowdy, and Robert H. Young

26 Gestational Trophoblastic Disease: Molar PregnancyandGestational Trophoblastic Neoplasia

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