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Anal Cancer A Comprehensive Guide Jeffrey Meyer Lisa Kachnic Editors 123 Anal Cancer Jeffrey Meyer • Lisa Kachnic Editors Anal Cancer A Comprehensive Guide Editors Jeffrey Meyer, MD, MS Lisa Kachnic, MD, FASTRO Department of Radiation Oncology Department of Radiation Oncology Johns Hopkins School of Medicine Vanderbilt University School of Medicine Baltimore, MD, USA Nashville, TN, USA ISBN 978-3-030-20252-1 ISBN 978-3-030-20253-8 (eBook) https://doi.org/10.1007/978-3-030-20253-8 © Springer Nature Switzerland AG 2019 This work is subject to copyright. All rights are reserved by the Publisher, whether the whole or part of the material is concerned, specifically the rights of translation, reprinting, reuse of illustrations, recitation, broadcasting, reproduction on microfilms or in any other physical way, and transmission or information storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodology now known or hereafter developed. The use of general descriptive names, registered names, trademarks, service marks, etc. in this publication does not imply, even in the absence of a specific statement, that such names are exempt from the relevant protective laws and regulations and therefore free for general use. The publisher, the authors, and the editors are safe to assume that the advice and information in this book are believed to be true and accurate at the date of publication. Neither the publisher nor the authors or the editors give a warranty, expressed or implied, with respect to the material contained herein or for any errors or omissions that may have been made. The publisher remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. This Springer imprint is published by the registered company Springer Nature Switzerland AG The registered company address is: Gewerbestrasse 11, 6330 Cham, Switzerland I dedicate this book to the many patients that I have had the privilege to care for during my career. They have all shaped me into the physician and person I am today, and I hope that I have positively touched their lives in return. Lisa Kachnic Preface A multidisciplinary team approach is paramount to the management of anal cancer; however, due to its low incidence as compared to other solid cancers, there are lim- ited comprehensive published treatment guidelines. This need has become increas- ingly important over the past several years when we have seen advances in the prevention, detection, radiation delivery, and systemic approaches including immunotherapy. As a result, it is currently very difficult for a clinician (either in training or in practice) to gain experience and expertise in the multidisciplinary management of this rare cancer. Anal Cancer: A Comprehensive Guide was created for the purpose of centralizing the knowledge and experience of experts across a variety of disci- plines. The authors provide an overview of the principles of disease pathogenesis, anatomy, epidemiology, and staging, in addition to detailed established and cutting- edge clinical approaches for the treatment of anal cancer. Foundations, current evidence-b ased practices, and pathways for the future are the focus. Our vision is that this book may be used to serve as a definitive and comprehensive resource for the team-based management of all stages and histologies of anal cancer. We thank our gracious contributors for lending their expertise toward the improved care of our patients. Baltimore, MD, USA Jeffrey Meyer Nashville, TN, USA Lisa Kachnic vii Contents 1 Anatomy and Histology of the Anus . . . . . . . . . . . . . . . . . . . . . . . . . . . 1 Margaret H. Sundel, Lysandra Voltaggio, Ira L. Leeds, and Sandy Hwang Fang 2 Epidemiology and Pathogenesis of Anal Cancer . . . . . . . . . . . . . . . . . 11 John David Roveda Jr and Clayton A. Smith 3 Staging and Initial Evaluation of Anal Cancer . . . . . . . . . . . . . . . . . . 33 Apar Gupta, Shang-Jui Wang, and Salma K. Jabbour 4 Treatment of Localized Anal Cancer: Chemoradiotherapy . . . . . . . . 47 James Byrne and Jennifer Y. Wo 5 Anal Cancer: Toxicities and Management . . . . . . . . . . . . . . . . . . . . . . 71 Shalini Moningi and Prajnan Das 6 Management of Local-Regional Anal Cancer Recurrence . . . . . . . . . 85 Shilpa S. Murthy and Elin R. Sigurdson 7 Treatment of Advanced Anal Cancer . . . . . . . . . . . . . . . . . . . . . . . . . . 95 Satya Das and Kristen Keon Ciombor 8 Treatment of Non-squamous Histologies in Anal Cancer . . . . . . . . . . 113 Matthew T. Ballo 9 Diagnosis and Management of Perianal Skin Tumors . . . . . . . . . . . . . 123 Monica Polcz, A. Bapsi Chakravarthy, and Christina Edwards Bailey Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 133 ix Contributors Christina Edwards Bailey, MD, MSCI Department of Surgery, Vanderbilt University Medical Center, Nashville, TN, USA Matthew T. Ballo, MD Department of Radiation Oncology, West Cancer Center, Memphis, TN, USA James Byrne, MD, PhD Harvard Radiation Oncology Program, Boston, MA, USA A. Bapsi Chakravarthy, MD, FASTRO Department of Radiation Oncology, Vanderbilt University Medical Center, Nashville, TN, USA Kristen Keon Ciombor, MD, MSCI Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Prajnan Das, MD, MS, MPH Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Satya Das, MD Division of Hematology/Oncology, Department of Internal Medicine, Vanderbilt University Medical Center, Nashville, TN, USA Sandy Hwang Fang, MD Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Apar Gupta, MD Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Roberts Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA Salma K. Jabbour, MD Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Roberts Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA xi xii Contributors Ira L. Leeds, MD, MBA, ScM Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Shalini Moningi, MD Department of Radiation Oncology, University of Texas MD Anderson Cancer Center, Houston, TX, USA Shilpa S. Murthy, MD, MPH Department of Surgical Oncology, Fox Chase Cancer Center, Temple University, Philadelphia, PA, USA Monica Polcz, MD Department of General Surgery, Vanderbilt University Medical Center, Nashville, TN, USA John David Roveda Jr, BS University of South Alabama College of Medicine, Mobile, AL, USA Elin R. Sigurdson, MD, PhD Department of Surgical Oncology, Fox Chase Cancer Center, Temple University, Philadelphia, PA, USA Clayton A. Smith, MD, PhD Department of Radiation Oncology, Ochsner Medical Center, New Orleans, LA, USA Margaret H. Sundel, BS Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Lysandra Voltaggio, MD Division of Gastrointestinal and Liver Pathology, Johns Hopkins, Baltimore, MD, USA Shang-Jui Wang, MD, PhD Department of Radiation Oncology, Robert Wood Johnson University Hospital, New Brunswick, NJ, USA Department of Radiation Oncology, Rutgers Cancer Institute of New Jersey, Roberts Wood Johnson Medical School, Rutgers University, New Brunswick, NJ, USA Jennifer Y. Wo, MD Department of Radiation Oncology, Massachusetts General Hospital, Harvard University School of Medicine, Boston, MA, USA Chapter 1 Anatomy and Histology of the Anus Margaret H. Sundel, Lysandra Voltaggio, Ira L. Leeds, and Sandy Hwang Fang Abbreviations RAIR Rectoanal inhibitory reflex S2–S4 Sacral nerves S2–S4 Definitions of the Anal Canal The anal canal is the final portion of the large intestine, connecting the rectum to the external opening of the anus. There are many ways to define the anal canal, each of which relies on different anatomic landmarks (Table 1.1). The pelvic floor is the muscular layer that separates the pelvic cavity from the perineal region and provides support to the pelvic viscera. The dentate line (or pectinate line) is a visibly scal- loped border overlying the anal columns of Morgagni, located at the embryological transition from hindgut to proctodeum, i.e., the squamocolumnar junction. The 1–1.5 cm portion of the anal canal proximal to the dentate line is called the anal pecten or transitional zone. The transitional zone contains a conglomeration of both squamous epithelial cells and columnar cells. The anal sphincter complex is com- posed of the internal and external anal sphincters. The anal verge is the terminal portion of the anal canal, where the squamous epithelium of the canal (anoderm) meets the perianal skin. M. H. Sundel · I. L. Leeds · S. H. Fang (*) Department of Surgery, The Johns Hopkins University School of Medicine, Baltimore, MD, USA e-mail: [email protected]; [email protected]; [email protected] L. Voltaggio Division of Gastrointestinal and Liver Pathology, Johns Hopkins, Baltimore, MD, USA e-mail: [email protected] © Springer Nature Switzerland AG 2019 1 J. Meyer, L. Kachnic (eds.), Anal Cancer, https://doi.org/10.1007/978-3-030-20253-8_1