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Penile Cancer Published by the Société Internationale d’Urologie (SIU) SIU Central Office 1155 University Street, Suite 1155 Montreal QC Canada H3B 3A7 Tel: +1 514 875 5665 Fax: +1 514 875 0205 E-mail: [email protected] © 2009 Société Internationale d’Urologie (SIU) ISBN: 978-0-620-44542-9 Layout and design by: Thea Brits (Boss Design Repro & Print) Printed and bound by: CTP Book Printers, Cape Town, South Africa All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted in any form or by any means, electronic, mechanical, photocopying, recording, or otherwise, without the prior written permission of the publisher. Every effort has been made to trace copyright holders. We, the publisher, apologize for any errors or omissions, and invite copyright holders to contact us if any have occurred, so that we can rectify them. Accurate indications, adverse reactions and dosage schedules for drugs are provided in this book, but it is possible that they may change. The reader is urged to review the package information data of the manufacturer of the medications mentioned. PREFACE n the majority of developed countries, cancer of the penis is an uncommon disease, but it is a significant health and social problem in regions of Africa, Asia, and South America. Squamous cell carcinoma, the most frequent penile cancer, is a malignancy where the behavior is commonly Ipredictable and cure, in initial stages, may be achieved in many instances by partial or total penectomy. On the other hand, more advanced disease comprising regional lymph node or distant metastases has worse and unpredictable outcomes. There are many controversies regarding the management of all aspects of this cancer, including prevention, staging, treatment options and health policy. The International Consultation on Penile Cancer was designed to present state-of-the-art information on, and understanding of the many aspects of this neoplasia that factor into decisions related to its assessment and therapy. It represents the consensus recommendations of the 8 committees that met in Milan (2008), Santiago (2008) and Chicago (2009) on the occasion of EAU, SIU and AUA meetings. The task of the committee members was to review the literature based on the best evidence, write a text overview of each chapter and finally make recommendations. On behalf of the ICUD and its steering Committee we want to thank the chairmen and members, composed of representatives of the major urological associations (SIU, AUA, EAU, UAA, CAU) for meeting the highest expectations. Now it is time to share this textbook with the readers in the hope that the concepts contained will prove useful as information base in approaching their patients and also as stimulation for further studies. We are very grateful to Drs. Saad Khoury and Paul Abrams of the SIU for having permitted us to organize and edit this book. Antonio Carlos L. Pompeo, MD, Professor of Urology, ABC Medical School, São Paulo, Brazil, SIU-ICUD Chairman Chris Heyns, MD, Professor of Urology, University of Stellenbosch and Tygerberg Hospital, South Africa, SIU-ICUD Co-Chairman Paul Abrams, MD, Professor of Urology, Bristol Urological Institute, Southmead Hospital, Bristol, United Kingdom, SIU Consensus and Education Committee Chairman Antonio Pompeo Chris Heyns Paul Abrams iii iv MEMBERS Antonio Carlos Lima Pompeo Chairman Chris Heyns Co-chairman Committee 1 Epidemiology and natural history of penile cancer ..................................... 1 Mariela Pow-Sang (Peru) Aguinaldo Nardi (Brazil) Julio Pow-Sang (USA) Ubirajara Ferreira (Brazil) Victor Destefano (Peru) Committee 2 Developments in the pathology of penile cancer ......................................... 15 Antonio Cubilla (Paraguay) Alcides Chaux (Paraguay) Elsa Velázquez (USA) Ferran Algaba (Spain) Gustavo Ayala (USA) Committee 3 Penile cancer prevention and pre-malignant lesions .................................. 35 Suks Minhas (United Kingdom) Andreas Manseck (Germany) Paul Hegarty (United Kingdom) Stephen Watya (Uganda) Committee 4 Diagnosis and staging of penile cancer ......................................................... 71 Arturo Mendoza-Valdés (México) Chris Heyns (South Africa) Antonio Pompeo (Brazil) Committee 5 New developments in the treatment of localized penile cancer .................. 101 Eduardo Solsona (Spain) Amit Bahl (United Kingdom) Steven Brandes (USA) David Dickerson (United Kingdom) Antonio Puras-Baez (Puerto Rico) Hein Van Poppel (Belgium) Nick Watkin (United Kingdom) v Committee 6 Management of the lymph nodes in penile cancer ....................................... 129 Chris Heyns (South Africa) Neil Fleshner (Canada) Vijay Sangar (England) Boris Schlenker (Germany) Yuvaraja Thyavihally (India) Hein van Poppel (Belgium) Committee 7 Treatment of visceral or bulky/unresectable regional metastases of penile cancer ................................................................................................ 175 Curtis Pettaway (USA) Lance Pagliaro (USA) Christine Theodore (France) Gabriel Haas (USA) Committee 8 Prognostic factors in penile cancer ................................................................ 193 Vincenzo Ficarra (Italy) Bulent Akduman (Canada) Olivier Bouchot (France) Joan Palou (Spain) Marcos Tobias-Machado (Brazil) vi Some members of the SIU / ICUD Penile Cancer Consultation, Santiago, Chile, November 2008 Front row: Chris Heyns, Eduardo Solsona, Marcos Tobias-Machado, Antonio Pompeo, Mariela Pow-Sang, Boris Schlenker Second row: Vijay Sangar, Yuvaraja Thyavihally, Vincenzo Ficarra, Hein van Poppel, Susanne Osanto Third row: Antonio Puras-Baez, Antonio Cubilla, Arturo Mendoza-Valdés, Stephen Watya, Andreas Manseck Fourth row: Rowland Rees, Suks Minhas, Alexandre Pompeo, Curtis Pettaway vii Summary of the International Consultation on Urologic Disease Modified Oxford System for Levels of Evidence and Grades of Recommendation* Levels of Evidence (LE) Level 1 Metanalysis of randomized controlled trials (RCTs) or a good quality RCT Level 2 Low quality RCT or metanalysis of good quality prospective cohort studies Level 3 Good quality retrospective case control studies or case series Level 4 Expert opinion based on “first principles” or bench research, not on evidence Grades of Recommendation (GR) Grade A Usually consistent level 1 evidence Grade B Consistent level 2 or 3 evidence or “majority evidence” from RCTs Grade C Level 4 evidence, “majority evidence” from level 2/3 studies, expert opinion Grade D No recommendation possible because of inadequate or conflicting evidence * Adapted from Evidence-Based Medicine. Oxford University. Overview of the main steps for developing and grading guideline recommendations, by P. Abrams, A. Grant, and S. Khoury, January 2004. viii x Committee 1 Epidemiology and Natural History of Penile Cancer Chair Mariela Pow-Sang (Peru) Members Aguinaldo Nardi (Brazil) Julio Pow-Sang (USA) Ubirajara Ferreira (Brazil) Victor Destefano (Peru) 1 CONTENTS Epidemiology and Natural History of Penile Cancer Epidemiology ................................................................................................................................... 3 Risk factors ...................................................................................................................................... 3 Phimosis• Phimosis• ...................................................................................................................................... 3 • Circumcision ............................................................................................................................... 4 • Cigarette smoking ....................................................................................................................... 5 • Injury to the penis and chronic balanitis ..................................................................................... 5 • Genital warts ............................................................................................................................... 6 • HPV infection ............................................................................................................................. 6 Natural history ................................................................................................................................. 8 References ........................................................................................................................................ 12 2 Epidemiology and Natural History of Penile Cancer M. Pow-Sang A. C. Nardi, J. M. Pow-Sang, U. Ferreira, V. Destefano Epidemiology • Incidence rate for primary malignant penile cancer has decreased in the United States, Primary malignant penile cancer is a rare disease. Uganda, Finland and Jamaica (LE 4). Penile cancer incidence varies among differ- • Penile cancer affects men between 50 and 70 ent populations, and it is rare in most developed years of age (LE 4). nations. In the United States, age-standardized • There is an increase in incidence of regional incidence rates range from 0.3 to 1.8/100,000 disease in recent years (LE 4). inhabitants.1 Higher incidence rates are seen • There is familial association of penile cancer in underdeveloped countries, such as Uganda (LE 4). (2,8/100,000), and in areas of Brazil (1.5 – 3.7/100,000); the lowest incidence world-wide is reported in Israeli Jews (0.1/100,000).1 Risk factors The overall age-adjusted incidence rate for pri- Case-control studies have shown the association of mary,
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