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  • 1. AJCCCANCER STAGING MANUAL Seventh Edition
  • 2. EDITORIAL BOARD STEPHEN B. EDGE, m.d., f.a.c.s., Editor Roswell Park Cancer Institute Buffalo, New York DAVID R. BYRD, m.d., f.a.c.s.,University of Washington School of Medicine Seattle, Washington CAROLYN C. COMPTON, m.d., ph.d. National Cancer Institute Bethesda, Maryland APRIL G. FRITZ, r.h.i.t., c.t.r. A. Fritz and Associates Reno, Nevada FREDERICK L. GREENE, m.d., f.a.c.s. Carolinas Medical Center Charlotte, North Carolina ANDY TROTTI, III, m.d. H. Lee Moffitt Cancer Center Tampa, Florida
  • 3. AJCCCANCER STAGING MANUAL Seventh Edition AMERICAN JOINT COMMITTEE ON CANCER Executive Office 633 North Saint Clair Street Chicago, IL 60611-3211This manual was prepared and published through the support of the American Cancer Society, theAmerican College of Surgeons, the American Society of Clinical Oncology, the Centers forDisease Control and Prevention, and the International Union Against Cancer. CD-ROM Included
  • 4. American Joint Committee on CancerExecutive Office633 North Saint Clair StreetChicago, IL 60611-3211EditorsStephen B. Edge, m.d., f.a.c.s. April G. Fritz, r.h.i.t., c.t.r.Roswell Park Cancer Institute A. Fritz and AssociatesBuffalo, NY, USA Reno, NV, USADavid R. Byrd, m.d., f.a.c.s. Frederick L. Greene, m.d., f.a.c.s.University of Washington School of Medicine Carolinas Medical CenterSeattle, WA, USA Charlotte, NC, USACarolyn C. Compton, m.d., ph.d. Andy Trotti, III, m.d.National Cancer Institute H. Lee Moffitt Cancer CenterBethesda, MD, USA Tampa, FL, USAISBN 978-0-387-88440-0Springer New York Dordrecht Heidelberg LondonLibrary of Congress Control Number: 2009930462First to Fifth Editions of the AJCC Cancer Staging Manual, published by Lippincott Raven Publishers, Philadelphia.PA.Sixth Edition of the AJCC Cancer Staging Manual, published by Springer-Verlag, New York, NY.Seventh Edition © 2010 American Joint Committee on Cancer. All rights reserved. The AJCC Cancer StagingManual is the Official Publication of the American Joint Committee on Cancer.This book consists of a printed book and a CD-ROM packaged with the book, both of which are protected byfederal copy-right law and international treaty. The book, except for the Staging Forms, may not be translated orcopied in whole or in part without the written permission of the publisher (Springer Science + Business MediaLLC, 233 Spring Street, New York, NY 10013, USA), or the copyright holder, except for brief excerpts in connectionwith reviews or scholarly analysis. For copyright information regarding the CD-ROM, please consult the printedinformation packaged with the CD-ROM in the back of this publication. Use in connection with any form ofinformation storage and retrieval, electronic adaptation, computer software, or by similar or dissimilar methodo-logy now known or hereafter developed is forbidden.Materials appearing in this book prepared by individuals as part of their official duties as U.S. Governmentemployees are not covered by the above-mentioned copyright.The use in this publication of trade names, trademarks, service marks, and similar terms, even if they are notidentified as such, is not to be taken as an expression of opinion as to whether or not they are subject to proprietaryrights.While the advice and information in this book are believed to be true and accurate at the date of going to press,neither the authors nor the editors nor the publisher nor the AJCC can accept any legal responsibility for anyerrors or omissions that may be made. The publisher makes no warranty, express or implied, with respect to thematerial contained therein.Printed on acid-free paperSpringer is part of Springer Science+Business Media (www.springer.com)
  • 5. SEVENTH EDITION Dedicated to Irvin D. Fleming, m.d. SIXTH EDITION Dedicated to Robert V. P. Hutter, m.d. FIFTH EDITION Dedicated to Oliver Howard Beahrs, m.d. FOURTH EDITION Dedicated to the memory of Harvey Baker, m.d. THIRD EDITION Dedicated to the memory of W. A. D. Anderson, m.d. Marvin Pollard, m.d. Paul Sherlock, m.d. SECOND EDITION Dedicated to the memory of Murray M. Copeland, m.d. Seventh Edition DedicationThis seventh edition of the AJCC Cancer Staging Manual is on Cancer, the National Cancer Registrars Association, anddedicated to Irvin D. Fleming. Dr. Fleming is a past Chair the North American Association of Central Cancer Registries.of the AJCC and a giant in American oncology. The major Dr. Fleming’s influence on cancer care and commitment tochanges in cancer staging being introduced with this edition patients extends well beyond the AJCC as evidenced by hisare largely the outgrowth of Dr. Fleming’s vision in estab- leadership in many organizations, including service as Presi-lishing a landmark collaboration between the AJCC and dent of the American Cancer Society. For his vision, leader-the National Cancer Institute SEER Program, the National ship, friendship, and support, we dedicate this Manual in hisProgram for Cancer Registries of the CDC, the Commission honor.American Joint Committee on Cancer • 2010 v
  • 6. PrefaceCancer staging plays a pivotal role in the battle on cancer. It The level of data supporting the staging systems var-forms the basis for understanding the changes in population ies among disease sites. For some diseases, particularly lesscancer incidence, extent of disease at initial presentation, and common cancers, there are few outcome data available. Thesethe overall impact of improvements in cancer treatment. Stag- staging systems are based on what limited data are avail-ing forms the base for defining groups for inclusion in clinical able, supplemented by expert consensus. Though potentiallytrials. Most importantly, staging provides those with cancer and imperfect, these disease schemas are critical to allow the col-their physicians the critical benchmark for defining prognosis lection of standardized data to support clinical care and forand the likelihood of overcoming the cancer and for determin- future evaluation and refinement of the staging system.ing the best treatment approach for their cases. Increasingly, the disease teams of the AJCC and UICC use Refining these standards to provide the best possible existing data sets or establish the necessary collaborations tostaging system is a never-ending process. Toward this end, develop new large data sets to provide high-level evidencethe American Joint Committee on Cancer (AJCC) has led to support changes in the staging system. Examples of thisthese efforts in the USA since 1959. A collaborative effort include the work in melanoma that led to changes in the sixthbetween the AJCC and the International Union for Cancer edition and their refinement in this seventh edition, use ofControl (UICC) maintains the system that is used worldwide. the National Cancer Data Base and Surveillance Epidemiol-This system classifies the extent of disease based mostly on ogy and End Results (SEER) data base for evaluation of theanatomic information on the extent of the primary tumor, colorectal staging system, and the use of existing data setsregional lymph nodes, and distant metastases. This classifica- from the USA, Europe, and Asia in gastric cancer. In addition,tion was developed in the 1940s by Pierre Denoix of France groups have been established to collect very large interna-and formalized by the UICC in the 1950s with the formation tional data sets to refine staging. In addition to the melanomaof the Committee on Clinical Stage Classification and Applied collaborative, the best examples in refining staging for theStatistics. The AJCC was founded in 1959 to complement this seventh edition are the collaborative group of the Interna-work. The AJCC published its first cancer staging manual in tional Association for the Study of Lung Cancer (IASLC) and1977. Since the 1980s, the work of the UICC and AJCC has the Worldwide Esophageal Cancer Collaborative (WECC).been coordinated, resulting in the simultaneous publication A major challenge to TNM staging is the rapid evolu-of the TNM Classification of Malignant Tumours by the UICC tion of understanding in cancer biology and the availabilityand the AJCC Cancer Staging Manual. The revision cycle is of biologic factors that predict cancer outcome and response6–8 years, a time frame that provides for accommodation of to treatment with better accuracy than purely anatomicallyadvances in cancer care while allowing cancer registry systems based staging. This has led some cancer experts to concludeto maintain stable operations. that TNM is obsolete. Although such statements are mis- The work of the AJCC is made possible by the dedicated guided, the reality is that the anatomic extent of disease onlyvolunteer effort of hundreds, and perhaps thousands, of com- tells part of the story for many cancer patients.mitted health professionals including physicians, nurses, popu- The question of including nonanatomic prognostic fac-lation scientists, statisticians, cancer registrars, supporting staff, tors in staging has led to intense debate about the purpose andand others. These volunteers, representing all relevant disci- structure of staging. Beginning with the sixth edition of theplines, are organized into disease teams chaired by leading cli- AJCC Cancer Staging Manual, there was judicious addition ofnicians. These teams make recommendations for change in the nonanatomic factors to the classifications that modified stagestaging system based on available evidence supplemented with groups. This shift away from purely anatomic informationexpert consensus. Supporting these teams is a panel of expert has been extended in the current edition. Relevant markersstatisticians who provide critical support in evaluation of exist- that are of such importance that they are required for clini-ing data and in analysis of new data when this is available. cians to make clear treatment decisions have been includedAmerican Joint Committee on Cancer • 2010 vii
  • 7. in groupings. Examples include the mitotic rate in staging manual were adopted for application to cases diagnosed on orgastrointestinal stromal tumors and prostate-specific antigen after January 1, 2010.and Gleason score in staging prostate cancer. In the future, the This work involved many professionals in all fields indiscovery of new markers will make it necessary to include the clinical oncology, cancer registry, population surveil-these markers in staging and will likely require the develop- lance, and statistical communities. It is hard to single outment of new strategies beyond the current grouping systems. individuals, but certain people were central to this effort. That said, it must also be clearly stated that it is critical Irvin Fleming, to whom we dedicate this Manual, showedto maintain the anatomic base to cancer staging. Anatomic the leadership and the vision over a decade ago that led toextent of disease remains the key prognostic factor in most the development of the Collaborative Stage Data Collectiondiseases. In addition, it is necessary to have clear links to past System. Frederick Greene, as senior editor of the sixth edi-data to assess trends in cancer incidence and the impact of tion, paved the way for this work, developed the extremelyadvances in screening and treatment and to be able to apply popular and useful AJCC Cancer Staging Atlas, and did thestage and compare stage worldwide in situations where new legwork to enhance the collaboration between the UICCnonanatomic factors are not or cannot be collected. There- and AJCC. The work of our publisher Springer provided thefore, the staging algorithms in this edition of the AJCC Cancer resources to support this work and the patience needed asStaging Manual using nonanatomic factors only use them as the Task Forces and editors finished their work. The manymodifiers of anatomic groupings. These factors are not used cancer registrars and the Collaborative Stage Version 2 Workto define the T, N, and M components, which remain purely Group who worked on the disease teams kept us all properlyanatomic. Where they are used to define groupings, there is focused. And the AJCC staff, most notably Donna Gress,always a convention for assigning a group without the non- Karen Pollitt, and Connie Bura provided the glue and theanatomic factor. These conventions have been established and sweat to keep us all together.defined in collaboration with the UICC. We believe that this, the seventh edition of the AJCC The work for the seventh edition of the AJCC Cancer Cancer Staging Manual, and the electronic and print productsStaging Manual began immediately on publication of the built on this manual, will provide strong support to patientssixth edition. Under the leadership of the Prognostic Fac- and physicians alike as they face the battle with cancer, and wetors Task Force of the UICC, an ongoing review of literature hope that it provides the concepts and the foundation for therelevant to staging was performed and updated annually. A future of cancer staging as we move to the era of personalizednew data collection system that allows capture of nonana- molecular oncology.tomic information in conjunction with anatomic staging datawas developed and implemented in the USA. A number ofworking groups continued data collection and analysis with Stephen B. Edge, Buffalo, NYthe plan to advise AJCC Task Forces. The AJCC provided a David R. Byrd, Seattle, WAcompetitive grant program to support work to lead to stag- Carolyn C. Compton, Bethesda, MDing revision. An enhanced statistical task force was empan- April G. Fritz, Reno, NVelled. Finally, in 2006, the disease task forces were convened Frederick L. Greene, Charlotte, NCto review available evidence and recommend changes to Andy Trotti, Tampa, FLTNM. After review by the UICC, the changes reflected in thisviii American Joint Committee on Cancer • 2010
  • 8. Part I..................................................................... 1 General Information on Cancer Staging Brief Contents and End-Results Reporting / 1 by Part Part II ................................................................... 2 Head and Neck / 21 Part III .................................................................. 3 Digestive System / 101 Part IV................................................................... 4 Thorax / 251 Part V .................................................................... 5 Musculoskeletal Sites / 279 Part VI................................................................... 6 Skin / 299 Part VII.................................................................. 7 Breast / 345 Part VIII ................................................................ 8 Gynecologic Sites / 377 Part IX ................................................................... 9 Genitourinary Sites / 445 Part X .................................................................... 10 Ophthalmic Sites / 521 Part XI ................................................................... 11 Central Nervous System / 591 Part XII ......................................................................... 12 Lymphoid Neoplasms / 599 Part XIII ........................................................................ 13 Personnel and Contributors / 629American Joint Committee on Cancer • 2010 ix
  • 9. ContentsDedication .....................................................................v 16. Gastrointestinal Stromal Tumor..........................175Preface ........................................................................ vii 17. Neuroendocrine Tumors .....................................181Brief Contents by Part .................................................ix 18. Liver (Excluding intrahepatic bile ducts) ..............191Introduction and Historical Overview ................... xiii 19. Intrahepatic Bile Ducts ........................................201Part I ...................................................................1 20. Gallbladder ...........................................................211General Information on Cancer Staging 21. Perihilar Bile Ducts ..............................................219and End-Results Reporting 22. Distal Bile Duct ....................................................227 1. Purposes and Principles of Cancer Staging ............3 23. Ampulla of Vater ..................................................235 2. Cancer Survival Analysis ........................................15 24. Exocrine and Endocrine Pancreas .......................241Part II ................................................................21Head and Neck Part IV.............................................................251 Introduction and General Rules ..........................21 Thorax 3. Lip and Oral Cavity ................................................29 25. Lung ......................................................................253 4. Pharynx (Including base of tongue, 26. Pleural Mesothelioma ..........................................271 soft palate, and uvula).............................................41 5. Larynx .....................................................................57 Part V..............................................................279 6. Nasal Cavity and Paranasal Sinuses.......................69 Musculoskeletal Sites 7. Major Salivary Glands 27. Bone ......................................................................281 (Parotid, submandibular, and sublingual)..............79 28. Soft Tissue Sarcoma .............................................291 8. Thyroid ...................................................................87 9. Mucosal Melanoma of the Head and Neck...........97 Part VI.............................................................299 SkinPart III .............................................................101 29. Cutaneous Squamous Cell CarcinomaDigestive System and Other Cutaneous Carcinomas ......................30110. Esophagus and Esophagogastric Junction ..........103 30. Merkel Cell Carcinoma ........................................31511. Stomach ................................................................117 31. Melanoma of the Skin ..........................................32512. Small Intestine ......................................................12713. Appendix ..............................................................133 Part VII ............................................................. 34514. Colon and Rectum ...............................................143 Breast15. Anus ......................................................................165 32. Breast ....................................................................347American Joint Committee on Cancer • 2010 xi
  • 10. Part VIII ..........................................................377 Part X ..............................................................521Gynecologic Sites Ophthalmic Sites Introduction .......................................................377 48. Carcinoma of the Eyelid ......................................52333. Vulva .....................................................................379 49. Carcinoma of the Conjunctiva ............................53134. Vagina ...................................................................387 50. Malignant Melanoma of the Conjunctiva ..........53935. Cervix Uteri ..........................................................395 51. Malignant Melanoma of the Uvea.......................54736. Corpus Uteri .........................................................403 52. Retinoblastoma.....................................................56137. Ovary and Primary Peritoneal 53. Carcinoma of the Lacrimal Gland.......................569 Carcinoma ............................................................419 54. Sarcoma of the Orbit............................................57738. Fallopian Tube ......................................................429 55. Ocular Adnexal Lymphoma.................................58339. Gestational Trophoblastic Tumors ......................437 Part XI .............................................................591 Central Nervous SystemPart IX .............................................................445 56. Brain and Spinal Cord .........................................593Genitourinary Sites40. Penis ......................................................................447 Part XII............................................................599 Lymphoid Neoplasms41. Prostate .................................................................457 57. Lymphoid Neoplasms (A. Hodgkin and Non-Hodgkin42. Testis......................................................................469 Lymphomas, B. Primary Cutaneous Lymphomas,43. Kidney ...................................................................479 C. Multiple Myeloma and Plasma Cell Disorders, and D. Pediatric Lymphoid Malignancy) .............60544. Renal Pelvis and Ureter ........................................49145. Urinary Bladder....................................................497 Part XIII...........................................................629 Personnel and Contributors46. Urethra ..................................................................50747. Adrenal..................................................................515 Index ..........................................................................643xii American Joint Committee on Cancer • 2010
  • 11. Introduction and Historical OverviewThe seventh edition of the AJCC Cancer Staging Manual is review scholarly material related to cancer staging and makea compendium of all currently available information on the recommendations to the AJCC regarding potential changes instaging of cancer for most clinically important anatomic sites. the staging taxonomy.It has been developed by the American Joint Committee on During the last 50 years of activity related to the AJCC,Cancer (AJCC) in cooperation with the TNM Committee of a large group of consultants and liaison organization repre-the International Union Against Cancer (UICC). The two sentatives have worked with the AJCC leadership. These rep-organizations have worked together at every level to create a resentatives have been selected by the American Society ofstaging schema that remains uniform throughout. The cur- Clinical Oncology, the Centers for Disease Control and Pre-rent climate that allows for consistency of staging worldwide vention, the American Urological Association, the Associationhas been made possible by the mutual respect and diligence of American Cancer Institutes, the National Cancer Registrarsof those working in the staging area for both the AJCC and Association, the Society of Gynecologic Oncologists, the Soci-the UICC. ety of Urologic Oncology, the National Cancer Institute and Classification and staging of cancer enable the physician the SEER Program, the North American Association of Cen-and cancer registrar to stratify patients, which leads to better tral Cancer Registries (NAACCR), and the American Societytreatment decisions and the development of a common lan- of Colon and Rectal Surgeons.guage that aids in the creation of clinical trials for the future Chairing the AJCC have been Murray Copeland, M.D.testing of cancer treatment strategies. A common language of (1959–1969), W.A.D. Anderson, M.D. (1969–1974), Oliver H.cancer staging is mandatory in order to realize the important Beahrs, M.D. (1974–1979), David T. Carr, M.D. (1979–1982),contributions from many institutions throughout the world. Harvey W. Baker, M.D. (1982–1985), Robert V. P. Hutter, M.D.This need for appropriate nomenclature was the driving force (1985–1990), Donald E. Henson, M.D. (1990–1995), Irvinthat led to clinical classification of cancer by the League of D. Fleming, M.D. (1995–2000), Frederick L. Greene, M.D.Nations Health Organization in 1929 and later by the UICC (2000–2004), David L. Page, M.D. (2004–2005), Stephen B.and its TNM Committee. Edge, M.D. (2005–2008), and currently Carolyn C. Compton, The AJCC was first organized on January 9, 1959, as M.D., Ph.D.the American Joint Committee for Cancer Staging and End The initial work on the clinical classification of cancerResults Reporting (AJC). The driving force behind the organi- was instituted by the League of Nations Health Organiza-zation of this body was a desire to develop a system of clinical tion (1929), the International Commission on Stage Group-staging for cancer that was acceptable to the American medi- ing and Presentation of Results (ICPR) of the Internationalcal profession. The founding organizations of the AJCC are Congress of Radiology (1953), and the International Unionthe American College of Surgeons, the American College of Against Cancer (UICC). The latter organization became mostRadiology, the College of American Pathologists, the Ameri- active in the field through its Committee on Clinical Stagecan College of Physicians, the American Cancer Society, and Classification and Applied Statistics (1954). This committeethe National Cancer Institute. The governance of the AJCC is was later known as the UICC TNM Committee, which nowoverseen by designees from the founding organizations and includes the Chair of the AJCC.representatives of the sponsoring organizations including Since its inception, the AJCC has embraced the TNM sys-the American Society of Clinical Oncology and the Centers tem in order to describe the anatomic extent of cancer at thefor Disease Control and Prevention. The Medical Director of time of initial diagnosis and before the application of defini-the Commission on Cancer functions as the Executive Direc- tive treatment. In addition, a classification of the stages oftor of the AJCC. Fostering the work of the AJCC has been cancer was utilized as a guide for treatment and prognosisundertaken by committees called task forces, which have been and for comparison of the end results of cancer management.established for specific anatomic sites of cancer. In prepara- In 1976 the AJCC sponsored a National Cancer Conferencetion for each new edition of the AJCC Cancer Staging Manual, on Classification and Staging. The deliberation at this confer-the task forces are convened and serve as consensus panels to ence led directly to the development of the first edition of theAmerican Joint Committee on Cancer • 2010 xiii
  • 12. Cancer Staging Manual, which was published in 1977. With of Surgical Oncology and the British Association of Surgicalthe publication of the first edition, the AJCC broadened its Oncology in London in 1987.scope by recognizing its leadership role in the staging of can- During the 1990s, the importance of TNM staging ofcer for American physicians and registrars. The second edi- cancer in the USA was heightened by the mandatory require-tion of this manual (1983) updated the earlier edition and ment that Commission on Cancer–approved hospitals useincluded additional sites. This edition also served to enhance the AJCC-TNM system as the major language for cancerconformity with the staging espoused by the TNM Commit- reporting. This requirement has stimulated education of alltee of the UICC. physicians and registrars in the use of the TNM system, and The expanding role of the American Joint Committee in credit goes to the Approvals Program of the Commission ona variety of cancer classifications suggested that the original Cancer for this insightful recognition. The AJCC recognizesname was no longer applicable. In June 1980 the new name, that, with this seventh edition of the AJCC Cancer Stagingthe American Joint Committee on Cancer, was selected. Manual, the education of medical students, resident physi-Since the early 1980s, the close collaboration of the AJCC cians, physicians in practice, and cancer registrars is para-and the UICC has resulted in uniform and identical defini- mount. As the twenty-first century unfolds, new methods oftions and stage groupings of cancers for all anatomic sites education will complement the seventh edition of the AJCCso that a universal system is now available. This worldwide Cancer Staging Manual and will ensure that all those whosystem was espoused by Robert V. P. Hutter, M.D., in his care for cancer patients will be trained in the language ofPresidential Address at the combined meeting of the Society cancer staging.xiv American Joint Committee on Cancer • 2010
  • 13. AMERICAN JOINT COMMITTEE ON CANCER AJCCCANCER STAGING MANUAL Seventh Edition