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. AJCC
CANCER STAGING
MANUAL
Seventh Edition
AMERICAN JOINT COMMITTEE ON CANCER
Executive Office
633 North Saint Clair Street
Chicago, IL 60611-3211
This manual was prepared and published through the support of the American Cancer Society, the
American College of Surgeons, the American Society of Clinical Oncology, the Centers for
Disease Control and Prevention, and the International Union Against Cancer.
CD-ROM
Included
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 Dedication
This seventh edition of the AJCC Cancer Staging Manual is on Cancer, the National Cancer Registrars Association, and
dedicated 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 to
changes in cancer staging being introduced with this edition patients extends well beyond the AJCC as evidenced by his
are 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 his
Program for Cancer Registries of the CDC, the Commission honor.
American Joint Committee on Cancer • 2010 v
6. Preface
Cancer 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 less
cancer incidence, extent of disease at initial presentation, and common cancers, there are few outcome data available. These
the 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 potentially
trials. 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 for
and 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 to
staging system is a never-ending process. Toward this end, develop new large data sets to provide high-level evidence
the American Joint Committee on Cancer (AJCC) has led to support changes in the staging system. Examples of this
these efforts in the USA since 1959. A collaborative effort include the work in melanoma that led to changes in the sixth
between the AJCC and the International Union for Cancer edition and their refinement in this seventh edition, use of
Control (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 the
anatomic information on the extent of the primary tumor, colorectal staging system, and the use of existing data sets
regional 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 melanoma
of the Committee on Clinical Stage Classification and Applied collaborative, the best examples in refining staging for the
Statistics. 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) and
1977. 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 availability
and the AJCC Cancer Staging Manual. The revision cycle is of biologic factors that predict cancer outcome and response
6–8 years, a time frame that provides for accommodation of to treatment with better accuracy than purely anatomically
advances in cancer care while allowing cancer registry systems based staging. This has led some cancer experts to conclude
to 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 only
volunteer 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 and
and others. These volunteers, representing all relevant disci- structure of staging. Beginning with the sixth edition of the
plines, are organized into disease teams chaired by leading cli- AJCC Cancer Staging Manual, there was judicious addition of
nicians. These teams make recommendations for change in the nonanatomic factors to the classifications that modified stage
staging system based on available evidence supplemented with groups. This shift away from purely anatomic information
expert consensus. Supporting these teams is a panel of expert has been extended in the current edition. Relevant markers
statisticians 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 included
American 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 or
gastrointestinal 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 in
discovery 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 out
ment 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, showed
to maintain the anatomic base to cancer staging. Anatomic the leadership and the vision over a decade ago that led to
extent of disease remains the key prognostic factor in most the development of the Collaborative Stage Data Collection
diseases. 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 extremely
advances in screening and treatment and to be able to apply popular and useful AJCC Cancer Staging Atlas, and did the
stage and compare stage worldwide in situations where new legwork to enhance the collaboration between the UICC
nonanatomic factors are not or cannot be collected. There- and AJCC. The work of our publisher Springer provided the
fore, the staging algorithms in this edition of the AJCC Cancer resources to support this work and the patience needed as
Staging Manual using nonanatomic factors only use them as the Task Forces and editors finished their work. The many
modifiers of anatomic groupings. These factors are not used cancer registrars and the Collaborative Stage Version 2 Work
to define the T, N, and M components, which remain purely Group who worked on the disease teams kept us all properly
anatomic. 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 the
anatomic 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 products
Staging Manual began immediately on publication of the built on this manual, will provide strong support to patients
sixth edition. Under the leadership of the Prognostic Fac- and physicians alike as they face the battle with cancer, and we
tors Task Force of the UICC, an ongoing review of literature hope that it provides the concepts and the foundation for the
relevant to staging was performed and updated annually. A future of cancer staging as we move to the era of personalized
new data collection system that allows capture of nonana- molecular oncology.
tomic information in conjunction with anatomic staging data
was developed and implemented in the USA. A number of
working groups continued data collection and analysis with Stephen B. Edge, Buffalo, NY
the plan to advise AJCC Task Forces. The AJCC provided a David R. Byrd, Seattle, WA
competitive grant program to support work to lead to stag- Carolyn C. Compton, Bethesda, MD
ing revision. An enhanced statistical task force was empan- April G. Fritz, Reno, NV
elled. Finally, in 2006, the disease task forces were convened Frederick L. Greene, Charlotte, NC
to review available evidence and recommend changes to Andy Trotti, Tampa, FL
TNM. After review by the UICC, the changes reflected in this
viii 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 / 629
American Joint Committee on Cancer • 2010 ix
9. Contents
Dedication .....................................................................v 16. Gastrointestinal Stromal Tumor..........................175
Preface ........................................................................ vii 17. Neuroendocrine Tumors .....................................181
Brief Contents by Part .................................................ix
18. Liver (Excluding intrahepatic bile ducts) ..............191
Introduction and Historical Overview ................... xiii
19. Intrahepatic Bile Ducts ........................................201
Part I ...................................................................1 20. Gallbladder ...........................................................211
General Information on Cancer Staging 21. Perihilar Bile Ducts ..............................................219
and 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 .......................241
Part II ................................................................21
Head 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
Skin
Part III .............................................................101
29. Cutaneous Squamous Cell Carcinoma
Digestive System
and Other Cutaneous Carcinomas ......................301
10. Esophagus and Esophagogastric Junction ..........103
30. Merkel Cell Carcinoma ........................................315
11. Stomach ................................................................117
31. Melanoma of the Skin ..........................................325
12. Small Intestine ......................................................127
13. Appendix ..............................................................133
Part VII ............................................................. 345
14. Colon and Rectum ...............................................143 Breast
15. Anus ......................................................................165 32. Breast ....................................................................347
American Joint Committee on Cancer • 2010 xi
10. Part VIII ..........................................................377 Part X ..............................................................521
Gynecologic Sites Ophthalmic Sites
Introduction .......................................................377 48. Carcinoma of the Eyelid ......................................523
33. Vulva .....................................................................379 49. Carcinoma of the Conjunctiva ............................531
34. Vagina ...................................................................387 50. Malignant Melanoma of the Conjunctiva ..........539
35. Cervix Uteri ..........................................................395 51. Malignant Melanoma of the Uvea.......................547
36. Corpus Uteri .........................................................403 52. Retinoblastoma.....................................................561
37. Ovary and Primary Peritoneal 53. Carcinoma of the Lacrimal Gland.......................569
Carcinoma ............................................................419
54. Sarcoma of the Orbit............................................577
38. Fallopian Tube ......................................................429
55. Ocular Adnexal Lymphoma.................................583
39. Gestational Trophoblastic Tumors ......................437
Part XI .............................................................591
Central Nervous System
Part IX .............................................................445 56. Brain and Spinal Cord .........................................593
Genitourinary Sites
40. Penis ......................................................................447 Part XII............................................................599
Lymphoid Neoplasms
41. Prostate .................................................................457
57. Lymphoid Neoplasms (A. Hodgkin and Non-Hodgkin
42. Testis......................................................................469 Lymphomas, B. Primary Cutaneous Lymphomas,
43. Kidney ...................................................................479 C. Multiple Myeloma and Plasma Cell Disorders,
and D. Pediatric Lymphoid Malignancy) .............605
44. Renal Pelvis and Ureter ........................................491
45. Urinary Bladder....................................................497 Part XIII...........................................................629
Personnel and Contributors
46. Urethra ..................................................................507
47. Adrenal..................................................................515 Index ..........................................................................643
xii American Joint Committee on Cancer • 2010
11. Introduction
and Historical Overview
The seventh edition of the AJCC Cancer Staging Manual is review scholarly material related to cancer staging and make
a compendium of all currently available information on the recommendations to the AJCC regarding potential changes in
staging 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 of
staging 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 Association
has been made possible by the mutual respect and diligence of American Cancer Institutes, the National Cancer Registrars
of 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 Society
treatment 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), Irvin
that 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 cancer
Results 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 International
cal profession. The founding organizations of the AJCC are Congress of Radiology (1953), and the International Union
the American College of Surgeons, the American College of Against Cancer (UICC). The latter organization became most
Radiology, the College of American Pathologists, the Ameri- active in the field through its Committee on Clinical Stage
can College of Physicians, the American Cancer Society, and Classification and Applied Statistics (1954). This committee
the National Cancer Institute. The governance of the AJCC is was later known as the UICC TNM Committee, which now
overseen 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 the
for 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 of
tor of the AJCC. Fostering the work of the AJCC has been cancer was utilized as a guide for treatment and prognosis
undertaken 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 Conference
tion 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 the
American Joint Committee on Cancer • 2010 xiii
12. Cancer Staging Manual, which was published in 1977. With of Surgical Oncology and the British Association of Surgical
the 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 of
cer 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 use
included additional sites. This edition also served to enhance the AJCC-TNM system as the major language for cancer
conformity with the staging espoused by the TNM Commit- reporting. This requirement has stimulated education of all
tee 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 on
a variety of cancer classifications suggested that the original Cancer for this insightful recognition. The AJCC recognizes
name was no longer applicable. In June 1980 the new name, that, with this seventh edition of the AJCC Cancer Staging
the 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 of
tions and stage groupings of cancers for all anatomic sites education will complement the seventh edition of the AJCC
so that a universal system is now available. This worldwide Cancer Staging Manual and will ensure that all those who
system was espoused by Robert V. P. Hutter, M.D., in his care for cancer patients will be trained in the language of
Presidential Address at the combined meeting of the Society cancer staging.
xiv American Joint Committee on Cancer • 2010
