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AJCC Cancer Staging 8 th Edition Alexander B. Olawaiye, MD University of Pittsburgh Validating science. Improving patient care. No materials in this presentation maybe repurposed without the Cancer. Permission request maybe submitted at cancerstaging.org. Historical Perspective Staging based on the TNM concept was first championed by Dr. Pierre Denoix a surgical oncologist from Insitut Gustave- Roussy, Paris (1943-52) cancerstaging.org 1

Historical Perspective North American effort first organized as the American Joint Committee for Cancer Staging and End Results Reporting (AJC) (1959) American College of Surgeons, American College of Radiology, College of American Pathologists, College of Physicians, American Cancer Society & the National Cancer Institute AJC (1970) adopted objectives, rules & regulations of the AJC resulted in formulation and publication of systems of classification of cancer First Edition of AJC staging manual published just 40 years ago, in 1977 Manual for Staging of Cancer (1977), American Joint Committee for Cancer Staging & End Result Reporting, 1st Edition Philosophy of staging by the TNM system : It is intended to provide a way by which designation for the state of a cancer at various points in time can be readily communicated to others to assist in decisions regarding treatment and to be a factor in judgment as to prognosis. Ultimately, it provides a mechanism for comparing like or unlike groups of cases, particularly in regard to the results of different therapeutic procedures cancerstaging.org 2

Subsequent Staging Manuals June 1980, the new name American Joint Committee on Cancer AJCC was selected and the decision for uniformity with identical definitions with the UICC was adopted 2nd Edition,1983 Additional sites added, conceded that several recommendations are preliminary, consistency with TNM UICC staging system 3rd Edition, 1988 1990 s importance heightened by the mandatory requirement by Commission on Cancer approved hospital use of AJCC-TNM system as the major language of cancer reporting stimulated education of physicians & registrars with widespread use 4th Edition, 1992 5th Edition, 1997 6th Edition, 2002 judicious transition of non anatomic factors that modified stage groups AJCC Cancer Staging Manual, 7th Edition 2010 Roles: Communication Standardized nomenclature of cancer (doctor to patient, doctor to doctor) Clinical practice Staging & prognosis Treatment recommendations Clinical trials Eligibility Stratification Research at all levels Reporting population science Longitudinal cancer instance Changing spectrum of disease Efficacy of treatment Quality of care cancerstaging.org 3

Persistent Challenges to TNM Staging TNM largely limited to anatomic information Lacks biologic data and impact of response Creates bins of like patients TNM does not always meet needs of clinicians and patients is it still relevant Individualized prognosis Predict value of therapy TNM risks marginalization Should TNM maintain anatomic base Population incidence and impact Longitudinal changes World wide use What s Changing Since the Last Edition - The Evolving Landscape (2008-2013..) Advances in molecular underpinnings of cancer - TCGA etc. - oncogenesis, progression, resistance molecular classification of cancer Increasing availability of high throughput testing, mutational analysis (sequencing), microarrays (RNA, mi RNAs, SNPs, etc) Advances in informatics & computational biology; increased adoption of EHRs, data interoperability, real time risk calculating strategy apps (nomograms, tables, etc) Cancer care is increasingly coordinated through well defined clinical multidisciplinary teams Maturing data is gradually becoming available on prognostic and predictive factors that may allow evidence-based decision making Surgical, medical (targeted) and radiation oncology therapies that continue to become more sophisticated; as are diagnostic modalities (imaging and pathology) Globalization of cancer universal applicability of treatment & molecular advances cancerstaging.org 4

AJCC Cancer Staging Manual Editions Edition Publication Effective dates for cancer diagnoses 1 st 1977 1978 1983 (6 years) 2 nd 1983 1984 1988 (5 years) 3 rd 1988 1989 1992 (4 years) 4 th 1992 1993 1997 (5 years) 5 th 1997 1998 2002 (5 years) 6 th 2002 2003 2009 (7 years) 7 th 2009 2010 2017 (8 years) Average 5.7 years The 8 th Edition cancerstaging.org 5

The 8 th Edition Online Content: Set for Rolling Updates Staging forms Supplementary Online Resources: Application Programming Interface (API) for software and app developers Risk Assessment Models Emerging Factors for Clinical Care Recommendations for Clinical Trial Stratification Illustrations References www.cancerstaging.org AJCC Cancer Staging Manual Editions 3-Year Project 57 Chapters 16 Task Forces 266 individuals from o 5 continents o 11 countries 3-Year Project 83 Chapters 18 Expert Panels + 7 Cores 434 individuals from o 6 continents o 23 countries o 188 institutions cancerstaging.org 6

Release of 8th Edition Cancer Staging Manual released on October 6th, 2016 8th Edition effective with cases diagnosed January 1, 2018 Print copies can be ordered through Springer.com Updates Updated staging systems in several chapters Updated content in each chapter Updated and more illustrations (manual and atlas in one) Updated histologic classifications and grading systems Updated WHO/IARC histology codes cancerstaging.org 7

Assigning Stage: The Role of the Managing Physician Staging requires the collaborative effort of many professionals, including the managing physician, pathologist, radiologist, cancer registrar and others While the pathologist and the radiologist provide important staging information, and may provide important T-, N-, and/or M-related information, stage is defined ultimately from the synthesis of an array of patient history and physical examination findings supplemented by imaging and pathology data Only the managing physician can assign the patient s stage, since only (s) he routinely has access to all of the pertinent information from the physical exam, imaging studies, biopsies, diagnostic procedures, surgical findings, and pathology reports New Feature: Evidence Based Approach Levels of evidence defined by EBM & Statistics core for key information ensure transparency Changes to stage definitions based on data - no changes to stage definition based on level 4 evidence Data sources for stage definition changes and 8E content NCDB SEER Multi-institutional databases International databases (Lung, Melanoma, Esophagus ) Publications cancerstaging.org 8

New Feature: Imaging Core & Section in each chapter Consistent and broad overview of applications of imaging in staging in each chapter Provides guidance to physicians when ordering tests Several imaging section chapters describe what imaging tests are most appropriate for assessing tumor stage information the temporal order in which the appropriate imaging tests are typically performed the specific T, N, and M information that can be extracted from imaging tests for the cancer Several chapters - information for radiologists on reporting results - Structured reporting is promoted - Links or references to disease- or specialty-specific society guidelines New Features: Precision Medicine Vision Prognostic factors Required for prognostic stage grouping Recommended for clinical care Emerging factors (online only) Risk Assessment Models for select cancer sites Recommendations for Clinical Trial Stratification cancerstaging.org 9

Direction of Cancer Staging Renewed AJCC Vision cancerstaging.org 10

Color Coding AJCC & FIGO First rules of female genital tract cancer staging was published in 1929 by the League of Nations. This rules evolved into the staging system developed and regularly updated by FIGO. In 1976, AJCC accepted the FIGO stage grouping for gynecologic cancers. Gynecologic cancer staging in all editions of the AJCC staging manual have been closely aligned with FIGO staging. 22 cancerstaging.org 11

FIGO Staging publication timelines 1988: FIGO staging for all gynecologic cancers updated 2009: FIGO staging for carcinoma of the vulva, cervix and endometrium. 2009: FIGO staging for uterine sarcoma. 2014: FIGO s staging classification for cancer of the ovary, fallopian tube, and peritoneum: abridged republication. 2009: AJCC 7 th Edition Cancer Staging Manual 23 Updates in : pn0(i+) Metastatic cancer to lymph node(s) fall into one of 3 categories based on the size of metastasis; (1) Individual Tumor Cells (ITC) -- <0.2mm (2) Micrometastasis 0.2mm 2mm (3) Macrometastasis -- > 2mm ITC & Micromestasis are jointly referred to as low volume metastasis (LVM). Micro & macrometastasis are both classified as N1 The 8 th Edition encourages documentation of pn0(i+), which will not currently change the stage grouping or FIGO stage but will be a helpful data to analyze in future. 24 cancerstaging.org 12

Updates in : Vulva Melanoma has been removed from this chapter Melanoma should be staged according to the classification of skin melanoma (chapter 47) (I) Classification of p16 status should be collected if obtained (III) Full length of histologic subtypes according to the WHO classification of tumors is included A chapter on imaging is embedded with suggestions on how to document image findings 25 Updates in : Vulva Illustrations of the T, N and M categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. Perineal lesions can be challenging to classify and the 8 th edition offers the following recommendations; Lesions clearly arising from the vulvar and spreads to the perineum/anus should be classified as vulvar. Lesions clearly arising from the anus but extends to the perineum should be classified as perianal. Perineal lesions that do not clearly arise from the anus or vulvar, clinician should denote exact location and favored impression regarding classification e.g. perineum favor vulva or perineum favor anus. 26 cancerstaging.org 13

Updates in : Vulva There are only 4 categories of grading (Gx, G1, G2, and G3). Grade 4 has been removed. 27 Updates in : Vagina Mucosal melanoma of the vagina is not included in this edition of AJCC staging system. T1a ( 2cm) and T1b (>2cm) subcategories were added. Both are FIGO stage I. Similarly, T2a ( 2cm) and T2b (>2cm) subcategories were added. Both are FIGO stage II. These additions were made to distinguish a tumor size cutoff of 2 cm for prospective data collection for studying prognostic significance. (III) 28 cancerstaging.org 14

Updates in : Vagina Full length of histologic subtypes according to the WHO classification of tumors is included. A chapter on imaging is embedded with suggestions on how to document image findings. There are only 4 categories of grading (Gx, G1, G2, and G3). Grade 4 has been removed. Kaplan-Meier curves by stage and tumor size (OS) from a large SEER data analysis are included. Illustrations of the T and N categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. 29 Updates in : Cervix N1 has been removed from FIGO stage IIIB Involvement of para-aortic lymph nodes removed from the definition of M1 30 cancerstaging.org 15

Updates in : Cervix Full length of histologic subtypes according to the WHO classification of tumors is included. ***A chapter on imaging is embedded with suggestions on how to document image findings. Cervix was the strongest motivation for this chapter*** There are only 4 categories of grading (Gx, G1, G2, and G3). Grade 4 has been removed. Illustrations of the T and N categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. 31 Updates in : Corpus Leiomyosarcomas, endometrial stromal sarcomas and adenosarcomas now have a separate chapter called corpus uteri-sarcoma (chapter 54). Stage 0 and Tis have been removed. Endometrial intraepithelial carcinoma (EIC) should be considered a T1 cancer. Histologic Grade 4 has been removed, should be considered Grade 3. Lymph node micometastasis (<2mm) to be reported as N1mi (pelvis) and N2mi (para-aortic). 32 cancerstaging.org 16

Updates in : Corpus Full length of histologic subtypes according to the WHO classification of tumors is included. A chapter on imaging is embedded with suggestions on how to document image findings. There are only 4 categories of grading (Gx, G1, G2, and G3). Grade 4 has been removed. Illustrations of the T and N categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. 33 Updates in : Corpus uterisarcoma This is a new chapter Full length of histologic subtypes according to the WHO classification of tumors is included. Uterine carcinosarcoma has been removed from sarcoma and now staged with the other corpus epithelial cancers. There are only 4 categories of grading (Gx, G1, G2, and G3). Grade 4 has been removed. Illustrations of the T and N categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. 34 cancerstaging.org 17

Updates in : Corpus uterisarcoma In alignment with FIGO, leiomyosarcoma and endometrial stromal sarcoma are similarly staged. Adenosarcoma is separately staged Grade is not a collected element in leiomyosarcoma, as all are high grade tumors. 35 Updates in : Corpus uterisarcoma Sarcomas and related tumors involving peritoneum or visceral organs represent an area of overlap between the soft tissue sarcoma chapters and gynecology chapters. The affected histologies include; 8810 Adult fibrosarcoma 8815 Solitary fibrous tumor 8825 Inflammatory myofibroblastic sarcoma 8890 Leiomyosarcoma - named leiomyomatosis peritonealis disseminate in GYN chapter with borderline behavior 8936 Gastrointestinal stromal tumor also called extragastrointestinal stromal tumor in GYN chapter Such staging should be deferred to the relevant soft tissue sarcoma chapter, A link is provided in the gyn. chapters 36 cancerstaging.org 18

Updates in : Ovary, Fallopian tube & Primary Peritoneal Carcinoma Fallopian tube now shares the same staging and chapter as ovary and primary peritoneal carcinoma T1C has been split into 3 sub-categories; 1C1= intraoperative tumor rupture, 1C2= tumor rupture before surgery, 1C3= positive peritoneal washing. Former T2C has been eliminated. New N1: retroperitoneal (pelvic or para-aortic) LN spread without extra-pelvic peritoneal involvement. New N1a1(FIGO IIIA1i): LN metastasis up to 5 mm New N1b (FIGO IIIA1ii): : LN metastasis > 5 mm 37 Updates in : Ovary, Fallopian tube & Primary Peritoneal Carcinoma New TIIIA2: Microscopic extra-pelvic peritoneal involvement TIIIB & TIIIC have been modified and both are now based on peritoneal metastasis only regardless of LN status. New: Parenchymal involvement of both liver and spleen is now M1b (FIGO stage IVB). New: Transmural involvement of intestine is now M1b (FIGO stage IVB). 38 cancerstaging.org 19

Updates in : Ovary, Fallopian tube & Primary Peritoneal Carcinoma Full length of histologic subtypes according to the WHO classification of tumors is included. A chapter on imaging is embedded with suggestions on how to document image findings. There are only 5 categories of grading (Gx, GB, G1, G2, and G3). Grade 4 has been removed. Illustrations of the T, N and M categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. 39 Updates in : Gestational Trophoblastic Neoplasms Complete and partial hydatidiform moles have been removed from this chapter. Full length of histologic subtypes according to the WHO classification of tumors is included. A chapter on imaging is embedded with suggestions on how to document image findings. Illustrations of the T and M categories are included therefore an owner of the 8 th edition staging manual doesn t need a separate atlas. 40 cancerstaging.org 20

Thank you! Questions 41 cancerstaging.org 21