Overview of New AJCC Cancer Staging Jason P. Wilson, MD, MBA, FACS Morton Plant Mease Grand Rounds April 3, 2018

No financial disclosures

Updates? https://www.doc-related.com/single-post/2017/02/09/EMR-Upgrades

Objectives Define AJCC and its role in staging Describe the rationale, types, and elements of cancer staging Provide historical perspective on staging Highlight changes to recent guidelines for staging and rationale

The First Question Revisited

The First Question Revisited What is my stage?

Goals of Cancer Staging Describe the amount and severity of cancer Define prognosis based on prior outcomes Aid treatment and clinical trial planning Provide a common lexicon

AJCC American Joint Committee on Cancer Established in 1959 Works with the Union for International Cancer Control (UICC) To develop, promote, and maintain evidence based systems for classification and management of cancer

AJCC 22 member organizations Surgical Representation Radiology Representation Medical and Radiation Oncology Representation Pathology Representation Managed by the American College of Surgeons

Historical Perspective 1st Edition: 1977 2nd Edition: 1983 3rd Edition: 1988 4th Edition: 1992 5th Edition: 1997 6th Edition: 2002 7th Edition 2009 8th Edition 2016

Historical Perspective Based on data from multiple databases: NCDB: National Cancer Database from Commission on Cancer (70%) ACS/ACS SEER: Surveillance, Epidemiology, and End Results from Nat’l Cancer Institute Other population-based registries

Four Types of Cancer Staging Clinical: based on exam, imaging, and pathology Pathologic: combination of clinical findings and surgical pathology Post-therapy or Post-neoadjuvant therapy: pathologic/clinical staging after treatment; prior to surgery Restaging: the extent of disease in the setting of recurrence

Elements of Staging Location of primary tumor/organ of origin Tumor size/extent - T Lymph node involvement - N Presence or absence of distant metastasis - M Non-anatomic elements Stage is determined by the treating physician

Case 1 55 yo female is seen for routine physical examination by her physician He appreciates a mass in the inner breast Mammogram evaluation confirms a 2.4 cm mass

Case 1

Case 1 Pathology: Invasive Duct Carcinoma Grade 3 Triple Negative (ER-, PR-, HER-2-) Ki-67: 65%

Case 1 Stage: IIA (T2N0M0) Given location seen for neoadjuvant chemotherapy Adriamicin, CytoxanTaxol and Carboplatin Some response clinically

Case 1 Partial mastectomy/Sentinel node Pathology: 3 negative nodes Invasive Carcinoma grade 3 Margins negative ypT2N0cM0 (IIA) Goes on to adjuvant radiation Metastatic disease within 5 months

Case 2 55 yo female presents for screening mammogram with tomosynthesis 3.3 cm mass noted

Case 2

Case 2 Stage: IIA (T2N0M0) ER+, PR+, HER-2- Underwent Lumpectomy/Sentinel Node Pathology: 30 mm cancer, grade II Margins widely negative Two negative Sentinel nodes Tumor Board recommended Genomic profile

Case 2: Genomic profile low risk of recurrence 97.8% chance of being disease free at 5 years only with endocrine therapy

Why?

Subtypes Luminal A (typically hormone+, low proliferation) Luminal B (typically hormone low, high proliferation) Her-2 (her-2 positive cancers) Basal Like (triple negative cancers)

Purpose “First and foremost, staging provides patients with cancer and their physicians the critical benchmark and standards for defining prognosis, the likelihood of overcoming the cancer once diagnosed, and for determining the best treatment approach for the disease.” AJCC 8th edition page ix

Staging Manual 8th Edition Staging guidelines Guidance for ordering tests i.e. what imaging tests and when tests appropriate Provides level of evidence for guidelines

New Staging Systems Cervical Lymph Nodes and Unknown Primary Tumors of H&N Pharynx Cutaneous Squamous Cell of H & N Thymus Bone Sarcoma Parathyroid Leukemia

New Paradigms Human papillomavirus: oropharyngeal staging based on HPV status Separate staging systems for neoadjuvant therapy of esophagus and stomach Bone and sarcoma (separate staging systems based on anatomic sites) Introduction of an H category for heritable cancer trait in retinoblastoma

Breast Cancer Staging From one page table to 5 pages

Breast Cancer Staging Two stage group options Anatomic: where biomarkers not available Prognostic: for use in all U.S.A. patients Inclusion of grade, HER2, ER, PR Inclusion of multigene panels

Breast Cancer Staging Lobular carcinoma in situ removed from Tis 1% or greater stain for ER & PR considered positive HER2 “equivocal” is considered negative

Breast Cancer Staging Multigene panels For use only with ER/PR+, HER2 negative, node negative tumors less than/= 5 cm Mammoprint, Oncotype DX, Endopredict,PAM50, Breast Cancer Index Only low risk scores considered All Stage IA despite size (T)

Prognostic Stage Groups for Breast Based on populations of patients that have been offered and mostly treated with appropriate endocrine and /or systemic therapy 40% of the anatomic stages changed to a different stage based on inclusion of the prognostic factors and grade

Examples of Stage Changes T3 N1-2 M0 Stage III in 7th edition Same TNM with grade 1, triple positive: prognostic stage IB in 8th edition T1 N0 M0 Stage I in 7th edition Same TNM, grade 2, triple negative: prognostic stage IIA in 8th edition As measured by outcomes

Cases Revisited with AJCC 8 Both T2N0M0 Case 1 (2 cm Triple Negative): IIA (Basal type) Case 2 (2 cm Hormone Positive): IA (Luminal A)

Melanoma Important T changes Mitotic rate not long used Melanoma <0.8 without ulceration T1a Melanoma <1.0 with ulceration T1b Melanoma 0.8-1.0 without ulceration T1b

Melanoma Important N changes a=clinically occult b=clinically detected c=microsatellites, satellites and in-transit disease

Case 3 51 yo patient who had a spot on his thigh Started to change while on a cruise Case review showed 1.95 mm melanoma mitotic rate 0-1, no ulceration

Case 3 Wide excision of left leg Sentinel node left groin

Case 3 Pathology: No residual melanoma SLN: 1.5 mm metastasis Stage pT2aN1a cM0 Pathologic IIIA

Melanoma https://www.skincancer.org/publications/the-melanoma-letter/2018-vol-36-no-1/ajcc-staging-system

Melanoma https://www.skincancer.org/publications/the-melanoma-letter/2018-vol-36-no-1/ajcc-staging-system

Melanoma https://www.skincancer.org/publications/the-melanoma-letter/2018-vol-36-no-1/ajcc-staging-system

Changes to Improve Patient Care Sparing some systemic therapy More accurate staging based on prognosis which is really what patients want

Summary Most recent changes to cancer staging took effect January 2018 AJCC is the governing body for standardized cancer staging in USA New staging contains both anatomic and prognostic factors Multiple upstaging/downstaging based on clinical outcomes

For more information AJCC website: Cancerstaging.org

Questions?