TNM staging and prognosis. Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania

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1 TNM staging and prognosis Alexandru Eniu, MD, PhD Medical Oncologist Department of Breast Tumors Cancer Institute Ion Chiricuţă Cluj-Napoca, Romania

2 The Basics of TNM Staging Premises: Cancers of the same anatomic site and histology share similar patterns of growth and similar outcomes. As the size of the primary tumor (T) increases, regional lymph node involvement (N) and/or distant metastases (M) become more likely.

3 Diagnosis THE ONLY CERTITUDE = PATHOLOGY Always necessary Insufficient for planning treatment We need prognostic factors predictive factors targeted diagnosis

4 The Basics of TNM Staging TNM records the 3 significant events in the life history of a cancer: Local Tumor Growth (T) TX, Tis, T0, T1, T2, T3, T4 Spread to Regional Lymph Nodes (N) NX, N0, N1, N2, N3 Distant Metastasis (M) MX, M0, M1

5 The Basics of TNM Staging Stage Grouping After assignment of TNM categories Stage 0, I, II, III or IV Multiple Simultaneous Tumors The tumor with the highest T category is the one selected for classification and staging Simultaneous bilateral cancers in paired organs are staged separately Staging of primary unknown tumors can be based on clinical suspicion of the primary origin

6 Why Use TNM? Allows the health professional to determine appropriate treatment ( primary, adjuvant) Allows assessment of prognosis and outcomes Enables the reliable evaluation of treatment results Results in quality cancer care Enables comparison of results

7 Primary Tumor (T) Same definitions for clinical and pathologic T If the measurement is made by physical examination, the examiner will use the major headings (T1, T2, or T3). If mammographic or pathologic measurements are used, the subsets of T1 can be used. Tumors should be measured to the nearest 0.1 cm increment. TX T0 Tis Primary tumor cannot be assessed No evidence of primary tumor Carcinoma in situ (DCIS, LCIS, Paget s) Note: Paget s disease associated with a tumor is classified according to the size of the tumor.

8 T1 Tumor 2 cm or less in greatest dimension

9 Primary Tumor (T) Subdivisions of T1 T1 Tumor 2 cm or less in greatest dim. T1mic T1a T1b T1c Microinvasion 0.1 cm or less in greatest dimension Tumor more than 0.1 cm but not more than 0.5 cm in greatest dimension Tumor more than 0.5 cm but not more than 1 cm in greatest dimension Tumor more than 1 cm but not more than 2 cm in greatest dimension

10 T2 Tumor more than 2 cm but not more than 5 cm in greatest dimension

11 T3 Tumor more than 5 cm in greatest dimension

12 T4 Tumor of any size with direct extension to (a) chest wall or (b) skin T4a Extension to chest wall, not including pectoralis muscle T4b Edema (including peau d orange) or ulceration of the skin of the breast, or satellite skin nodules confined to the same breast T4c T4d Both T4a and T4b Inflammatory carcinoma

13 Inflammatory carcinoma vs neglected T4b T4d T4d T4b

14 Regional Lymph Nodes (N) Clinical NX Regional lymph nodes cannot be assessed (e.g., previously removed) N0 No regional lymph node metastasis N1 Metastasis to movable ipsilateral axillary lymph node(s) N2 Metastases in ipsilateral axillary lymph nodes fixed or matted, or in clinically apparent* ipsilateral internal mammary nodes in the absence of clinically evident axillary lymph node metastasis N2a Metastasis in ipsilateral axillary lymph nodes fixed to one another (matted) or to other structures N2b Metastasis only in clinically apparent* ipsilateral internal mammary nodes and in the absence of clinically evident axillary lymph node metastasis Clinically apparent is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination or grossly visible pathologically.

15 Regional Lymph Nodes (N) Clinical N3 Metastasis in ipsilateral infraclavicular lymph node(s) with or without axillary lymph node involvement, or in clinically apparent* ipsilateral internal mammary lymph node(s) and in the presence of clinically evident axillary lymph node metastasis; or metastasis in ipsilateral supraclavicular lymph node(s) with or without axillary or internal mammary lymph node involvement N3a node(s) Metastasis in ipsilateral infraclavicular lymph N3b Metastasis in ipsilateral internal mammary lymph node(s) and axillary lymph node(s) N3c Metastasis in ipsilateral supraclavicular lymph node(s) *Clinically apparent is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination or grossly visible pathologically.

16 Regional Lymph Nodes (N) Pathologic (pn) pnx Regional lymph nodes cannot be assessed (e.g., previously removed, or not removed for pathologic study) pn0 No regional lymph node metastasis histologically, no additional examination for isolated tumor cells (ITC) pn1 Metastasis in 1 to 3 axillary lymph nodes, and/or in internal mammary nodes with microscopic disease etected by sentinel lymph node dissection but not clinically apparent** pn2 Metastasis in 4 to 9 axillary lymph nodes, or in clinically apparent* internal mammary lymph nodes in the absence of axillary lymph node metastasis pn3 Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent* ipsilateral internal mammary lymph nodes; or in ipsilateral supraclavicular lymph nodes

17 Distant Metastasis (M) MX Distant metastasis cannot be assessed M0 No distant metastasis M1 Distant metastasis

18 Breast Cancer Staging Stage I Stage 1 N0 T1

19 Stage IIa may also describe cancer in the axillary lymph nodes with no evidence of a tumor in the breast Breast Cancer Staging Stage IIA Stage IIA N1 T1 N1 N0 T2

20 Breast Cancer Staging Stage IIB Stage IIB N1 T2 N1 N0 T3

21 Breast Cancer Staging Stage IIIA Stage IIIA N1 T3 N1 N2 T1-3 N2 T1-3

22 Breast Cancer Staging Stage IIIB, IIIC Stage IIIB N0 T4 N1 T4 N1 Stage IIIC N3 N2 T4 N2

23 Stage IV Breast Cancer Stage IV breast cancer can be any size and has spread to distant sites in the body, usually the bones, lungs or liver, or chest wall

24 AJCC Staging System (anatomic) T N M Stage I IIa IIb IIIa 4 or IIIb Any 3 0 IIIc any any 1 IV

25

26 Survival in relation to presence and extent of regional LNs

27 Breast Cancer Survival Rates Stage 2yr 5yr% 10yr% %BC I II III IV (MBC) <1 10 The overall median survival for MBC is <2ys. 50% of women with MBC stage IV will live <2ys.

28 How to Implement AJCC TNM Staging Development of policy and procedure Staging form part of the medical record Development of a process by which the staging form is placed in the medical record Size of facility and number of analytic cases Pathology, medical records, cancer registry Development of Quality Control Methods to assure compliance

29 The TNM is imperfect! Prognostic factors Lymph Node Involvement Tumor Size Tumor Grade Lymphatic/Vascular/Perineural Invasion Age of the patient Tumor biology Profile * ER, PR *Her2neu expression *Ki 67/ proliferation fraction

30 Future of Oncology Diagnostic: Organ Molecular Etiology Classification: Histology Molecular Function Focus: Therapy Prevention Therapy: Toxic, Complex Non-Toxic, Targeted Outcome prediction: Suboptimal Precise Patients follow-up : Anatomic Systemic

31 Backup slides

32 Regional Lymph Nodes (N) Pathologic (pn) a pn0(i ) pn0(i+) cluster No regional lymph node metastasis histologically, negative IHC No regional lymph node metastasis histologically, positive IHC, no IHC greater than 0.2 mm pn0(mol ) No regional lymph node metastasis histologically, negative molecular findings (RT PCR) b pn0(mol+) No regional lymph node metastasis histologically, positive molecular findings (RT PCR) b

33 Regional Lymph Nodes (N) a Classification is based on axillary lymph node dissection with or without sentinel lymph node dissection. Classification based solely on sentinel lymph node dissection without subsequent axillary lymph node dissection is designated (sn) for sentinel node, e.g., pn0(i+) (sn). b RT-PCR: reverse transcriptase/polymerase chain reaction.

34 Regional Lymph Nodes (N) pn1 pn1mi pn1a pn1b pn1c Metastasis in 1 to 3 axillary lymph nodes, and/or in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent** Micrometastasis (greater than 0.2 mm, none greater than 2.0 mm) Metastasis in 1 to 3 axillary lymph nodes Metastasis in internal mammary nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent** Metastasis in 1 to 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent.** (If associated with greater than 3 positive axillary lymph nodes, the internal mammary nodes are classified as pn3b to reflect increased tumor burden)

35 Regional Lymph Nodes (N) Pathologic (pn) a pn2 nodes, or in mammary lymph axillary lymph node pn2a least pn2b Metastasis in 4 to 9 axillary lymph clinically apparent* internal nodes in the absence of metastasis Metastasis in 4 to 9 axillary lymph nodes (at one tumor deposit greater than 2.0 mm) Metastasis in clinically apparent* internal mammary lymph nodes in the absence of axillary lymph node metastasis pn3 Metastasis in 10 or more axillary lymph nodes, or in infraclavicular lymph nodes, or in clinically apparent* ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes with clinically negative microscopic metastasis in internal mammary lymph nodes; or

36 Regional Lymph Nodes (N) Pathologic (pn) a pn3a Metastasis in 10 or more axillary lymph nodes (at least one tumor deposit greater than 2.0 mm), or metastasis to the infraclavicular lymph nodes pn3b Metastasis in clinically apparent* ipsilateral internal mammary lymph nodes in the presence of 1 or more positive axillary lymph nodes; or in more than 3 axillary lymph nodes and in internal mammary lymph nodes with microscopic disease detected by sentinel lymph node dissection but not clinically apparent** pn3c Metastasis in ipsilateral supraclavicular lymph nodes *Clinically apparent is defined as detected by imaging studies (excluding lymphoscintigraphy) or by clinical examination.

37 Stage Grouping Stage 0 Tis N0 M0 Stage I T1* N0 M0 Stage IIA T0 N1 M0 T1* N1 M0 T2 N0 M0 Stage IIB T2 N1 M0 T3 N0 M0 Stage IIIA T0 N2 M0 T1* N2 M0 T2 N2 M0 T3 N1 M0 T3 N2 M0 Stage IIIB T4 N0 M0 T4 N1 M0 T4 N2 M0 Stage IIIC Any T N3 M0 Stage IV Any T Any N M1 Note: Stage designation may be changed if post-surgical imaging studies reveal the presence of distant metastases, provided that the studies are carried out within 4 months of diagnosis in the absence of disease progression and provided that the patient has not received neoadjuvant therapy.

38 Schematic Diagram of Breast and Regional Lymph Nodes AJCC Cancer Staging Atlas

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