Staging System of Cancer How & Why ?

Dr. K.S. Gopinath M.S (Bom), M.A.M.S., F.I.C.S.
Consultant Surgical Oncologist,
Bangalore Institute of Oncology & Mallya Hospital,
Bangalore

Cancer is a multifactorial disease. The last century has witnessed various changes in understanding of cancer from the natural history of cancer, biological behavior, molecular changes and advances in diagnosis and treatment of cancer. Last three decades have witnessed a changing scenario from radical ablative surgery to organ preservation procedures, and a revolution in the form of multi-modality of treatment. All these advances are better understood in the ‘breast cancer model’ wherein therapies have switched from Halstedian concept, to Fisher’s hypothesis, development of identification of BRCA I & II and the clinical utility of Neoadjuvant chemotherapy in LABC.

In the modern era of evidence based medical practice, there is a need to understand staging system of cancers, classify them and to utilize them for therapeutic strategies.

In the past, we have had Manchester classification, Columbia classification, NWTS staging system for staging. Many of these staging systems were controversial, subjective and at times would lead to improper and inadequate documentation. Because of non-uniform assessment and documentation, there was a need for common staging system, which could be followed all over the world that gave birth to “TNM Staging System”.

History of TNM System

Pierre Denoix of France developed TNM system for the classification of malignant tumors during 1943 - 1952. In 1950, UICC appointed a committee on tumor nomenclature and statistics. In 1954, Research commission of UICC set up a special committee on clinical stage classification and applied statistics. Since then all the countries, cancer committees met and formulated TNM classification of malignant tumors. The UICC recognized the need for stability in the TNM Classification, so that data can be accumulated in an orderly manner and all oncologists can speak the language in comparing their clinical material and assessing the results of treatment.

PRINCIPLES OF THE TNM SYSTEM

The continuing objectives of UICC are to achieve a common consent in the classification of anatomical extent of the disease.

The stage of the disease at the time of diagnosis may be a reflection of not only of the rate of growth and extension of the neoplasm, but also the type of tumour and the tumor host relationship.

The UICC believes that recording of accurate information on the extent of disease for each site, precise clinical description of tumor and histopathological classification will serve as a guide to staging system.

The main objectives are:

(1) To aid the clinician in the planning of treatment.

(2) To give some indication of prognosis.

(3) To assist in evaluation of results of treatment.

(4) To facilitate the exchange of information between treatment centers.

(5) To contribute to the continuing investigation of human cancers.

The TNM system describes the anatomical extent of the disease, is based on three components-

T- The extent of primary tumor- Tx, T0, T1, 2,3,4

N- Presence or absence of regional lymph nodes- N0, N1, 2,3

M- Presence or absence of distant metastases- M0, M1 Classification

Clinical Classification:

TNM- CTNM It is a pretreatment staging system. This is based on evidence acquired before treatment. Such evidence arises from physical examination, imaging, endoscopies, surgical exploration and other relevant examination.

The following general definitions are used throughout:

T- Primary Tumor

N- Regional Lymph Nodes

M- Distant Metastasis

The category M1 may be further specified according to the following notation:

Pulmonary	PUL (C34)
Osseous	OSS(C40, 41)
Hepatic	HEP (C22)
Brain	BRA(C71)
Lymph nodes	LYM(C77)
Bone marrow	MAR( C42.1)
Pleura	PLE (C38.1,2)
Peritoneum	PER (C48.1,2)
Adrenals	ADR (C74)
Skin	SKI (C44)
Others	OTH

Subdivisions of TNM

Subdivisions of some main categories are available for those who need greater specificity (e,g., T1a, 1b or N2a, 2b).

Pathological classification- PTNM.

This is post surgical histopathological classification. This is modified form of CTNM taking into consideration, pathological assessment of primary tumor and assesses the regional nodal status, a predictor of prognostification.

PTNM Pathological Classification

The following general definitions are used throughout:

PT- Primary Tumour

PN- Regional Lymph Nodes

PM- Distant Metastasis

The category pM1 may be further specified in the same way as M1. Subdivisions of pTNM

Subdivisions of some main categories are available for those who need greater specificity (e.g., pT1a, 1b or pN2a, 2b).

Histopathological grading

In most sites further information regarding the primary tumour may be recorded under the following heading:

G- Histopathological grading

Additional Descriptors

For identification of special cases in the TNM or pTNM classification, the y, r, a, and m symbols are used. Although they do not affect the stage grouping, they indicate cases needing separate analysis.

‘y’ symbol. In those cases in which classification is performed during or following initial multimodality therapy, the TNM or pTNM categories are identified by a ‘y’ prefix.

‘r’ symbol. Recurrent tumours, when staged after a disease-free interval, are identified by the prefix ‘r’.

‘a’ symbol. The prefix ‘a’ indicates that classification is the first determined at autopsy.

‘m’ symbol. The suffix ‘m’, in parentheses, is used to indicate the presence of multiple primary tambours at a single site.

Optional Descriptors

L- Lymphatic Invasion

V- Venous Invasion

C- Factor

The C-factor, or certainty factor, reflects the validity of classification according to the diagnostic methods employed. Its use is optional.

The C-factor definitions are:

The TNM clinical classification is therefore equivalent to C1, C2, and C3 in varying degrees of certainty, while the pTNM pathological classification generally is equivalent to C4.

Residual Tumour (R) Classification

The absence or presence of residual tumour after treatment is described by the symbol ‘R’. Its use is optional.

TNM and pTNM describe the anatomical extent of cancer in general without considering treatment. They can be supplemented by the R classification, which deals with tumour status after treatment. It reflects the effects of therapy; influences further therapeutic procedures and is a strong predictor of prognosis.

The definitions of the R categories are:

Rx: Presence of residual tumour cannot be assessed
R0: No residual tumour
R1: Microscopic residual tumour
R2: Macroscopic residual tumour

Stage Grouping

Classification by the TNM system achieves reasonably precise description and recording of the apparent anatomical extent of disease. A tumour with four degrees of T, three degrees of N, and two degrees of M will have 24 TNM categories

For purposes of tabulation and analysis, except in very large series, it is necessary to condense these categories into a convenient number of TNM stage groups.

Carcinoma in situ is categorized stage0: cases with distant metastasis stage IV. The grouping adopted is such as to ensure, as far as possible, that each group is more or less homogeneous in respect of survival, and that the survival rates of these groups for each cancer site are distinctive.

For pathological stage grouping, if sufficient tissue has been removed for pathologic examination to evaluate the highest T and N categories, M1 may either clinical (cM1) or pathologic (pM1). However, if only a distant metastasis has had microscopic confirmation, the classification is pathologic (pM1) and the stage is pathologic.

TNM Classification of some common cancers-

Cancer of Oral Cavity

T- Primary tumour

Tx: Primary tumour cannot be assessed
T0: No evidence of primary tumour
Tis: Carcinoma in situ
T1: Tumor 2cm or less in greatest dimension
T2: Tumor more than 2cm but not more than 4cm in greatest dimension
T3: Tumor more than 4cm in greatest dimension
T4: Tumor invades adjacent structures, eg., involving the adjacent muscle, bone, skin

N- Regional Lymph Nodes

Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single ipsilateral lymph node, 3cm or less in greatest dimension
N2: Metastasis in a single ipsilateral lymph node, more than 3cm but not more than 6cm in greatest dimension; or in multiple ipsilateral lymph nodes, none more tan 6cm in greatest dimension; or in bilateral or contra lateral lymph nodes, none more than 6cm in greatest dimension
N2a: Metastasis in a single ipsilateral lymph node more than 3cm but not more than 6 cm in greatest dimension
N2b: Metastasis in multiple ipsilateral lymph nodes, none more than 6cm in greatest dimension
N2c: Metastasis in bilateral or contra lateral lymph nodes, none > 6cm in greatest dimension
N3: Metastasis in a lymph node more than 6cm in greatest dimension

M- Distant Metastasis

Cancer of Penis

Tx: Primary tumour cannot be assessed
T0: No evidence of primary tumour
Tis : Carcinoma in situ
Ta : Nonivasive verrucuous carcinoma
T1 : Tumor invades subepithelial connective tissue
T2 : Tumor invades corpus spongiosum or cavernosum
T3 : Tumor invades urethra or prostate
T4 : Tumor invades other adjacent structures
Nx: Regional lymph nodes cannot be assessed
N0: No regional lymph node metastasis
N1: Metastasis in a single superficial inguinal lymph node
N2: Metastasis in multiple or bilateral superficial inguinal lymph nodes
N3: Metastasis in deep inguinal or pelvic lymph node(s), unilateral or bilateral
Mx: Distant metastasis cannot be assessed
M0: No distant metastasis
M1: Distant metastasis

Cancer Breast

Primary tumour

(T) T0: No demonstrable tumor in breast
Tis: Noninvasive carcinoma in situ or Paget’s disease of the nipple
T1: Greatest dimension: <_ 2cm

T1mic <0.1 cm
T1a> 0.1 <0.5cm
T1b >0.5 <_1cm
T1c >1.0 <_ 2cm

T2: Greatest dimension >2cm and <_5cm
T3: Greatest dimension >5cm
T4: Any size with c:

Lymph nodes (N)

Nx: LAN unknown N0
: LAN negative
N1: LAN positive but not fixed
N1a: None >0.2cm N1b: any >0.2cm
N2: LAN positive and fixed
N3: Ipsilateral internal mammary,

Any status
Metastases (M)

Mx: Distant metastases cannot be assessed
M0: No distant metastasis
M1: Present

UICC & TNM staging system are now used all over the globe to speak a common language. There is alternate stagings system with the modification of the existing system. The AJCC (American Joint Committee on Cancer) is another staging system. The Japanese staging system differs from the other system, where in depth of infiltration is taken into consideration and WTNM is the staging system used especially for cancer of the esophagus, EGC (Early Gastric Cancer), where mucosal lesion and depth are very important. The other staging system, which is used, is NWTS

NWTS - (National Wilm’s tumor Study Group). At present V NWTS group staging system is used.

IRS - (Inter Rhabdomyosarcoma Study group is used for RMS in children). This is the post-surgical system.

GTNM - for soft tissue sarcoma

UTNM - with the use of endosonography. There is a changing trend in staging system, used especially for rectal cancer.

Jackson’s Staging system forCancer Penis

Duke’s Staging system for colorectal cancer

Fallacies of TNM System

With the above staging system UICC is trying to bring in uniformity by popularizing TNM system, which denotes the chronological age and only the anatomical loco regional and distant mets. But there are various disadvantages of the system. With the better understanding of the natural history of disease, molecular biology, availability of prognostic factors, all the parameters cannot be incorporated into the present system. The tumor markers and its significance are not included.

The T only denotes the size of the tumour, but factors like depth of infiltration of tumour, vascular invasion, perineural infiltration are not incorporated.

N - denotes the nodal involvement, but number of nodes involved, capsular infiltration, and perinodal involvement are not included. Sentinel node in various organs are not included.

The classification of the patient into high; intermediate and low risk, which is usually used in treatment planning, is not included in the TNM staging system.

Though TNM staging of UICC is an accepted staging system, it has its fallacies and still there is a scope for modification of the staging system to incorporate the clinical finding, utilization of Histopathology, prognostic factor and to include various risk factors, tumour markers etc.

Conclusions:

TNM is the most widely used system for classifying the extent of cancer spread. It is the standard staging system, very popular and universally accepted and brings in uniformity to clinical staging system. It tells us about a chronological age of the tumor, which helps in assessing the prognoses.

References:

UICC- TNM. Fifth Edition