Staging of Malignant Diseases and its Significance

Dr. Tejpal Sharma, Junior Resident; Dr. Ashok Kumar Chauhan Reader; Dr. K.K. Manocha Reader in Radiation Physics, RSO all from Department of Radiotherapy, Pt. B.D.Sharma, PGIMS, Rohtak, Haryana, India.

The staging of cancer is the classification of the disease in terms of extent, progression and severity so that generalizations can be made about prognosis & the choice of therapy. From an operational point of view, staging is 'the procedure of assigning a simple code designator to a patient in accordance with an established set of rules' (Mountain et al. 1974). The axis of classification most useful for predicting outcome & selecting the mode of therapy is the anatomical extent of disease at the time of diagnosis.

The staging of cancers by anatomical extent dates from the beginning of the 20th century when C.F. Steinthal, in 1905, introduced a clinical staging of breast cancer. Later on in 1940, Paterson developed the refined clinical staging system for breast cancer known as the Manchester classification and Haagersen & Stout (1943) developed the Columbia clinical classification.

In 1930, Cuthbert Dukes introduced a pathological stage classification for rectal carcinoma based on the local spread of the primary tumour & the regional lymph node status. It was later on applied to carcinoma of colon also (1945). The Dukes system was repeatedly modified, leading to considerable confusion (Kyriakos 1985) and is replaced by the current AJCC (American Joint Committee on cancer)/UICC (Union Internationale Contre le Cancer) TNM classification.

Pioneer work in staging of gynaecological tumours was done in the 1930’s with the publication of an atlas illustrating the division of cancer of uterine cervix into four stages by the League of Nations Health Organization. Since 1958 FIGO (Federation Internationale de Gynecologie et d' obstetrique) has been engaged in gynaecological tumour staging. Between 1960 & 1972 a clinical staging system was developed in collaboration with the UICC and the AJC (American Joint Committee for cancer staging and End Results Reporting).

The TNM (Tumour -Node -Metastasis) system introduced beetween 1943 and 1952 by Pierre Denoix at the Institute Gustav Roussy, Villejuif, France has gradually been forged to provide an international basis for categorizing cancers and to allow for comparable end results in reporting. The UICC and AJCC were constituted to develop a meaningful staging system using TNM categories in the early 1950's. After considerable dialogue, both groups published systems using the same TNM language but with stages defined differently. In 1982, at the 13th International Cancer Congress, an AJCC-UICC Joint meeting agreed to formulate a single TNM uniform staging system internationally accepted and approved by all national TNM Committees and by FIGO & SIOP (Societe Internationale d’Oncologie Pediatrique). The unified inter-nationally stage grouping is comparable with and translatable into former staging classifications e.g. the Dukes system and its various modifications, the Australian Clinico-pathological Staging System, or the Japanese Stage grouping for Colorectal Carcinoma or Robson's Staging system for renal-cell carcinoma.

The objectives of a classification system for cancer as defined by UICC are-

1) Aiding the clinician in planning treatment.

2) Giving some indications of prognosis.

3) Assisting in the evaluation of end results.

4) Facilitating the exchange of information among treatment centres.

5) Assisting in the continuing investigation of human cancer.

The quality of staging is vital to achieve the above objectives. Variations in staging procedures can affect the results in the same population. This refers to the clinical as well as to pathological classification. The same is true for different methods of pathological staging. Here, the choice of tissue blocks and the number of examined lymph nodes can be crucial. There are international efforts to recommend defined methods for staging, for example the proposals of the International Documentation System (IDS) for colorectal cancer.

The important staging systems currently in practice are-

TNM Staging

There are three basic variables

T: The extent of primary tumour.

N: The status of regional lymph nodes.

M: The presence or absence of distant metastases

To these three components are assigned a series of numbers (T 0, T 1. T 2, T 3 and T 4; No, N1, N2, and N3; Mo, M1) indicating ascending degrees of anatomical involvement of a particular malignant tumour. The TNM system is applicable to most solid tumour sites and entities. Exceptions are lymphomas and leukaemias, for which the TNM formula is not appropriate. TNM is a dual system that provides, first, a classification based on observations before starting treatment and then a classification using additional information that becomes available from surgery and histo-pathological examination. The TNM system allows a condensation of the many individual combinations of T, N, and M categories into a smaller number (usually four) of TNM stage groups which facilitates tabulation and statistical analysis. At present TNM classification exists for 46 tumour sites and entities.

Each patient is first classified clinically cTNM based on evidence acquired before treatment from physical examination, imaging, endoscopy, biopsy, surgical exploration, and other relevant examinations. The clinical TNM classification is the basis for selecting the primary treatment and for comparing results of different treatments. After surgical treatment and adequate histopathological examination the pTNM classification is made. It is, of course, more reliable than the cTNM classification and provides more accurate data to estimate prognosis and to evaluate results of surgical treatment. Moreover, pTNM is, together with the R classification, relevant for the selection of post- surgical radio- and/or chemotherapy.

Stage Grouping

The stage grouping should be such as to ensure, as far as possible, that each group is more or less homogenous in respect of prognosis and that the survival rates of these stage groups for each cancer site are distinctive. Generally there are four stages I-IV.

FIGO Staging System

FIGO has defined the most widely accepted staging system for carcinoma of cervix which is based on careful clinical examination and the results of specific radiological studies and procedures. These should be performed and the stage should be assigned before any definitive therapy is administered. The clinical stage should never be changed on the basis of subsequent findings. In its rules for clinical staging, FIGO states that palpation, inspection, colposcopy, endocervical curettage, hysteroscopy, cystoscopy, proctoscopy, intravenous urography and radiographic examination of the lungs and skeleton may be used for clinical staging. Suspected bladder or rectal involvement should be confirmed by biopsy. Examination under anaesthesia is desirable but not required.

Ann Arbor and Cotswolds staging classification of lymphomas

The Ann Arbor classification system with the Cotswolds modifications is used for the staging of Hodgkin's lymphomas and non-Hodgkin's lymphomas. This system is based on the fact that lymphoma usually spreads by contiguity to predictable lymph node sites. Four stages are recognised based on the extent of lymphatic involvement or the spread to distant extra-lymphatic organs. Lack of systemic symptoms is specified as A, whereas B indicates presence of unexplained weight loss greater that 10 %, fevers or night sweats. 

The International Lymphoma Study Group have recently provided a new revised classification for lymphomas known as REAL classification (Revised European-American classification of Lymphoid neoplasms). According to this, the lymphoma categorization is based on currently available morphologic, immunologic and genetic techniques. The present proposal divides lymphomas according to their immunophenotypes into B- and T -Cell neoplasms and then further according to the level of differentiation into precursor and peripheral types.

As earlier mentioned the staging should be arrived at, after careful clinical and investigational and pathological considerations, because the definitive line of management is decided on staging of the tumour. Very often, it is observed that the patients undergo treatment specially the surgical management without establishing the stage of the disease.  Therefore, when the primary care surgeon/physician refers a patient of malignant disease, they should provide the details of the preoperative findings so that the further planning of the management can be made accordingly.