Introduction

Cancer represents a complex group of diseases characterized by uncontrolled growth and the ability to metastasize. Cancer may affect any part of the body, and within the female reproductive systems, there exist a variety of cancers each associated with different presenting symptoms, clinical course, etiology, and natural history of disease. The essential features of each cancer include the presenting site of disease (topography), the histopathologic (morphology), molecular and genetic tumor profile, and the anatomic disease extent (stage). Without knowing these features, it is impossible to discuss investigation, treatment, and prognosis in cancer .

Classification: Taxonomy

Taxonomy is the science or practice of classification. It creates a framework for discussion, analysis, and information recording. In science, to facilitate the communication of findings, scientists must first give names to the subjects of their study and then arrange them in some order. This process of naming and arranging falls under the general rubric termed classification. Classification can be defined as a descriptive arrangement to enhance and enable communication and consistent identification to facilitate activities underpinning information storage and retrieval; the latter include such activities as compiling or retrieving categorical information in computer databases or internet searching to enhance clinical care, research and oncology administration, and cancer control. Such classifications are termed systematics and date back to the beginning of the biological studies by Aristotle about 300 B.C. that represented the first evidence of systematic classification in the animal world. Other recognized fathers of taxonomy or classification include Carolus Linnaeus who published the classification of living things in the 18th century. Furthermore, John Fothergill established the staging classification for diphtheria in which disease progression from stage I through to stage III corresponded to the severity of the disease, and it was the first recognized classification of disease severity .

Clinicians have classified all types of diseases for >80 years. The original classification of presenting diseases continues as the International Classification of Diseases (ICD) . The World Health Organization (WHO) states, “… The International Classification of Diseases (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This is used as a basis to analyze the general health of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems, proving a picture of the general health of countries and populations.” The ICD is currently under revision, and the new release of ICD 11 is planned for 2017 .

The ICD is further supplemented by the histopathologic classification, the International Classification of Diseases for Oncology (ICDO). The ICDO was developed mainly for use by tumor registries to code both the site (as per ICD10) and morphology of tumors. WHO states, “… The morphology axis provides five-digit codes ranging from M-8000/0 to M-9989/3 . The first four digits indicate the specific histological term. The fifth digit after the slash (/) is the behaviour code, which indicates whether a tumor is malignant, benign, in situ, or uncertain (whether benign or malignant). A separate one-digit code is also provided for histologic grading (differentiation)….”

The WHO Family of International Classifications (WHO-FIC) includes classifications endorsed by WHO to describe various aspects of the health and the health system. The aim of the FIC is to develop reliable statistical systems to improve health status and health care. The FIC classifies death, disease, functioning, disability, and health and health interventions ( Fig. 1 ).

Schematic representation of WHO Family of International Classifications ( http://www.who.int/classifications/en/FamilyDocument2007.pdf?ua=1 ).

Classification: Taxonomy

Taxonomy is the science or practice of classification. It creates a framework for discussion, analysis, and information recording. In science, to facilitate the communication of findings, scientists must first give names to the subjects of their study and then arrange them in some order. This process of naming and arranging falls under the general rubric termed classification. Classification can be defined as a descriptive arrangement to enhance and enable communication and consistent identification to facilitate activities underpinning information storage and retrieval; the latter include such activities as compiling or retrieving categorical information in computer databases or internet searching to enhance clinical care, research and oncology administration, and cancer control. Such classifications are termed systematics and date back to the beginning of the biological studies by Aristotle about 300 B.C. that represented the first evidence of systematic classification in the animal world. Other recognized fathers of taxonomy or classification include Carolus Linnaeus who published the classification of living things in the 18th century. Furthermore, John Fothergill established the staging classification for diphtheria in which disease progression from stage I through to stage III corresponded to the severity of the disease, and it was the first recognized classification of disease severity .

Clinicians have classified all types of diseases for >80 years. The original classification of presenting diseases continues as the International Classification of Diseases (ICD) . The World Health Organization (WHO) states, “… The International Classification of Diseases (ICD) is the standard diagnostic tool for epidemiology, health management and clinical purposes. This is used as a basis to analyze the general health of population groups. It is used to monitor the incidence and prevalence of diseases and other health problems, proving a picture of the general health of countries and populations.” The ICD is currently under revision, and the new release of ICD 11 is planned for 2017 .

The ICD is further supplemented by the histopathologic classification, the International Classification of Diseases for Oncology (ICDO). The ICDO was developed mainly for use by tumor registries to code both the site (as per ICD10) and morphology of tumors. WHO states, “… The morphology axis provides five-digit codes ranging from M-8000/0 to M-9989/3 . The first four digits indicate the specific histological term. The fifth digit after the slash (/) is the behaviour code, which indicates whether a tumor is malignant, benign, in situ, or uncertain (whether benign or malignant). A separate one-digit code is also provided for histologic grading (differentiation)….”

The WHO Family of International Classifications (WHO-FIC) includes classifications endorsed by WHO to describe various aspects of the health and the health system. The aim of the FIC is to develop reliable statistical systems to improve health status and health care. The FIC classifies death, disease, functioning, disability, and health and health interventions ( Fig. 1 ).

Schematic representation of WHO Family of International Classifications ( http://www.who.int/classifications/en/FamilyDocument2007.pdf?ua=1 ).

History of cancer staging

It has been recognized for many years that, in addition to topography and histopathology, the anatomic extent of disease is an important determinant of cancer prognosis, and that patients who present with extensive disease fare worse than those whose disease is much more localized. The classification of anatomic extent of disease is considered the “stage of disease.” .

One of the first formal attempts to classify stages in cancer was by the Radiological Sub-Commission of the Cancer Commission of the League of Nations Health Committee who wished to report cervical cancer treatment results. The group realized that it would only be possible to report results if disease extent was recorded in a uniform way, and those cases were grouped into different stages according to the extent of growth. Cancer of the uterine cervix thereby represents one of the first cancers for which a staging classification was developed. The first report was accepted and published in April 1929, and the system was known as the League of Nations staging system for cervical cancer. Since then, there have been numerous attempts to classify disease and extent in cancer. As noted earlier, the site of cancer is classified by the WHO ICD, histologic type by the WHO International Classification of Tumours and by the International Agency for Cancer Research (IARC), and the stage of cancer is classified by the TNM Classification maintained by the Union for International Cancer Control (UICC) and by the American Joint Committee on Cancer (AJCC). In gynecologic cancers, the International Federation of Gynecology and Obstetrics (FIGO) has maintained their own staging classification for >70 years. The International Classification of Stages of Uterine Cancer was adopted by FIGO, incorporated in 1954, and its oncology committee assumed the responsibility for the promotion and periodic revision of the staging system for gynecological cancers. Over the years, the UICC TNM and the AJCC TNM system developed in parallel, and they are now compatible with the FIGO classification .

The objectives of cancer staging

The objectives of cancer staging have been specified by the UICC for >60 years, and they are to aid treatment planning, provide an indication of prognosis, assist in the evaluation of treatment results, facilitate the exchange of information between treatment centers, contribute to continuing investigations of human malignancies, and to support cancer control activities, through cancer registries .

Cancer staging is essential to both patient care and research. Cancer control activities include direct patient care-related activities such as the definition of clinical practice guidelines, and more centralized activities such as recording of the disease extent in cancer registries . Accurate documentation of stage allows for the evaluation of disease in a population. Recording of stage is essential for the evaluation of outcomes of clinical practice guidelines and cancer programs. In order to evaluate the long-term outcomes of populations, it is important for the classification to be stable. There is therefore a conflict between recognizing a relevant classification that is used clinically, thereby reflecting and supporting the most current forms of management interventions, while also maintaining a classification that remains unchanged for decades. This function requires longitudinal studies and consensus .

The process of “staging” – investigations

The term “cancer staging” is frequently used to describe a set of procedures involved in delineating anatomic disease extent. Historically, this assessment was based on clinical examination and plain radiographic examination. These tools were grossly inadequate to assess the extent of disease in sites with assessment difficulties including intra-abdominal, intrathoracic, or indeed intracranial disease. Frequently, the disease extent was determined at the time of surgical exploration for either therapeutic or diagnostic purposes (e.g., exploratory or staging laparotomy). However, the past four decades have witnessed an explosion of diagnostic imaging tools including computerized tomography (CT), magnetic resonance imaging (MRI), ultrasound, functional positron emission tomography (PET) imaging, and biomarker determination as surrogates of disease extent (e.g., beta subunit of human chorionic gonadotropin (β-hCG), alpha-fetoprotein (AFP), prostate-specific antigen (PSA), carcinoembryonic antigen (CEA), cancer antigen (CA)125, Ca19-9, etc.). Today, staging investigations include clinical examination, imaging, image-guided biopsies, and biomarker determination.

Clinical and pathologic stage

With the exception of hematologic malignancies, cancer stage is based on the TNM system . The TNM system comprises the T category for the primary tumor, the N category for the absence, presence, or extent of regional lymph node metastasis, and the M category indicating the absence or presence of distant metastasis. The TNM may be defined as clinical TNM and pathologic TNM or pTNM classification.

These two versions of the staging classification differ and serve different purposes. The first, the “clinical staging” classification, describes the extent of disease determined by clinical examination, imaging, as well as endoscopic and other interventions and biopsies, whereas the second, “pathological staging,” relies on clinical and pathologic information derived following the surgical removal of the primary tumor and/or lymph nodes. The major differences between clinical and pathological stage are in nonmetastatic disease where clearly much more detail is available if the primary tumor is removed and subjected to the microscopic examination. Consequently, “pathologic stage” is likely to be different from “clinical stage” and a potentially more accurate predictor of outcome than the clinical stage. However, in many clinical situations today, first the treatment is directed by “clinical stage,” whereas “pathologic stage” is used to direct adjuvant therapy. Moreover, primary treatment with radiotherapy and or chemotherapy that does not include surgery is always based on clinical stage.

The pathological TNM classification does not replace the original clinical TNM classification, but it provides additional information. Realistically, however, the determination of disease extent is never 100% accurate, and whether clinical or pathologic, our ability to determine true disease extent is imperfect. This is manifested by disease recurrence either locally or in distant sites after the complete control of originally localized tumor because of the presence of occult residual disease or micrometastasis at the time of initial presentation. Therefore, the “stage” is recognized as not realistically describing the true disease extent in every patient but generally represents the best and most reasonable approximation based on investigations.