Introduction and Overview
The extent or stage of cancer at the time of diagnosis is a key factor that defines prognosis and is a critical element in determining appropriate treatment based on the experience and outcomes of groups of previous patients with similar stage. In addition, cancer stage often is a key component of inclusion, exclusion, and stratification criteria for clinical trials. Indeed, accurate staging is necessary to evaluate the results of treatments and clinical trials, to facilitate the exchange and comparison of information across treatment centers and within and between cancer-specific registries, and to serve as a basis for clinical and translational cancer research. At the national and international levels, a cohesive approach to the classification of cancer provides a method of clearly conveying clinical experience to others without ambiguity.
Cancer treatment requires assessment of the extent and behavior of the tumor and patient-related factors. Several cancer staging systems are used worldwide. Differences among these systems stem from the needs and objectives of users in clinical medicine and in population surveillance. The most clinically useful staging system is the tumor, node, and metastasis (TNM) staging system developed by the American Joint Committee on Cancer (AJCC) in collaboration with the Union for International Cancer Control (UICC), herein referred to as the AJCC TNM staging system. The AJCC TNM system classifies cancers by the size and extent of the primary tumor (T), involvement of regional lymph nodes (N), and the presence or absence of distant metastases (M), supplemented in recent years by evidence-based prognostic and predictive factors. There is a TNM staging algorithm for cancers of virtually every anatomic site and histology, with the primary exception of pediatric cancers.
The AJCC and UICC periodically modify the AJCC TNM staging system in response to newly acquired clinical and pathological data and an improved understand ing of cancer biology and other factors affecting prognosis. Periodic and , to the extent possible, evidence-based revision is a key feature that makes this staging system the most clinically useful among staging systems and accounts for its widespread use worldwide. However, because changes in staging systems may make it difficult to compare outcomes of patients over time, evidence-based changes to this staging system are made with deliberate care.
In general, the revision cycle for AJCC TNM staging has historically been 5 to 7 years. This approach provides sufficient time for implementation of changes in clinical management and cancer registry operations and for relevant examination and discussion of data supporting changes in staging. Table 1.1 shows the publication year for each version of the AJCC TNM system up through this current AJCC Cancer Staging Manual, 8th Edition. The AJCC Cancer Staging Manual, 7th Edition was used for cancer patients diagnosed on or after January 1, 2010. The 8th Edition published in this manual is effective for cancer patients diagnosed on or after January 1, 2018. The AJCC recognizes that rapidly evolving evidence may necessitate more frequent updates of AJCC TNM staging in the future, and anticipates providing more frequent updates for disease sites as new and validated evidence becomes available. Moreover, the AJCC also recognizes that as clinical cancer care continues to evolve and incorporates factors that are not used to determine stage but that provide key information on specific outcomes and /or expected benefit from specific therapies, new, validated clinical tools will be needed to help clinicians efficiently and accurately use these important data to enhance clinical care (see Anatomic Staging and the Evolving Use of Nonanatomic Factors).
In January 2012, the AJCC and UICC initiated a comprehensive analysis of staging nomenclature: the AJCC-UICC Lexicon Project. This effort focused on harmonization of their collective staging taxonomies with each other and with international stand ards. This group concluded that terminology should be categorized into four main groups: (1) anatomic stage—disease extent and timing/classification; (2) tumor profile—characterization of tumor (e.g., biomarkers, viral load); (3) patient profile—age, gender, race, and health status; and (4) environment—availability of treatment and quality of imaging. This joint project thus far has encompassed two working groups—anatomic stage and tumor profile—to thoroughly review the existing nomenclature and stand ard definitions. The patient profile and environment categories will be addressed in future work.
The Content Harmonization Core (CHC) is one of seven AJCC “cores” developed to inform a more uniform 8th Edition effort. The CHC had its first meeting in August 2014. Building upon the work of the AJCC-UICC Lexicon Project, its charge was to review and update the general staging rules and nomenclature (published in Chapter 1 of the 7th Edition) and to develop a more precise language of cancer to enhance the accuracy of the staging system. A goal of this effort is to stand ardize technical terms and concepts as well as conflicting terms and usage. Once it identified key issues, the CHC worked with thought leaders and organizations to clarify and ensure precise, stand ardized, and clear definitions and rules for staging to the extent possible; for some terms and concepts, however, unequivocal clarity could not be achieved (and is noted in the chapter). The work product of the CHC is reflected in this chapter, and provides overall rules for staging that apply across all tumor sites. In most cases, the rules are unchanged from previous versions of TNM; to the extent possible, ambiguities have been resolved. Although the rules generally apply across all disease sites, there are some exceptions as to how these rules are applied to specific disease sites. Wherever possible, such exceptions are noted, both in this chapter and in the appropriate disease site chapters.
Staging requires the collaborative effort of many professionals, including the managing physician, pathologist, radiologist, cancer registrar, and others. The pathologist plays a central role. An accurate microscopic diagnosis is essential to the evaluation and treatment of cancer. Pathologists must also accurately report several anatomic, histologic, and morphologic characteristics of tumors, as well as key biologic features. Pathological reporting is best accomplished by using stand ardized nomenclature in a structured report, such as the synoptic reports or cancer protocols defined by the College of American Pathologists (CAP). In addition, for some cancers, measurements of other factors, including biochemical, molecular, genetic, immunologic, or functional characteristics of the tumor or normal tissues have become important or essential elements to improve tumor classification. Some of the growing repertoire of techniques that supplement stand ard histologic evaluation used to characterize tumors and their potential behavior and response to treatment include immunohistochemistry (IHC), cytogenetic analysis, and genetic characterization in the form of mutational analysis. Similarly, imaging specialists must provide concise and unambiguous reports on the extent of cancer as identified on a variety of imaging studies.
Although the pathologist and the radiologist provide important staging information, and may provide important T-, N-, and /or M-related information, stage is defined ultimately from the synthesis of an array of patient history and physical examination findings supplemented by imaging and pathology data. Only the managing physician can assign the patient's stage, because only (s)he routinely has access to all the pertinent information from physical examination, imaging studies, biopsies, diagnostic procedures, surgical findings, and pathology reports.
In the interest of promoting high-quality care, and to facilitate international collaboration in cancer research and comparison of data among different clinical studies, the AJCC uses information from other organizations and publications to facilitate staging, including:
Historically, cancer staging has been based solely on the anatomic extent of cancer, and the 8th Edition approach remains primarily anatomic. However, an increasing number of nonanatomic cancer- and host-related factors provide critical prognostic information and may predict the benefit of specific therapies. Among factors shown to affect patient outcome and /or response to therapy are the clinical and pathological anatomic extent of disease; the reported duration of signs or symptoms; the gender, age, and health status of the patient; the tumor type and grade; and specific biological properties of the cancer and host. Clinicians often use pure anatomic extent of disease in defining treatment, but in many cases, they supplement TNM-based staging with other factors to counsel patients and offer specific treatment recommendations. As more of these and other factors are embraced, applying them in practice will become increasingly complex. This will make it essential to initiate strategies to develop clinically validated prognostic tools and incorporate them into practice to enhance patient management and overall clinical decision making, ideally while maintaining a core anatomic-based structure of staging. Such an integrated approach may reduce the potential for the de facto anatomically constrained TNM system to be rendered obsolete by fostering incorporation of an unprecedented and rapidly evolving understand ing of the biology of human cancer. See also Chapter 4, Risk Assessment Models, for more information on AJCC-initiated efforts to embrace development of clinically validated tools.
As introduced in this chapter and detailed throughout this cancer staging manual, in many of the revised AJCC staging algorithms, prognostic factors have been incorporated into stage groupings for specific disease sites where indicated. Because this practice was initiated in a limited fashion in previous editions, most prognostic factors in use, if validated, have been done so only for patients with specific types of disease stratified largely by anatomic stage (e.g., Gleason score in early-stage prostate cancer and genomic profiles in women with node-negative breast cancer). It is important to recognize that even with these advances, anatomic extent of disease remains central to defining cancer prognosis. Inclusion of anatomic extent also maintains the ability to compare patients in a similar fashion across both contemporary and historical treatment regimens and eras, as well as patient populations for whom new prognostic factors cannot be obtained because of cost, available expertise, reporting systems, and /or other logistical issues.