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TNM Stage in Colorectal Cancer
It allows for the incorporation of all technological approaches to staging, and has a comprehensive set of definitions and rules of application that ensure uniform use.8 It provides a standardized format for information on disease burden that is gathered during the assessment of the cancer patient, no matter what methods or approaches are used. It is the common language used to describe and codify the extent of the patient's disease and conveys essential prognostic information.
In the TNM system, the designation "T" refers to the local extent of the untreated primary tumor at the time of diagnosis and initial work-up. The designation "N" refers to the metastatic status of the regional (draining) lymph nodes, and "M" refers to distant metastatic disease at this time. The symbol "c" used as a prescript refers to the clinical determination of T, N, and/or M (e.g., cT3), as contrasted with the pathological determination of T or N (designated by the prescript "p"). Clinical classification (cTNM) is based on evidence acquired through a variety of techniques that include but are not limited to physical examination, radiologic imaging, endoscopy, biopsy, and surgical exploration. Pathologic classification is based on gross and microscopic examination of the resection specimen of a previously untreated primary tumor. Assignment of pT requires a resection of the primary tumor or biopsy adequate to assess the highest pT category; pN entails removal or biopsy of regional nodes adequate to evaluate lymph node metastasis; and pM1 indicates microscopic examination of distant lesions. The designation pM0 does not exist since it implies pathological exclusion of distant metastasis anywhere in the body, an act that could only be accomplished at autopsy.1,3,8,9
General Rules for Staging
Masses or ulcers discovered by rectal examination, imaging or endoscopic studies that are suspicious for colorectal carcinoma typically require biopsy confirmation as carcinomas before initiating treatment. In situations where pathological diagnosis is not possible, microscopically unconfirmed cases may be staged clinically but should be analyzed and reported separately. This rule also applies to cases in which neither biopsy confirmation nor surgical resection is possible. Although clinical diagnosis of established colorectal carcinomas is usually accurate, a number of benign and malignant conditions that may mimic colonic carcinoma grossly require exclusion on biopsy. For example, other tumors that may resemble colorectal carcinoma include colorectal lymphomas, carcinoid tumors, gastrointestinal stromal tumors (mural sarcomas), metastatic tumors that exhibit tropism for the gastrointestinal tract (e.g., malignant melanoma), malignancies of adjacent organs that directly invade the colorectum (e.g., cancers of the ovary, endometrium, bladder, or prostate) or appendiceal tumors that extend into the cecum. Since TNM staging for the colorectum is applicable only to primary carcinomas of the colon and rectum, these tumors would all be excluded from classification by the colorectal TNM system and most would be staged by other TNM systems. Benign lesions that may mimic colorectal cancer include adenomas, hamartomas, solitary rectal ulcers, stercoral ulcers, endometriomas, and Crohn's disease or diverticular disease producing mural strictures.8
Clinical staging ends after the diagnostic work-up if a decision is made not to treat the patient. It is considered the definitive stage if pathologic classification is not possible. The clinical staging parameters evaluated prior to treatment are reported separately and remain unchanged in the patient's medical record as documentation of the basis for treatment planning. They may be revised only if more accurate clinical staging information becomes available (e.g., higher resolution imaging studies) before initiation of treatment or before making the decision not to treat the patient. In such cases, the revised classification is considered the definitive clinical stage. When pathologic information becomes available following surgical resection, it is used to derive the final stage assignment. By convention, pathologically-derived parameters are considered more accurate than clinically derived parameters and, therefore, stand as the ultimate determination of T, N, or M1. The final stage grouping assigned to a patient is often a composite of pathologically and clinically derived parameters (e.g., pT3, pN1, cM0).1
The general rule for uncertainty in TNM staging is that conservative interpretation is always used. This rule insures consistent interpretation in cases in which the cut-point between two possible staging parameters is unclear. For example, if uncertainty exists between assignment of T3 or T4, either clinically or pathologically, T3 is always assigned according to this rule.1
If more than one carcinoma is present in the colorectum simultaneously, each is assigned a stage and an anatomic subsite, but the one with the highest stage defines the patient management plan.
Updated TNM Staging for Colorectal Cancer
In the 7th Edition of the AJCC Cancer Staging Manual, changes have been made for the colon and rectum sites based on data accrued since the development of the 6th Edition. The changes are as follows:1
The definition of Stage II (node-negative, M0).
In the 6th Edition, Stage II was subdivided into IIA and IIB based on whether the primary tumor was T3 or T4, respectively. However, expanded data sets have shown differential prognosis within both the T3 and T4 categories. The definition of T3 has been expanded to include the adverse impact of peritumoral deposits or "satellite nodules" (SN) on outcome, whether or not the tumor has penetrated the muscularis propria by direct extension. Tumor that invades through the muscularis propria is now classified as T3a, and tumor that does not invade through the muscularis propria but is associated with peritumoral satellite nodules or tumor deposits in the extramural soft tissue is classified as T3b. These satellite nodules were formerly classified as lymph nodes replaced by metastatic tumor and each counted separately in the N category.
T4 lesions are now subcategorized as T4a (penetrates visceral peritoneum) and T4b (directly invades or is histologically adherent to other organs or structures). According to increasing relative risk, Stage Group II is now subdivided into IIA (T3a/b,N0), IIB (T4a,N0) and IIC (T4b,N0).
Accurate determination of stage II disease (i.e., transmural, localized tumor without regional nodal metastasis) is critical because it largely determines whether adjuvant therapy should be administered. Additional stage-independent adverse prognostic factors such as lymphatic, venous, or neural invasion or high tumor grade, for example, may be important to consider in identifying stage II patients at additional risk who might benefit from adjuvant therapy.
The definition of Stage III (node-positive, M0) has been revised.
The number of nodes involved with metastasis has been shown to influence prognosis within both N1 (1-3 positive nodes) and N2 (4 or more positive nodes) groups. Accordingly, N1 is now subdivided as N1a (metastasis in 1 regional node) and N1b (metastasis in 2-3 nodes), and N2 is subdivided as N2a (metastasis in 4-6 nodes) and N2b (metastasis in 7 or more nodes). In addition, a category of N1 lesions, T4b,N1, that was formerly classified as IIIB was found to have outcomes comparable to IIIC and, accordingly, is now reclassified as IIIC. Similarly, several categories of N2 lesions formerly classified as IIIC have been outcomes more akin to other stage groups and have been reclassified as follows: T1N2a is reclassified as IIIA; and T1N2b, T2N2a-b, T3N2a, and T4aN2a are all reclassified as IIIB. According to increasing relative risk, Stage III is now subdivided into IIIA (T1-2,N1), IIIB (T3-4,N1) or IIIC (any T,N2).
New site-specific factors have been defined for routine assessment and documentation.
Five new site-specific factors are recommended for routine assessment as appropriate in given cases, in addition to serum CEA levels as previously recommended. The new site-specific factors include: 1) satellite nodules (SN: the number of peritumoral nodules or deposits of tumor that lack evidence of residual lymph node); 2) tumor regression grade for neoadjuvantly treated tumors; 3) the status of the circumferential resection margin (CRM status: the surgical clearance is to be measured in mm from the leading edge of tumor to the nearest dissected margin of the surgical resection); 4)microsatellite instability (MSI), an important prognostic and predictive factor for colon cancer; and 5) perineural invasion (PN: histological evidence of invasion of regional nerves, which may be similar to lymph vascular invasion as an adverse prognostic factor).
The anatomic boundary between the rectum and the anal canal has been better defined pathologically.
With advances in sphincter-preservation surgery, however, the anorectal boundary is more appropriately defined as the anorectal ring, which corresponds to the proximal border of the puborectalis muscle palpable on digital rectal examination. Accordingly, the anorectal boundary will be clinically defined but obscure on pathological examination.