Staging of Colorectal Cancer (CRC)


Staging of cancer is intended to find out the extent of cancer in the body. There are two types of staging, clinical and pathologic.  

Accurate staging of CRC is imperative for the determination of adjuvant therapy and prognosis. Cuthbert Dukes established the first staging system in the 1930’s. This system used an A, B or C for classification however, despite its simplicity it was not viewed as precise enough to adequately describe the tumor depth or positive lymph node status. In 1998, the AJCC and the International Union for Cancer Control (UICC) combined efforts to develop a system that would gain international consistency (Sweede, 2001). This system, the tumor, node, metastasis (TNM) classification is widely accepted with the latest revision, the 7^th edition, taking effect for all cases diagnosed on or following January 1, 2010. Traditionally this system focused on the anatomical extent of the disease.  At a time where biology provides prognostic information critically impacting clinical oncology, a challenge and opportunity is set for the AJCC to incorporate this aspect into nomenclature to maintain usefulness of this system (Edge, 2010).

Through obtaining a comprehensive medical history, performing a physical examination, evaluation of radiographic findings and details of colonoscopic findings, the physician attempts to establish the clinical staging of the disease (cTNM). The pathologic staging (pTNM) occurs following surgery which not only removes the primary tumor but also explores the abdomen and lymph nodes for pathologic examination of all specimens. The y prefix (yTNM) is used for staging following neoadjuvant therapy and the r (rTNM) prefix is used to designate recurrence after a disease –free interval (AJCC, 2010; ACS, 2011).

Staging of CRC is based on the depth of tumor penetration through the bowel wall or adherence to adjacent organs or structures (T), degree of presence of regional lymph node involvement (N) and presence or absence of distant metastasis (M). Evidence supports that the number of lymph nodes dissected is not only therapeutic but also a prognostic indicator. The AJCC and the College of American Pathologists (CAP) recommend identification of 12 lymph nodes as a minimum to adequately stage    CRC (Comptom, 2004; Sobin, 2001).

Tumor, Node, Metastasis (TNM) Definitions

Based on information from NCCN (2011) and AJCC (2010). Note: Highlighted areas denote changes from the AJCC 6^th to the AJCC 7^th edition.

The factors contained within the TNM definition chart serve as a guide to stage delineation. To better understand the staging system, familiarity with an image of the colon and its respective layers can assist in visualization of what is happening physiologically.

Colon Cancer TNM Staging: Tumor Size, Invasion and Spread

The staging system is categorized from Stage 0 through stage IVB. The element of disease- risk or prognosis correlates with the stage or extent of disease.  The depth of tumor penetration in stage I disease can be into the submucosa (T1) or the muscularis propria (T2). In stage IIA - IIC CRC, the tumor penetration can span through the muscularis propria to pericolorectal tissues, may continue to the surface of the visceral peritoneum or directly invade or adhere to other organs or structures however, there is no lymph node involvement. Nodal involvement begins in stage IIIA – IIIC. The depth of tumor penetration in addition to the number of regional lymph nodes and tumor deposit is dependent on association is concordant with higher staging. Finally, stage IVA – IVB incorporates one distant organ involvement (M1a) or greater than 1 organ/peritoneal involvement (M1b), with any size tumor and any number of positive regional lymph nodes.

Colon Cancer Staging (TNM) and 5-Year Survival by Stage

* The AJCC doesn’t give a 5-year survival rate for stage IIC. The ACS 5-year survival rate for stage IIC is 37%.     Based on information from AJCC (2010). Note: Five year percentages based on data prior to institution of 7^th edition, AJCC staging guide.

Advances in surgical pathology findings have enabled expansion for disease prognosis and prediction to treatment response and outcomes. Essential to any pathology report are the following elements: grade of the cancer, depth of tumor penetration, number of regional lymph nodes evaluated and number of those positive, assessment of distant metastasis and the status of surgical margins (NCCN, 2011). The AJCC staging system specifies that surgical resection is scored regarding completeness. Scores are as follows: R0 designates complete resection with all margins negative for tumor, R1 is an incomplete resection with microscopic involvement of a margin and R2 resection has gross residual tumor (AJCC, 2010).

Based on data that KRAS mutations predict for lack of response to therapy with anti-EGFR monoclonal antibodies, testing for KRAS mutations at the time of diagnosis of stage IV disease has been strongly recommended by the NCCN panel (NCCN, 2011; Baselga, 2008; Karapetis, 2008; Imclone, 2011; Amgen, 2011). To date, there is inconclusive evidence for BRAF V600E mutations and responses with anti-EGFR monoclonal antibodies however there is retrospective data that the V600E BRAF mutation confers a poor prognosis regardless of treatment (VanCutsem, 2010). DNA mismatch repair (MMR) gene ( e.g., MLH1, MSH2, MSH6) mutations or modifications can result in MMR deficiency. Germline mutations can be associated with hereditary nonpolyposis colon cancer (HNPCC) and 10-15% of sporadic colon cancers. Microsatellite instability is a marker for MMR deficiency (Kim, 2007).  The NCCN panel recommends that MMR protein testing be conducted in patients < 50 years of age, because of the increased possibility of HNPCC in this population. Additionally, this testing is recommended for patients with stage II disease where fluoropyrimidine therapy is being considered, as there is evidence that MMR deficiency is predictive for response to therapy (Sargent, 2008).

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