Definition/Introduction

The TNM Classification is a system for classifying a malignancy. It is primarily used in solid tumors and can assist in prognostic cancer staging. A standard classification system improves communication between providers and allows for better information sharing and research across populations. The system is based on assessing the tumor, regional lymph nodes, and distant metastasis, as detailed below.

T - Tumor. Used to describe the size of the primary tumor and its' invasion into adjacent tissues. T0 indicates no evidence of tumor is present, while T1-T4 are used to identify the size and extension of the tumor, with progressive enlargement and invasiveness from T1 to T4. 

T-values are assessed differently based on the involved anatomic structures. For example, T1 indicates invasion into the submucosa in colorectal cancer, whereas T4 indicates tumor extension through all the layers of the colon and invasion of the visceral peritoneum or adjacent structures. T2 indicates an invasion of the muscularis propria, and T3 is an invasion into the subserosa. Tis identifies carcinoma in situ. Tx is used when the tumor is unable to be assessed.

N - Nodes. Used to describe regional lymph node involvement of the tumor. Lymph nodes function as biological filters, as fluid from body tissues is absorbed into lymphatic capillaries and flows to the lymph nodes.[1] N0 indicates no regional nodal spread, while N1-N3 indicates some degree of nodal spread, with a progressively distal spread from N1 to N3. 

N-values are assessed differently for specific tumors and their regional lymph node drainage. In colorectal cancer, N1 indicates the involvement of 1-3 regional nodes. N2 can be 4-6 regional nodes, while N3 indicates 7+ regional nodes involved. Nx is used when lymph nodes are unable to be assessed.

M - Metastasis. Used to identify the presence of distant metastases of the primary tumor. Metastasis is when the tumor spreads beyond regional lymph nodes. A tumor is classified as M0 if no distant metastasis is present and M1 if there is evidence of distant metastasis.

This classification can be further subdivided based on the tumor to provide more detailed information. In colorectal cancer classification, M1a indicates spread to 1 area, M1b is spread to 2+ areas, and M1c means spread to the peritoneal surface. Peritoneal carcinomatosis, in particular, is a poor prognostic factor for colorectal carcinoma.[2][3] The overall survival rate for peritoneal metastasis varies based on the primary tumor but can be as low as three months in the case of an unknown primary tumor.[4]

Issues of Concern

Cancer Grade Versus Stage

Cancer grading describes the microscopic appearance of the tumor's cells and tissue. Low-grade tumors have relatively normal-appearing cells and tissue structures. These tumors are considered well-differentiated. Higher-grade tumors have more abnormal-appearing cells and tissue that is structured abnormally. Higher-grade tumors are typically more aggressive and have a worse prognosis. They are described as poorly differentiated. The highest-grade tumors are termed undifferentiated.

Cancer staging describes the gross appearance of the tumor. It can include tumor size, invasion, spread to local lymph nodes, or distant metastasis. Some staging systems also include the grade of the tumor.

Many studies have demonstrated the value of cancer grade and stage in determining colorectal cancer prognosis.[5] Colorectal staging has been suggested to have the strongest association with survival.[6] Studies have further demonstrated considerable variation between pathologists in colorectal cancer grading, suggesting the importance of tumor staging for prognosis.[7] 

Population-Based Versus Personalized Cancer Staging

While the TNM system is useful as a classification system for carcinoma on a population level, its utility has been questioned on the individual patient level. Therefore, more personalized approaches have been suggested, including adding a molecular classification to the traditional approach to augment its overall utility. The Eighth AJCC Cancer Staging Manual has taken the early steps of acknowledging the importance of molecular oncology.[8]

Clinical Significance

The TNM system helps to establish the anatomic extent of the disease, and the combination of the three factors can serve to define the overall stage of the tumor. This method allows for simplification, with cancers staged from I-IV, with stage IV being the most severe stage. Stage 0 is used to indicate carcinoma in situ, which is not considered cancerous but may become cancer in the future. Stage V is used exclusively in Wilms tumors and occurs when both kidneys have involvement at initial diagnosis.[9] A simplified version of cancer staging and its relation to TNM classification is listed below. 

• Stage 0 - Indicates carcinoma in situ. Tis, N0, M0.
• Stage I - Localized cancer. T1-T2, N0, M0.
• Stage II - Locally advanced cancer, early stages. T1-T2, N1, M0.
• Stage III - Locally advanced cancer, late stages. T1-T4, N2-N3, M0.
• Stage IV - Metastatic cancer. T1-T4, N1-N3, M1.

Progressive cancer staging is associated with disease severity and decreased survival rates. Anal squamous cell carcinomas demonstrated an observed 5-year survival rate of 77% for stage I and only 15% for stage IV.[10] Colorectal carcinoma demonstrated a 5-year survival rate of 74% for stage I but only 5% for stage IV.[2]

Nursing, Allied Health, and Interprofessional Team Interventions

Cancer management is complicated and requires an interdisciplinary approach. Proper communication between medicine, oncology, surgery, pathology, and other services is paramount. Further, pharmacists, nursing staff, nutrition, social work, and case management should be closely involved in the care of these patients. Treatment can be curative or palliative, and approaches will vary based on the stage of cancer. Approaches can include elements of surgical removal, chemotherapy, and radiation. All healthcare team members should coordinate and agree on the proper treatment course for the individual patient. [Level 5]