TNM Cancer Classifications and What They Mean

Author: Alina Yang

Editors: Hwi-On Lee, Justin Tai

Artist: Emily Tai

Some say cancer is the will of god and that it bestows upon you a consumption rogue and ravenous – somewhat like a divine punishment. Some say that cancer is the influence of evil spirits, cursing you and bringing upon an insidious malediction – a supernatural force autonomous and incapable of being quelled.

These were the beliefs of ancient Egyptians. The Edwin Smith Papyrus, dating back to 1600 BCE, is one of the earliest known medical texts to mankind. It described tumors and their respective empirical treatments but also included prayers and magical spells alongside medical interventions, signifying the belief of ancient Egyptian physicians that illnesses, such as cancer, could result from displeasing the gods or from malevolent, spiritual forces attacking the body. The treatments described within the papyrus often included rituals, amulets, offerings to deities, and practical remedies like surgery or herbal medicine. This superstition persisted for centuries and influenced other civilizations’ medical theories until scientific advancements provided a biological understanding of cancer actually in the human body.

Cancer remains a mortal enigma; while we classify and treat cancer with precise medical technology in the modern era, the disease has been recognized – though misunderstood – for millennia. Although a contemporary subject, cancer has historical footprints that stretch beyond the Renaissance, when dissection and scientific exploration advanced the human understanding of cancer. However, it wasn’t until the late 20th and early 21st centuries that medical classification systems, like the Tumor, Node, Metastasis (TNM) staging system, allowed for more precise diagnoses and treatment strategies.

Developed by the Union for International Cancer Control (UICC) and the American Joint Committee on Cancer (AJCC), the TNM cancer classification system is a globally recognized method for staging cancer. This system helps oncologists assess the severity of cancer, predict prognosis, and determine the best course of treatment. TNM stands for:

T - Tumor, which describes the size and extent of the primary tumor.
N - Node, which indicates if cancer has spread to nearby lymph nodes.
M - Metastasis, which identifies whether cancer has spread to other parts of the body.

Despite the similarities of the broader categorization of cancer, it is important to understand that the subclassifications of cancer that help determine the severity will have different definitions in their unique staging criteria based on the anatomy and behavior of that specific cancer. When determining cancer staging, oncologists must always refer to the staging guidelines for the particular type of cancer in question issued by the American Cancer Society (ACS), which has evolved with new scientific data as new screening technologies have become available. As such, the TNM naming system remains a guide to treatment decisions.

The T category describes the size and spread of the primary tumor. It ranges from T0, indicating no detectable tumor, to T4, representing a large or extensively invasive tumor. Tx implies that the tumor cannot be evaluated, meaning the tumor does not show on scans, but cancer cells may be present in body fluids or tissue samples. T0 means that there is no evidence of a primary tumor – it cannot be found. Occasionally, early-stage cancer occurs where abnormal cells remain confined to their original layer of tissue and have not invaded deeper structures, which is referred to as Carcinoma in situ. In this stage, any abnormal cells are contained within a single localized area and have not yet formed a detectable mass. T1 implies that cancer is present in the organ and can be split into various T1 phases: T1mi, T1a, T1b, and T1c. Adenocarcinoma, a non-small cell cancer, is described as T1mi, a condition that starts in the glands and lines the original organ. Stages T1a to T1c describe the precise diameter of the cancer, but these descriptors vary from cancer to cancer.

For tumors that have developed beyond this stage, numerical values are assigned to indicate the size and extent of spread. T2 tumors are larger and potentially have begun to invade nearby structures, such as surrounding connective tissue or the inner lining of organs. T3 tumors typically show more significant local spread, possibly involving adjacent tissues, muscles, or major blood vessels. T4 tumors are extensive, often infiltrating neighboring organs or structures, making surgical removal more difficult or sometimes impossible. The T stage plays a crucial role in determining treatment approaches relating to the severity of the tumor; smaller tumors confined to one area are more likely to be treated with surgery or localized therapies, while larger, more invasive tumors may require a combination of treatments such as chemotherapy and radiation.

Following the T category, the N category evaluates whether cancer has spread to nearby lymph nodes, part of the body’s immune system. Lymph node involvement is an essential factor in staging cancer because it often indicates a higher likelihood of further metastasis. Nx, like Tx, implies that the cancer cannot be assessed. N0, similar to T0, suggests no evidence of cancer cells in the lymph nodes.

N1 signifies that cancer cells are present in nearby lymph nodes, usually those closest to the primary tumor. N2 describes more extensive lymph node involvement, where the cells spread to further nodes from the original tumor site but still within the same general region, and N3 means that cancer has reached distant lymph nodes, such as those on the opposite side of the body or in more distant locations. Cancers that have spread to lymph nodes often require systemic treatments including chemotherapy, targeted therapies, or immunotherapy, to address potential microscopic spread beyond the initial tumor site, significantly increasing the complexity of treatment.

The M category determines whether cancer has spread beyond the original site to distant organs. This factor is often the most critical in determining prognosis and treatment options. M0 means there is no evidence of distant metastasis, and the cancer remains confined to the primary site and nearby lymph nodes. M1 indicates that cancer has spread to distant organs or tissues, increasing treatment difficulty. M1 is further divided into subcategories to reflect the extent of metastatic spread:

M1a suggests limited spread, such as cancer in both lungs or the presence of malignant fluid collections around the lungs or heart.
M1b means there is a single metastatic tumor in a distant organ, such as the liver, brain, or bones.
M1c signifies multiple metastatic sites in one or more distant organs, representing the most advanced stage of cancer.

Once cancer has metastasized, treatment is typically focused on managing symptoms and slowing progression rather than achieving a complete cure. Systemic therapies, such as chemotherapy, immunotherapy, and targeted drugs, are often used to prolong and maintain quality of life.

The stage of cancer, determined by the TNM classification, is crucial in selecting the most effective treatment plan. Other factors, such as cancer type, genetic mutations, tumor location, and overall patient health, also influence treatment decisions.

Localized cancer (low T stage, N0, M0) may be treated with surgery, radiation therapy, or a combination of both. Cancers with lymph node involvement (higher N stages) often require additional treatments, such as chemotherapy or immunotherapy, to eliminate microscopic cancer cells that may have spread. Metastatic cancer (M1 stage) is usually treated with systemic therapies, including chemotherapy, targeted therapies, or immunotherapy, rather than localized treatments like surgery.

In some cases, recent treatment options such as radiofrequency ablation (RFA), photodynamic therapy (PDT), or palliative care, may be used to manage symptoms and improve quality of life. Advances in cancer research continue to refine staging methods and treatment strategies, offering hope for more personalized and effective approaches to cancer care.

The TNM system remains a cornerstone of oncology, guiding clinical decisions and cancer research. Providing a standardized framework for assessing cancer severity helps doctors worldwide determine the best possible treatments and improve patient outcomes.

Citations:

American Cancer Society. (2024). Cancer Staging. Www.cancer.org.

https://www.cancer.org/cancer/diagnosis-staging/staging.html

American College of Surgeons. (n.d.). Cancer Staging Systems. ACS.

https://www.facs.org/quality-programs/cancer-programs/american-joint-committee-on-

cancer/cancer-staging-systems/

Cancer Research UK. (2023, January 3). TNM staging | Lung cancer | Cancer Research UK.

Cancerresearchuk.org. https://www.cancerresearchuk.org/about-cancer/lung-

cancer/stages-types-grades/tnm-staging

Cleveland Clinic. (2021). Adenocarcinoma Cancers: Symptoms, Causes, Diagnosis & Treatment.

Cleveland Clinic. https://my.clevelandclinic.org/health/diseases/21652-adenocarcinoma-

cancers