Uterine Cancer: Stages and Grades

Assessing the severity and aggressiveness of uterine cancer is important in guiding its diagnosis, treatment and prognosis. Three key factors are used to assess the progression of uterine cancer — stage, cell type and grade. Stage describes the extent of tumor growth and cancer spread while cell type and grade indicate the aggressiveness of the cancer. New molecular systems of classification of endometrial cancer are evolving and may better predict cancer behaviour. Understanding these classifications will help you and your healthcare provider to determine the best course of treatment.

Cancer staging is a codified process which determines the extent of cancer in your body. It typically considers the size of the tumor and the extent of cancer spread. Staging is important as it ensures that each patient receives the most effective form of treatment for their condition. It also allows for balanced comparison of treatment outcomes.

Uterine cancer is staged surgically, whereby tissues removed during a hysterectomy are examined. This assesses how deeply the cancer has invaded the uterus and if it has spread to other organs. Lymph node assessment during surgery is typically recommended as a best practice. Surgical staging provides the most accurate and comprehensive assessment of the extent of uterine cancer.

Uterine cancer can also be staged clinically, typically for patients who are unable to undergo immediate surgery. Clinical staging provides an approximation of the spread of cancer based on results from physical examinations, imaging tests and biopsies. It is less accurate than surgical staging, but it can still provide a rough picture of a patient’s prognosis.

Uterine cancer is typically only staged at the point of diagnosis. However, if a new tumor develops, the patient is reevaluated, often by radiologic imaging, and the patient may be assessed as having recurrent uterine cancer. Nonetheless, this does not change the original stage of cancer assigned to the patient. Instead, it is used to guide decisions about further treatment.

Staging of uterine cancer follows 2 main classification systems — the American Joint Committee on Cancer (AJCC) TNM system and the FIGO (International Federation of Gynecology and Obstetrics) system. While both systems are closely aligned, the FIGO system is a specialized system only used in gynecologic oncology and is the most typically employed. On the other hand, the AJCC TNM system is a more generic system that can be applied to all cancer types.

AJCC TNM system

The AJCC TNM system assesses the stage of cancer based on 3 broad categories — tumor (T), nodes (N) and metastasis (M). For uterine cancer, the categories are defined as:

• Tumor (T): Assesses the size of the primary tumor and whether it has grown into the uterine wall or surrounding structures.
• Nodes (N): Assesses whether the cancer has spread to lymph nodes within the pelvis region.
• Metastasis (M): Assesses whether the cancer has spread to other parts of the body outside the pelvis region.

Each category is further assigned a number to describe the degree of cancer progression in that domain (e.g. T0). The higher the number, the more advanced the cancer is in that category. Letters may also be assigned to each category to reflect the extent or type of diagnostic information available in that particular domain (e.g. TX).

FIGO system

The FIGO system classifies uterine cancer into four stages (1–4) based on the extent of spread of cancer:

• Stage 1 (I): Cancer is confined to the uterus.
• Stage 2 (II): Cancer has spread to the cervical stroma but is still confined within the uterus.
• Stage 3 (III): Cancer has spread locally/regionally but is still within the pelvis or involves the lymph nodes.
• Stage 4 (IV): Cancer has spread outside of the pelvis region into the bladder or rectum.

Each stage can further be divided into substages, which are represented by letters (A, B and C). These substages provide further information on the extent and specific characteristics of the cancer within each main stage.

While the two staging systems differ in their structure, they are aligned in the assignment of cancer stage classification. Similar to most cancers, uterine cancer can be broadly classified into five stages (stage 0–4). Each stage is further stratified into subdivisions depending on the extent of cancer progression within that stage.

Cancer grading assesses how abnormal cancer cells look under a microscope. It provides insights into how aggressive the tumor might be. Uterine cancer can be classified into three grades, differentiated based on how much the cancer cells resemble normal, healthy uterine tissue:

• Grade 1 (G1): Tumor tissue contains up to 5% of solid tumor growth. They are typically less aggressive and less likely to spread to other areas of the body.
• Grade 2 (G2): Tumor tissue contains 6–50% of solid tumor growth. They tend to grow faster and have a higher risk of spreading.
• Grade 3 (G3): Tumor tissue contains more than 50% of solid tumor growth. They are more aggressive, grow quickly and are highly likely to spread to other areas of the body.

Low-grade uterine cancer tumors (G1 and G2) are less aggressive and generally resemble normal uterine tissue. On the other hand, high-grade uterine cancer tumors (G3) are more aggressive and no longer resemble normal uterine tissue. Patients with high-grade uterine cancer are at a higher risk of recurrence and usually require more intensive treatment.

The cell type of uterine cancer refers to the specific type of cell that the cancer originates from. This determines its behaviour and response to treatment. Higher risk cell types include serous and clear cell endometrial cancer as well as certain types of uterine sarcoma. Uterine cancer involving these cell types may require additional therapy beyond surgery.

The prognosis and treatment approach for uterine cancer is heavily dependent on the extent of spread of cancer (stage) and the aggressiveness of the tumor (cell type and grade). Advanced-stage, high-grade uterine cancer is typically associated with poorer prognosis and more aggressive treatment. Therefore, understanding the stage and grade of uterine cancer will help you make a more informed decision about your treatment plan.