Prostate Cancer Staging: The Four Stages, TNM, PSA and Gleason score

Key takeaways

• Diagnosis is the first step to determining if a person has prostate cancer. This is often followed by prostate cancer staging to help ascertain the severity of the condition.
• Prostate cancer stages are grouped into four—from I-IV. The TNM staging system, PSA test, and Gleason Score are the parameters used to determine a person‘s prostate cancer stage. 
• A combination of results from these parameters describes the tumor size and its extent of spread to other parts of the body. It also tells the doctor what to expect from a patient's condition and predicts the outcome of treatment.

Prostate cancer staging is the process of determining the extent of prostate cancer disease, where the cancer cells are located, and how far they’ve spread in the body. It helps to assess the level of damage cancer has done.

Current prostate cancer staging is based on the American Joint Committee on Cancer’s (AJCC) Cancer Staging Manual. In its 8th edition, The Cancer Staging Manual aimed for a more personalized than population-based approach to cancer staging. This means that an individual's information is used to stage his cancer, rather than generalizing the process.

To determine the stages of prostate cancer, these elements of the AJCC’s system are considered: 

• the TNM staging system
• the Prostate-Specific Antigen (PSA) levels
• the Gleason Prostate Cancer Score

However, doctors diagnose prostate cancer before staging it. 

Diagnosis of prostate cancer

Diagnosis is an assessment of a patient's symptoms to identify his illness. A prostate cancer diagnosis tells you whether cancer cells are present or absent in the prostate. Thereby providing information as to whether someone has prostate cancer or not.  

There are three primary ways doctors often make a prostate cancer diagnosis:

1. Digital Rectal Examination (DRE)
2. Protein-Specific Antigen (PSA) test
3. Tissue Biopsy

The PSA test is specifically important for doing prostate cancer staging.

Prostate-specific antigen (PSA) test

The prostate gland produces a protein known as protein-specific antigen (PSA). PSA is present in the semen and also, in the blood. A PSA test checks for the level of this protein in the blood. A high level of PSA indicates a prostate-related medical condition. This condition might be prostate cancer, benign prostate hyperplasia (BPH), inflammation, or infection of the prostate.

A PSA level of 4 ng/mL or less means the prostate is normal. Above 4 ng/mL means the patient requires further testing. From 4ng/mL to 10ng/mL there is a 25% chance of prostate cancer. Above 10ng/mL, has a 50% chance of being prostate cancer.

See the table below:

To understand how prostate cancer is staged, it's also important to talk about the TNM staging system and the Gleason score first.

The TNM staging system

The TNM system is the most commonly used system for prostate cancer staging. (7) TNM stands for T (Tumor size), N (Lymph nodes), and M (metastasis).

The T category describes the size of the main tumor in the prostate. T is divided into Tx, T0, T1, T2, T3, and T4.

• Tx = the tumor cannot be evaluated
• T0 = there’s no evidence of tumor
• T1 = tumor is present, but it’s too little to be seen or felt. T1 is subdivided into T1a, T1b, and T1c. T1a = cancer is in less than 5% of the tissue;   T1b = cancer is in more than 5% of the tissue; T1c = cancer is very present 

• T2 = the tumors are inside and can be seen within the prostate. T2 is subdivided into T2a, T2b, and T2c. T2a = the tumor is in one-half of one lobe of the prostate; T2b = the tumor is in more than one-half of one lobe of the prostate; T2c = the tumor is in both lobes of the prostate;

• T3 = the tumor is beyond the outer covering of the prostate called the prostate capsules. T3 is subdivided into T3a and T3b. T3a = the tumor has broken the prostate capsule; T3b = the tumor has spread into the neighboring seminal vesicles
• T4 = the tumor has spread to the adjacent body organs like the bladder, rectum, and pelvic wall. It has no subdivision.

The N category explains whether prostate cancer has spread to surrounding pelvic lymph nodes or not. Lymph nodes are tiny cell structures that filter and destroy disease-causing foreign bodies entering an organ. 

The N category is divided into Nx, N0, and N1.

• Nx = the pelvic lymph nodes cannot be evaluated.
• N0 = there are no cancer cells in the pelvic lymph nodes.
• N1 = there are cancer cells in the pelvic lymph nodes.

The M category explains the level to which cancer has spread to other parts/organs of the body. M is divided into Mx, M0, and M1.

•  Mx = Metastatic cancer cannot be evaluated
• M0 = there’s no spread of cancer to other parts of the body
• M1 = there’s a spread of cancer to other parts of the body. It is subdivided into M1a, M1b, and M1c. M1a = cancer spreads to the lymph nodes outside the pelvis; M1b = cancer spreads to the bone; M1c = cancer spreads to other parts of the body like the lungs.

Gleason score

Dr. Donald Gleason developed the Gleason Score in the 1960s. It tells the severity of cancer based on the appearance of the tissue samples under the microscope. It grades cancer on a scale of 1 – 5 based on how cells change from normal to cancerous. Grade 1 cells look normal, while Grade 5 cells are mutated and do not look normal.

For each patient, the doctor assigns two grades to the cancer cells. The first shows the predominant grade, while the second shows the less predominant grade. 

For example, a patient can have two grades of 5 and 4. These two grades add up to give the Gleason Score. Hence, 5 + 4 = 9. So, the patient has a Gleason Score of 9. 

The least possible Gleason Score is 2 (1 + 1), and the highest Gleason Score is 10 (5 + 5).

In 2014, however, the International Society of Urological Pathology (ISUP) reviewed and updated the Gleason Score. This was because of the shortfalls most doctors observed while handling cancer patients. Patients hardly recorded a Gleason Score of 2 – 5, because of a high level of cancer spread upon diagnosis. Gleason scores between 6 and 10 were the most common. Hence, 6 became the low grade, 7 was the intermediate grade, and 8 to 10 were the high grades.

• 6 = low grade;
• 7 = Intermediate grade; and 
• 8 – 10 = High grade. 

Also, the Gleason score was not always accurate in predicting the severity of cancer, and how patients responded to treatment. This mostly happened with the Gleason Score of 7, which was a combination of either (4 + 3) or (3 + 4). Grade 4 cells were more deformed and aggressive than Grade 3 cells. Patients with a Gleason score of 7 (4 + 3) were managed differently from patients with a Gleason Score of 7 (3 + 4). This became a major source of concern.         

So, ISUP formed a new grading system that was simpler and clearer. They called it the Grade Groups. 

Grade groups classified cancer cells into five groups based on their Gleason Score and placed them into risk groups.

See the table below:

The stages of prostate cancer

As explained earlier, these parameters are considered in determining a patient’s stage of prostate cancer: the T, N, and M categories, the PSA levels, and the Gleason Score (Grade Group). Each stage combines and uses the results from these parameters. 

There are four stages of prostate cancer: I, II, III, and IV. However, Stages II, III, and IV have subdivisions, bulking the stages up to nine. Hence, the stages are I, IIA, IIB, IIC, IIIA, IIIB, IIIC, IVA, and IVB.

The table below shows the different stages, their combination of results using the parameters—TNM, PSA level, and Gleason score, and the location of cancer. 

Stage I prostate cancer

This stage is characterized by values of T at T1, T2 (T2a), N at N0, M at M0, a PSA level below 10 ng/mL, and a Group Grade of 1. At this stage, the tumor is perfectly contained in the prostate by the prostate capsules. And it hasn't spread to the lymph nodes and other parts of the body. There's a 25% chance the patient has prostate cancer, so they fall under the low-risk group.

Stage II prostate cancer

This stage is subdivided into IIA, IIB, and IIC. They're characterized by values of T at T1, T2 (T2a, T2b & T2c), N at N0, M at M0, a PSA level above or equal to 10ng/mL, but less than 20 ng/mL, and a Group Grade of 1. The tumor is still contained in the prostate and has not spread to the lymph nodes and other parts of the body. There's a 50% chance the patient has prostate cancer, and so falls under the intermediate risk group.

Stage III prostate cancer

This stage is subdivided into IIIA, IIIB, and IIIC. They're characterized by values of T at T1, T2, T3, and T4, N at N0, M at M0, a PSA level greater than 20 ng/mL, and a Group Grade of 1–5. At this prostate cancer stage, the tumor has broken through the prostate capsules into the nearby tissues, like the bladder. It has also spread to the lymph nodes and other parts of the body. There's more than a 50% chance that the patient has prostate cancer, and so falls under the high-risk group.

Stage IV prostate cancer

This is the last stage of prostate cancer and is subdivided into IVA and IVB. They're characterized by values of T at T1, T2, T3, and T4, N at N0 and N1, M at M0 and M1, a PSA level above 20 ng/mL, and a Group Grade of 1 - 5. The tumor at this stage has spread beyond the prostate into the lymph nodes and other organs of the body. The test results at this stage will show that the patient has prostate cancer and is in the very high-risk group.

Wrap up

At the initial stages, prostate cancer shows little to no symptoms. Most symptoms show up at the later stages. And that's why prostate cancer is mostly detected late. Some of the symptoms include painful urination, blood in the semen, and fatigue.

Knowing the stages of prostate cancer is a key factor in choosing a treatment plan. There are many available treatment options for prostate cancer. They include chemotherapy, surgery, immunotherapy, and the use of the vaccine Provenge. The doctor, with his team of professionals, chooses a treatment plan in agreement with the patient. 

Go for regular prostate cancer screening and ask your doctor questions about prostate cancer. This will help you know when you develop cancer, the stage of prostate cancer, and what to do about it.