What Informs Your Treatment Options

Understanding Prostate Cancer Risk Groups

If you have been diagnosed with prostate cancer, the next step is finding out how aggressive (fast-growing) the cancer is and if it has spread beyond the prostate.

Many people are familiar with cancer stages (Stages 1 through 4). Prostate cancer is also grouped by risk level. This is called risk stratification.

Knowing your risk group helps your healthcare team decide:

  • If you need more tests
  • Which treatment options may be best for you
  • How likely the cancer is to grow or spread

How Is Prostate Cancer Risk Determined?

Most men are diagnosed after:

  • A higher-than-normal PSA (prostate-specific antigen) blood test result
  • A prostate biopsy
  • Sometimes an MRI before the biopsy

A biopsy confirms if the cells are cancer. The information from the biopsy, along with other test results, is used to place the cancer into a risk group.

Your healthcare provider looks at three main factors:

Together, these help estimate how likely the cancer is to spread outside the prostate.

Biopsy Results

A pathologist examines the biopsy samples under a microscope to see how abnormal the cancer cells look. This is called the grade of the cancer.

The grade may be reported as:

  • ISUP Grade Group 1 to 5. Grade Group 1 is the least aggressive. Grade Group 5 is the most aggressive.
  • Gleason score. The scores range from 6 to 10. A Gleason score of 6 is the least aggressive. A score of 10 is the most aggressive.

Higher grades mean the cancer is more likely to grow and spread.

PSA Level

Your PSA blood test also helps determine your risk group.

PSA levels are generally divided into three ranges:

  • Less than 10 ng/mL
  • 10 to 20 ng/mL
  • More than 20 ng/mL

Higher PSA levels may suggest a greater chance that the cancer has grown beyond the prostate.

Digital Rectal Exam (DRE)

During a digital rectal exam, your healthcare provider gently feels the prostate through the rectum.

The exam may show that:

  • The cancer cannot be felt.
  • The cancer is small and appears to be only in the prostate.
  • The cancer may have grown outside the prostate.
  • The cancer may have spread into nearby tissues, such as the bladder, pelvis, or rectum.

How Risk Groups Are Created

Healthcare providers combine these to place your cancer into a risk group:

  • Biopsy grade
  • PSA level
  • Digital rectal exam findings

Several systems are used to classify prostate cancer risk. These include the D'Amico, American Urological Association (AUA), and National Comprehensive Cancer Network (NCCN) systems. Although these systems differ slightly, they all help guide treatment decisions.

Very Low- and Low-Risk Prostate Cancer

Low-risk prostate cancer usually includes:

  • Cells that are ISUP Grade Group 1 (Gleason score 6)
  • PSA less than 10 ng/mL
  • Cancer that cannot be felt or is small and confined to the prostate

Some men have only a very small amount of cancer found on their biopsy. They may be classified as having very low-risk prostate cancer.

People with very low- or low-risk prostate cancer usually do not need additional imaging tests. Many are good candidates for active surveillance. This means closely monitoring the cancer with regular checkups instead of treating it right away.

Intermediate-Risk Prostate Cancer

Intermediate-risk prostate cancer is when you have one or more of these:

  • Cells that are ISUP Grade Group 2 or 3
  • PSA between 10 and 20 ng/mL
  • Cancer that is larger but still appears to be only in the prostate on a digital rectal exam

Intermediate-risk prostate cancer may be described as favorable or unfavorable. This depends on factors such as:

  • How many intermediate-risk features it has
  • How many biopsy samples have cancer cells

Some men with intermediate-risk prostate cancer will need imaging tests to check if the cancer has spread.

These tests may include:

  • Bone scan
  • CT scan
  • MRI
  • PET scan

If the cancer has not spread, treatment is often recommended. This may include:

  • Surgery
  • Radiation therapy

For some men - especially those with other serious health conditions or favorable intermediate-risk disease - active surveillance may also be an option.

High-Risk Prostate Cancer

High-risk prostate cancer includes any of the following:

  • Cells that are ISUP Grade Group 4 or 5
  • PSA greater than 20 ng/mL
  • Signs on a digital rectal exam that the cancer has grown outside the prostate

People with high-risk prostate cancer usually need imaging tests to look for signs that the cancer has spread.

Treatment often involves more than one approach, such as:

  • Surgery
  • Radiation therapy
  • Hormone therapy

If the Cancer Has Spread

Sometimes imaging tests show that prostate cancer has spread to any of these:

  • Nearby lymph nodes
  • Lymph nodes in other parts of the body
  • Bones
  • Other organs

This is called regional or metastatic prostate cancer.

Some men may still benefit from treatment directed at the prostate. However, treatment usually focuses on systemic therapy, such as hormone therapy. Hormone therapy for this stage is usually combined with other medications, such as newer hormone-blocking drugs or chemotherapy, rather than used alone. Systemic treatments travel throughout the body to treat cancer cells wherever they may be.

Talking with Your Healthcare Team

Risk stratification helps your healthcare team understand how likely your prostate cancer is to grow or spread. Knowing your risk group helps guide decisions about:

  • If you need more imaging tests
  • Which treatments may be best for you
  • If active surveillance may be an option

Talk to your healthcare team if you are unsure about any test results, or you need to ask more questions.

One of the most important steps in your cancer diagnosis process is finding out your prostate “cancer stage.”  Knowing your stage of prostate cancer guides your doctor’s  decisions about which treatment is appropriate for you.  It also provides important information regarding the expected long-term outcomes and survival rates.

Once you are diagnosed with prostate cancer, your doctor may need to perform a test known as a prostate biopsy to see if your cancer has spread and to find out your cancer stage. A prostate biopsy means that small samples of the prostate tissue are removed with a needle and then examined under a microscope. This test will determine your Gleason score and Grade Group. Your PSA level at the time of diagnosis is also important for risk stratification.

Your PSA blood test result and tumor grade on biopsy (the microscopic appearance of the cancer cells from a prostate biopsy) will help your doctor determine the risk of your cancer spreading. Then your doctor will decide if you need additional imaging tests (i.e., CT scan, bone scan, prostate MRI, PSMA PET/CT scan, etc.) to find out if the tumor has spread. For men with very-low and low-risk tumors, the chance of spread is so low that additional tests are not usually needed. However, for men with more aggressive tumors, staging tests are typically recommended.

The most common and well-known staging system of cancers is the American Joint Committee on Cancer (AJCC) TNM system, which was updated most recently for prostate cancer in 2018.

Staging of prostate cancer is based on three categories:

  • T category: the size of the primary tumor
  • N category: the spread of cancer to the lymph nodes
  • M category: whether cancer has spread to other parts of the body

The clinical T stage (noted by the letter “c”) represents how far the tumor in the prostate has grown based on a clinical evaluation. This is mostly based on a physical examination by your doctor (the “digital rectal examination”). However, information from prostate MRI and prostate biopsy may also be helpful.

During stage 1, many tumors cannot be felt or are detected incidentally during other prostate procedures (like a transurethral resection of the prostate). Others may be felt but are contained within the prostate (stage T2). Still others may be felt but may have grown beyond the prostate (stage T3 and T4).

A pathologic T stage (noted by the letter “p”) is assigned for patients that have had their prostate removed. It is based on the microscopic examination by a pathologist (typically more accurate than clinical T stage).

The “N stage” refers to the involvement of lymph nodes in the pelvis. Clinical N stage is typically assigned based on results of a CT scan, MRI, or PSMA PET/CT scan, which may find enlarged lymph nodes suspicious for cancer spread. Pathologic N stage is based on examination of lymph nodes that are removed at the time of prostatectomy.

Finally, the “M stage” refers to metastasis, or spread, to other parts of the body including lymph nodes outside the pelvis, the bones, and other organs. Clinical M stage is based on imaging tests such as bone scan, CT scan, MRI, or PSMA PET/CT scan. Pathologic M stage can be confirmed by biopsy of a metastatic site but this is not often required.

Higher T, N, and M stages are associated with more advanced prostate cancer, and in combination with PSA and Gleason Group, help assign stage grouping from I to IV.

The Stages of Prostate Cancer:

Stage I

  • cT1N0M0 (the tumor cannot be felt and is not seen on ultrasound imaging), Grade Group 1 (Gleason score 6 or less), PSA less than 10 ng/mL, OR
  • cT2aN0M0 (the tumor is felt or seen in one half or less of one side of the prostate gland), Grade Group 1, PSA less than 10 ng/mL, OR
  • pT2N0M0 (the prostate is removed and the tumor is only in the prostate gland), Grade Group 1, PSA less than 10 ng/mL

Stage IIA

  • cT1N0M0, Grade Group 1, PSA less than 10-20 ng/mL, OR
  • cT2a or pT2N0M0, Grade Group 1, PSA less than 10-20 ng/mL, OR
  • cT2b or cT2cN0M0 (the tumor is felt or seen in more than half of one side [cT2b] or both sides [cT2c] of the prostate gland), Grade Group 1, PSA less than 20 ng/mL

Stage IIB

  • T1 or T2N0M0, Grade Group 2 (Gleason score 3+4=7), PSA less than 20 ng/mL

Stage IIC

  • T1 or T2N0M0, Grade Group 3 or 4 (Gleason score 4+3=7 or Gleason score 8), PSA less than 20 ng/mL

Stage IIIA

  • T1 or T2N0M0, Grade Group 1 to 4 (Gleason score 8 or less), PSA at least 20 ng/mL

Stage IIIB

  • T3 or T4N0M0 (the cancer has grown outside the prostate gland and may have spread to the seminal vesicles ([T3], or surrounding structures such as the bladder or rectum [T4]), Grade Group 1 to 4, any PSA

Stage IIIC

  • Any TN0M0, Grade Group 5 (Gleason score 9 or 10), any PSA

Stage IVA

  • Any TN1M0 (the cancer has spread to nearby lymph nodes), any Grade Group, any PSA

Stage IVB

  • Any T, any N, M1 (the cancer has spread to other parts of the body such as distant lymph nodes, bones, or other organs [i.e., lungs, liver, etc.]), any Grade Group, any PSA               

Based on data from the SEER database (Survivor, Epidemiology, and End Results Program), the 5-year relative survival rate for localized prostate cancer (no disease outside the prostate, stages I-IIIA) and for regional disease (prostate cancer growing into nearby structures or lymph nodes, stages IIIB-IVA) is over 99%. The 5-year survival rate for distant metastasis (stage IVB) is 31%.

Ultimately, the staging of prostate cancer is complex and may be overwhelming to most patients. Each patient should ensure that their doctor explains their stage of prostate cancer and the implications of subsequent treatment.