For men who are diagnosed with prostate cancer, one of the most important parts of planning treatment is understanding how aggressive the cancer is and how far it has spread. While many people are familiar with the idea of cancer stages (ranging from 1 to 4), prostate cancer risk stratification is somewhat more nuanced.
Most men who are diagnosed with prostate cancer initially have an elevated PSA blood test, which then leads to a prostate biopsy, with or without an MRI (magnetic resonance imaging) test before the biopsy. It is this biopsy that the doctor uses to make the prostate cancer diagnosis. At this time, using the information available, it is possible to provide a risk stratification. This process of risk stratification is done to group patients based on the likelihood that their cancer has— or will in the future—spread outside the prostate. This is important for determining which further tests may be required and which treatments are most appropriate.
There are several tests that can be used to divide men with localized cancer into groups following their initial diagnosis. These tests include the results of the biopsy, the PSA blood test from before the biopsy, and the physical examination of the prostate. A pathologist looks at the biopsy and studies the microscopic appearance of the prostate cancer cells to provide a cancer grade or Gleason score, which is an important part of the risk stratification process.
Prostate cancer grade can be divided into five categories (called ISUP grade groups) ranging from 1 to 5 (with 1 being the least aggressive and 5 being the most aggressive). These correspond to Gleason scores which range from 6 to 10 (with 6 being the least aggressive and 10 being the most aggressive). PSA levels are grouped into three categories: less than 10ng/mL, 10-20ng/mL, and more than 20 ng/mL. Finally, the results of the digital rectal examination (DRE) may show that the cancer can’t be felt, that the cancer is relatively small and contained within the prostate, has grown outside the prostate, or has grown into nearby structures (such as the bladder, pelvis, or rectum).
These three characteristics are then combined to provide risk stratification. There are many different ways to do this that have been proposed including D’Amico risk groups, the AUA classification, and the NCCN classification.
Very Low and Low-Risk Disease
Patients who have low-grade (ISUP 1 or Gleason score 6) cancers, PSA less than 10, and either a tumor that can’t be felt or can be felt but is small and restricted to the prostate have low-risk disease. When there is only a very small amount of cancer seen on the biopsy, a urologist may deem that a patient has a very low-risk disease. These patients don’t typically require any further tests and may be recommended for active surveillance. Details of active surveillance are discussed in another article.
Intermediate Risk Disease
If you have any of one or more of the following intermediate risk factors, you have intermediate-risk disease: ISUP grade 2 or 3 cancer on biopsy, a PSA between 10 and 20 ng/mL, or a greater extent of cancer on digital rectal examination (cT2b-c). Patients with intermediate-risk disease may be further subdivided into favorable or unfavorable intermediate-risk disease based on the number of these factors and the number of biopsy samples that showed cancer. For many patients with intermediate-risk disease, there is a chance that the cancer has spread outside the prostate. Therefore, so-called staging investigations—imaging tests— may be performed to find out if the cancer has spread. These imaging tests may include a bone scan, a CT (computed tomography), an MRI (magnetic resonance imaging), or PET (positron emission tomography) scan. Details about each of these tests are provided in separate articles. When these tests show no evidence that the cancer has spread, men with intermediate-risk prostate cancer are typically recommended to undergo treatment with either surgery or radiotherapy, though observation may be appropriate for some men (i.e., those with other health problems and favorable intermediate-risk disease).
High Risk Disease
Finally, men with any of the following: a PSA score above 20ng/mL, ISUP grade 4 or 5 cancer on biopsy, or evidence on physical examination that the cancer has spread outside the prostate, are deemed to have high-risk disease. These men should undergo staging investigations as detailed above as they have a higher risk of cancer spreading outside the prostate. Most men with high-risk disease end up needing a combination of treatments including surgery, radiotherapy, and hormone therapies.
When staging investigations show the spread of cancer to lymph nodes (either nearby in the pelvis or elsewhere in the body), to the bones, or to other organs this means patients have regional or metastatic involvement. While local prostate cancer treatments are sometimes appropriate in this situation, the mainstay of treatment is systemic therapy with hormone treatments.
In summary, risk stratification is key for men newly diagnosed with prostate cancer. This is performed using information from the biopsy (tumor grade), the PSA blood test, and physical examination. Risk stratification is key to guiding further staging and appropriate treatments.
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.