Dr. Paul Nguyen explains how clinicians integrate risk stratification following a patient's diagnosis results.
Dr. Paul Nguyen explains how clinicians integrate risk stratification following a patient's diagnosis results.
Dr. Paul Nguyen explains how clinicians integrate risk stratification following a patient's diagnosis results.

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.

Zachary Klaassen, MD, MSc
Urologic Oncologist, Georgia Cancer Center, Augusta University, Augusta, GA, USA