The grading of prostate cancer measures how aggressive tumor cells appear under a microscope, which predicts the cancer’s potential behavior. A pathologist examines a tissue sample, typically from a biopsy, to determine how closely cancer cells resemble normal prostate cells. A higher grade indicates that the cells are more abnormal and are more likely to grow and spread quickly. This grading allows physicians to assess the risk level of the disease and guide the patient toward the appropriate management plan.
Understanding the Traditional Gleason Score
The original method for grading prostate cancer was the Gleason scoring system, developed in the 1960s by pathologist Donald Gleason. This system assigned a grade from 1 (resembling normal tissue) to 5 (highly abnormal) based on the architectural pattern of the cancer cells. The final score was calculated by adding the primary (most common) pattern grade to the secondary (second most common) pattern grade.
For instance, a tumor where the most common pattern was Grade 3 and the second most common was Grade 4 resulted in a Gleason Score of \(3+4=7\). In modern practice, scores lower than 6 are almost never assigned, meaning the practical range for a Gleason Score is 6 to 10.
The initial grade (the first number) is the most significant because it represents the dominant cell type. A Gleason Score of \(4+3=7\) is considered more aggressive than a score of \(3+4=7\), even though the total sum is the same. The \(4+3=7\) designation indicates that the more aggressive Pattern 4 cells are the most prevalent.
Why the Grading System Needed an Update
The traditional Gleason Score caused confusion for patients and clinicians due to several limitations. The lowest possible score was 6, which often led patients with the least aggressive cancer to mistakenly believe their disease was halfway up a 10-point scale. This sometimes resulted in patients opting for unnecessary immediate treatment instead of less invasive options like active surveillance.
The system also failed to adequately distinguish between different prognostic groups, especially in the intermediate range. Although scores of \(3+4=7\) and \(4+3=7\) were mathematically identical, their clinical outcomes were significantly different. This lack of precision prompted the International Society of Urological Pathology (ISUP) to develop a more intuitive and prognostically accurate system.
to the New Grade Group System
The new system, officially adopted by the World Health Organization (WHO) in 2016, is called the Grade Group (GG) system. This system simplifies risk stratification by compressing the range of possible Gleason Scores into five distinct Grade Groups, numbered 1 through 5. These groups correspond directly to increasing cancer aggressiveness and risk.
Grade Group 1 represents the lowest-risk prostate cancer and is assigned only to a Gleason Score of 6 (\(3+3\)). This re-designation eliminates patient anxiety associated with the number 6 by establishing it as the most favorable outcome. Grade Group 2 is assigned to the intermediate-risk score of \(3+4=7\), where the less aggressive pattern remains dominant.
Grade Group 3 is assigned to the intermediate-risk Gleason Score of \(4+3=7\), where the more aggressive Pattern 4 is most prevalent. This separation of the two score 7 cancers reflects their different prognoses. Grade Group 4 is assigned to tumors with a Gleason Score of 8, including \(4+4=8\), \(3+5=8\), or \(5+3=8\).
The highest-risk cancers, those with a Gleason Score of 9 or 10, are placed into Grade Group 5. This 1 to 5 scale provides a more accurate representation of the cancer’s biological behavior. The five Grade Groups have demonstrated a better ability to predict outcomes compared to the older system.
How Grade Groups Influence Treatment Decisions
The Grade Group system translates pathology findings directly into clinical management strategies. For individuals diagnosed with Grade Group 1, which is the least aggressive disease, treatment often involves active surveillance. This approach requires regular monitoring using tests like PSA checks and repeat biopsies. Definitive treatment is only initiated if the cancer shows signs of progression.
Cancers classified as Grade Group 2 or Grade Group 3 are considered intermediate-risk, and management may involve a more active approach. Treatment options include surgery, such as radical prostatectomy, or radiation therapy. The decision between surveillance and active treatment in these intermediate groups is personalized. Factors considered include the patient’s age, overall health, and preferences.
For patients with Grade Group 4 or Grade Group 5, the disease is high-risk. Immediate, aggressive treatment is usually warranted because these cancers have a higher likelihood of growth and spread. Therapies may combine external beam radiation with hormone therapy, or radical surgery, often including the removal of nearby lymph nodes. The Grade Group guides the clinical conversation and treatment pathway for prostate cancer patients.