The Gleason Score is the primary method used to grade the aggressiveness of prostate cancer, providing a measure of how abnormal the cancer cells appear compared to healthy cells. This system is applied to tissue samples obtained through a biopsy, where a pathologist examines the microscopic patterns of the tumor. The resulting score is one of the most significant pieces of information guiding a patient’s management and long-term outlook. This score is fundamental in classifying prostate cancer into risk groups, which ultimately dictates the necessity and intensity of treatment.
How the Gleason Grading System Works
The Gleason system assigns a grade from 1 to 5 based on the cellular patterns seen in the prostate tissue sample. Grade 1 indicates cancer cells closely resemble normal tissue, while Grade 5 signifies poorly differentiated and highly disorganized cells, indicating greater aggressiveness. Grades 1 and 2 are rarely reported in modern practice, meaning the lowest score typically seen is 6.
To determine the final Gleason Score, the pathologist identifies the two most prevalent patterns of cancer cell growth within the biopsy sample. The grade of the most predominant pattern is the primary grade, and the grade of the second most prevalent pattern is the secondary grade. These two grades are then added together to produce a total score ranging from 6 to 10.
The order of the grades is informative, as the first number represents the dominant cellular characteristic of the tumor. For instance, a score of 4+3=7 suggests a more aggressive tumor than a score of 3+4=7, even though the total score is the same. The final score reflects the tumor’s heterogeneity, or the presence of different grades of cancer cells within the same area.
Defining a Gleason Score of 8
A Gleason Score of 8 is categorized as high-grade prostate cancer, signaling a tumor with poorly differentiated cells and a heightened potential for rapid growth and spread. This score places the cancer into Grade Group 4 under the newer, simplified grading system.
The score of 8 can arise from three combinations of primary and secondary grades: 4+4, 5+3, or 3+5. The 4+4 combination, which is the most frequent presentation, means both patterns are Grade 4, indicating moderately to poorly differentiated cells and aggressive cellular architecture.
Both 5+3 and 3+5 scores contain a Grade 5 pattern, which is the most abnormal and aggressive cell type. The presence of any Grade 5 cells, even as the secondary pattern, significantly contributes to the tumor’s biological aggressiveness and risk of recurrence. These high-grade cells have lost nearly all resemblance to healthy prostate tissue, suggesting they are more likely to escape the prostate capsule.
The distinction between combinations is prognostically relevant; studies indicate that 5+3 is generally more aggressive than 4+4, which is more aggressive than 3+5. However, any Gleason 8 tumor is considered a high-risk disease requiring aggressive therapeutic intervention. The score indicates a significant loss of cellular organization, which correlates directly with an increased propensity for metastasis.
Risk Stratification and Prognosis
The Gleason Score of 8 is sufficient on its own to classify a patient with localized disease into the “High-Risk” category. This classification is also determined by combining the Gleason Score with the serum Prostate-Specific Antigen (PSA) level and the clinical tumor stage (T-stage). High-risk criteria are met if the PSA is greater than 20 ng/mL, or if the cancer is locally advanced (T3).
This high-risk classification carries a more guarded prognosis, primarily due to the increased likelihood of the cancer having extended beyond the prostate capsule (extra-prostatic extension) or having spread to the lymph nodes. The cancer is aggressive and has a higher chance of recurrence following treatment compared to low- or intermediate-risk cancers.
For patients with a Gleason 8 tumor, the outlook requires aggressive management and vigilant monitoring. The prostate cancer-specific mortality rate at 10 years can range significantly, such as 19% for a 3+5 combination versus 44% for a 5+3 combination, highlighting the difference the sub-patterns make. This classification necessitates a multi-modality approach to maximize the chance of a successful long-term outcome.
Treatment Pathways for High-Grade Disease
The aggressive nature of a Gleason 8 tumor mandates a curative-intent, multimodal treatment strategy, meaning a combination of therapies is often recommended. Active surveillance, common for low-grade cancers, is not appropriate for Gleason 8 disease due to the high risk of progression and spread.
The two primary local treatment options are Radical Prostatectomy and External Beam Radiation Therapy (EBRT).
Radical Prostatectomy
Radical Prostatectomy involves the surgical removal of the entire prostate gland, seminal vesicles, and often a pelvic lymph node dissection to accurately stage the disease. This procedure is frequently chosen for younger, healthier patients with localized, high-grade cancer.
External Beam Radiation Therapy (EBRT)
External Beam Radiation Therapy delivers high-energy beams to the prostate from outside the body. For high-risk disease, EBRT is almost always combined with Androgen Deprivation Therapy (ADT). ADT, or hormone therapy, lowers male hormones like testosterone, which fuels prostate cancer growth, making the radiation more effective. This combination therapy typically involves ADT lasting for 18 to 24 months.
The combination of systemic therapy, such as ADT, with local treatments like surgery or radiation, is the standard of care for Gleason 8 tumors. This approach treats both the primary tumor and any microscopic cancer cells that may have already left the prostate. For patients undergoing radical prostatectomy, there is a significant chance (30% to 50%) that salvage radiation therapy may be required after surgery due to persistent or rising PSA levels.