The most important factor in predicting the current state of a man’s prostate cancer and determining his treatment options is his Gleason score. This method of grading a tumor’s aggressiveness was devised in the 1960s by Dr. Donald Gleason, a pathologist at the Minneapolis Veterans Affairs Hospital.
In the years since, methods of diagnosing prostate cancer and doctors’ understanding of tumor behavior have changed. Although Dr. Gleason’s original scoring system has evolved to reflect those changes, a consensus is emerging that it’s time to modify the way a man’s prognosis is reported as well.
How a biopsy Gleason score is determined
Following a needle biopsy that is performed to diagnose prostate cancer, the biopsied tissue is sent to a laboratory, where a pathologist views it under a microscope, looking for abnormalities in the appearance of cells.
The Gleason scoring system today has three grades (patterns) that the pathologist can use to describe how far the cancer cells deviate from normal, healthy cells. Normal prostate cells form highly organized rings, with well-defined borders. In contrast, cancer cells (grades 3 through 5) display various degrees of disorganization and distortion. Cancers whose cells appear closest to normal are considered grade 3 and generally are the least aggressive; those with more irregular, disorganized features are classified as grade 4 or 5 and generally are the most aggressive.
Classically, a man’s Gleason score is determined by adding the two most prevalent organizational patterns (grades) in the tumor together. For example, if the most common pattern-the primary grade-is 3 and the next most common pattern-the secondary grade-is 4, the Gleason score would be 3+4=7.
However, if the primary grade is 4 and the secondary grade is 3, the Gleason score would be 4+3=7. Although both sums are the same, 4+3 is more aggressive than 3+4, because the primary grade carries more weight than the secondary pattern in determining the aggressiveness of the cancer and the patient’s prognosis.
A third variable in the equation
In 2005, based on recommendations from an international group of experts, pathologists began to include the minor high-grade pattern (third most common) in the Gleason score when the specimen is from a radical prostatectomy or needle biopsy. In such cases, the highest Gleason score is important for determining prognosis. For example, in a needle biopsy core with 70 percent Gleason pattern 3, 25 percent pattern 4, and 5 percent pattern 5, the tumor would be graded as Gleason score 3+5=8, not 3+4=7. In radical prostatectomy specimens, there is a consensus that the term minor high-grade pattern should only be used when there are three grade patterns, such as with 3+4=7 or 4+3=7 with less than 5 percent Gleason pattern 5 at radical prostatectomy.
The rationale? Over the years, pathologists have found that a minor-component Gleason score that is higher grade than the second most common pattern influences prognosis. Including the least common (but highest grade pattern) improves the concordance between biopsy and radical prostatectomy specimens, and improves prediction of prognosis after surgery.
Prognosis: Perception vs. reality
In the past, Gleason scores were reported as 2 to 10 by adding grades of 1 to 5. Today, Gleason grades include only 3-5, and thus Gleason scores range from 6 to 10 by adding grades 3 to 5. Today, no man whose needle biopsy indicates cancer will receive a Gleason score of less than 6.
The problem is that many patients, when told they have a Gleason score 6 cancer, worry that their tumor, and thus their prognosis, is bad because the number 6 may be considered high. But doctors actually consider Gleason score 6 to be the lowest grade without the potential for metastatic spread, and with an excellent prognosis even without treatment. Some prostate cancer experts worry that this “mismatch” between perception and reality might lead a man to choose a more aggressive treatment than he really needs.
A Gleason score of 7 also poses a problem. The cure rate for a man with a Gleason score of 3+4=7 is more than 85 percent after surgery. But it drops to 65 to 70 percent for Gleason 4+3=7 cancer because there are more grade 4 cells. So while both of these cancers are Gleason 7, the numbers actually tell two very different stories-and are associated with two different prognoses.
Also, Gleason scores of 8, 9, and 10 are typically grouped together as high-grade cancers that are “bad” and “highly aggressive” and associated with the least favorable outlook. However, doctors now know that there is a difference in prognosis between these cancers. Indeed, approximately 60 percent of men with Gleason score 8 cancer have long-term disease-free intervals, compared with approximately 30 percent of those with Gleason score 9 and 10 cancers.
As a result of these insights, the International Society of Urological Pathology (ISUP) proposed classifying Gleason scores into the following five groups based on a man’s prognosis.
- Gleason grade group 1: Gleason score 6 (most favorable)
- Gleason grade group 2: Gleason score 3+4=7
- Gleason grade group 3: Gleason score 4+3=7
- Gleason grade group 4: Gleason score 8
- Gleason grade group 5: Gleason score 9 or 10 (least favorable)
At some hospitals, all biopsy results sent to patients now include their Gleason score and their prognostic grouping. Many prostate cancer experts believe that this information adds more clarity to the Gleason score, helping doctors and patients decide whether to start with active surveillance or pursue immediate treatment, and if so, what type. Case in point: The National Comprehensive Cancer Network (NCCN) now incorporates grade group into its guidelines for determining which risk group a patient falls in. Experts predict that the practice is likely to become more widespread in time, especially since this change is supported by the World Health Organization.