Do you want to know what a prostate tissue specimen looks like when I view it under my microscope? Imagine looking at an abstract painting, with its countless shades and variations of color all swirled together on the canvas. Within this mass on my biopsy slide are normal cells and, in some cases, cells that are not normal. By viewing this sample, I am able to determine if cancer is present and, if so, how much.
What I am looking at are specific patterns of the cells from the part of the prostate that produces seminal fluid and the proteins within it. Prostate cancers arise in this part of the gland. When prostate cancer is present, the cellular configurations are altered and can be divided into five recognizable patterns that are added together to form a score.
A look at the Gleason score
Donald F. Gleason, M.D., Ph.D., first described the five patterns in the 1960s, when he served as chief of pathology at the Minneapolis VA Medical Center. He devised a method of ranking them that bears his name: the Gleason score. This prostate cancer grading system is still the most accurate predictor of the cancer’s aggressiveness and is used widely to guide cancer management. The higher the Gleason score, the more virulent the prostate tumor tends to be.
There are five Gleason patterns, or grades, from 1 through 5, which describe the extent of gland alteration. Grades 1 through 3 describe glandular patterns that appear more normal and orderly, whereas grades 4 and 5 describe cell patterns that appear chaotic. Glandular patterns of 1, 2, and 3 are associated with a more benign clinical course, while grades 4 and 5 tend to behave aggressively and spread beyond the prostate.
Prostate cancer cells are often made up of an array of grades, some of which appear to be fairly normal and others quite disorderly. Gleason discovered that by adding the two most prevalent grades together to arrive at a score, and tumor aggressiveness could be predicted with a high degree of precision.
For example, if the most prevalent, or primary, glandular grade seen is 3, and the second most prevalent, or secondary, grade is 4, the Gleason score would be 3 + 4 = 7, with 3 the primary and 4 the secondary grade. However, if the most prevalent grade is 4, and the second most prevalent grade is 3, then the Gleason score would also equal 7 (4 + 3), but with 4 the primary grade and 3 the secondary grade. The tumor that is scored 3 + 4 behaves less aggressively than the 4 + 3 tumor because the primary pattern is 3 rather than 4.
To complicate matters further, pathologists have decided to abbreviate the Gleason grading system, and only scores of 3, 4, and 5 are used to describe prostate biopsies for both primary and secondary grades; these are added up to obtain scores from 6 through 10. Gleason score 6 cancers tend to behave less aggressively than Gleason score 7 cancers, which, in turn, behave less aggressively than cancers scored as 8, 9, and 10.
Today, 60 percent to 70 percent of cancers diagnosed on a prostate biopsy are graded as Gleason score 6; about 20 percent to 30 percent are Gleason score 7; and 5 percent to 10 percent are Gleason score 8 and higher. The vast majority of cancers picked up on a prostate biopsy are the least aggressive type. As you might expect, assigning higher grades contributes to the higher rates of prostate cancer treatment.
The new prostate cancer grading system
The Gleason prostate cancer grading system, which has 25 possible scores, has been confusing to many doctors and patients, and this has led to unnecessary treatment of prostate cancer. This is why I, along with other researchers, have created a new five-grade system that is easier to use and
understand, but also more accurate than the Gleason system, with only five possible scores. The new prostate cancer scoring system has the potential to substantially reduce overtreatment of low-risk cancer.
The five-grade system is based on an analysis of 2013 data from more than 7,000 prostate cancer patients at The Johns Hopkins Hospital. To verify the accuracy of the new stratification, we also analyzed data obtained from tissues of more than 20,000 men whose prostates had been surgically removed between 2005 and 2014 at Hopkins and four other medical institutions. We also included data from biopsies of more than 5,000 men treated with radiotherapy at two medical centers during the same period.
A better predictor?
The results suggested that the prognostic discrimination for the new grading system was higher than the most commonly used combinations of the Gleason scores. For example, the original Gleason system typically considers Gleason score 7 as requiring radiation therapy. However, the new system broke up Gleason 7 into Grade Group 2 and Grade Group 3, in which 3’s prognosis is twice as bad as 2’s.
The difference in Grade Groups is especially critical for selecting a therapy. For example, Grade Group 3 is treated with hormonal therapy in addition to radiation, which carries significant side effects, whereas Grade Group 2 is treated only with radiation. Similarly, the Gleason scores 8 to 10 are typically considered one grade, yet in the new prostate cancer grading system, these grades can be split into Grade Group 4 and Grade Group 5, where, again, Grade 5 is twice as aggressive.
When we looked at our study data, 40 percent of the men in the study fell into either Grade Group 2 or 3 and would be affected by distinguishing between the two, and 10 percent of the men fell into either Grade Group 4 or 5. Therefore, by using the new system, 50 percent of the men in the study would have received a more appropriate treatment than if their doctors had used the most common combinations of the Gleason score.
A major plus of the new grading system is that it will reduce overtreatment of prostate cancer that develops slowly by allowing more rational, less emotional decision-making. Men who are assigned Grade Group 1 will know that their cancer has no metastatic potential. This should also reassure men in this group who choose active surveillance.
The World Health Organization has now recommended that the new prostate cancer grading system be used worldwide. Change doesn’t come quickly in the medical world, but I am confident that over time this new grading system will be widely adopted internationally.
Jonathan I. Epstein, M.D., is a professor in the departments of pathology, urology, and oncology at Johns Hopkins Medicine and the Reinhard Professor of Urologic Pathology at Johns Hopkins Medical Institutions. He is also director of surgical pathology at Johns Hopkins Hospital.