Discovery
January 22, 2016

After all the worry — the elevated PSA, then the biopsy — the diagnosis is finally here. You just found out that you have prostate cancer and the Gleason score is a 3+3=6. What does that even mean? You look it up; the literature your doctor provided says that "the score is the sum of the most common and second-most common Gleason patterns." Apparently, the lowest score is 2 (1+1) and the highest is 10 (5+5) — and you are a 6. That looks like you're on the more significant end of the spectrum.

Wrong. Nobody gets a Gleason 2; they aren't ever diagnosed on needle biopsies. "In fact, Gleason 6 is as good as it gets," says urologist Patrick C. Walsh, M.D., University Distinguished Service Professor of Urology. It's not easy for most men to figure this out right away, because the way Gleason scores are are determined is just plain confusing – unless you're a pathologist, seeing how a bunch of cells look under the microscope, and noticing which two combined patterns of cells are most prevalent.

Brady pathologist Jonathan Epstein, M.D., the Rose-Lee and Keith Reinhard Professor of Urologic Pathology, wants to make it easier for men to understand their prostate cancer diagnosis. "Jonathan Epstein is unique in many ways, and one of them is that he does something that almost no other pathologist does – he actually talks to patients frequently," says Walsh. "He understands how confusing this system is for most people to understand, and he wanted to fix this problem." Epstein's new system, compared to the current Gleason system, is far simpler, with just five groups of cancer. One innovation is that it puts the confusing Gleason 7 score — which is very different, depending on whether it's 3+4 or 4+3 — into two different groups. As Epstein explains: "The current prostate cancer grading system was developed between 1966 and 1974 by Donald Gleason. The system assigns histological patterns 1 through 5, adding the most and second-most common patterns with Gleason scores ranging from 2 to 10. There are more than 25 different possible combinations with this system." Doctors and scientists have tried to fix this; the Gleason system was revised in 2005 and again in 2014. "The current application of Gleason grading differs dramatically from the original system," Epstein continues. "Scores 2 through 5 are no longer assigned and certain patterns that Gleason defined as a score of 6 are now graded as 7." But the Gleason 7 score itself is still pretty confusing: "A Gleason score 7 can represent mostly well-differentiated cancer, with a smaller component of more poorly differentiated cancer" — that would be Gleason 3+4=7 – "or mostly poorly differentiated cancer with a smaller component of well-differentiated cancer," the score of Gleason 4+3=7. "Another weakness of the Gleason system is that the lowest score is now assigned a 6, although it is on a scale of 2-10."

In a study of more than 25,000 men treated for prostate cancer at Hopkins and four other institutions, Epstein and colleagues verified a simplified system that cuts through the numbers. Epstein presented the new system at the 2015 meeting of the American Urological Association in New Orleans. "It's more accurate than the current Gleason system, with only five grades," Epstein says, "and the lowest grade is 1, as opposed to 6." This also has the potential to reduce overtreatment of indolent prostate cancer, he notes. "We hope that this will permit more rational and less emotional decision-making; that men who are assigned a Grade Group 1 out of 5 will know that their cancer has an indolent nature. Tumors that are a pure Grade Group 1 at radical prostatectomy have no metastatic potential."

This might also reassure men in this group who choose active surveillance. "Some men with Grade Group 2 tumors may also be candidates for active surveillance, or for radiation therapy instead of surgery depending on their age, extent of cancer, and general health." In addition to making a clear distinction between the two Gleason 7 scores, the system separates Gleason 8 cancer from Gleason 9 and 10 tumors. "Gleason scores 8-10 are usually combined," Epstein says. However, "although they are high-grade tumors, they still have significantly different prognoses." Now, these are separated into Grade Groups 4 and 5.

Here is the Breakdown for the New Grade Group System:

• Grade Group 1 (Gleason score 3+3=6)
• Grade Group 2 (Gleason score 3+4=7)
• Grade Group 3 (Gleason score 4+3=7)
• Grade Group 4 (Gleason score 8)
• Grade Group 5 (Gleason scores 9-10)

Will this new system be coming soon to a hospital near you? Yes. It has been accepted by the World Health Organization, and will be used in conjunction with the current system "until it becomes widely accepted and practiced," says Epstein.