Tweaking the Gleason System:
Is there a Better Way to Grade Prostate Cancer?                                

The Gleason grading system for prostate cancer is at once helpful and confusing for doctors and patients. Part of the confusion is that the Gleason number represents a combination of cell patterns that the pathologist sees in biopsied prostate tissue samples under the microscope. The most common cell pattern and the second-most common pattern are added together, and the sum is the Gleason score. "There are some problems with the Gleason system," says pathologist Jonathan Epstein, M.D., the Rose-Lee and Keith Reinhard Professor in Urologic Pathology. Briefly, the Gleason system assigns scores to prostate cancer cells based on how they look, on a scale from 2 to 10. The most normal-looking, slowest-growing cells have the lowest numbers; at the high end of the scale are very malignant cells that are more aggressive and spread quickly. But no man ever gets a score of Gleason 2.

"Patients will be reassured that
when they’re diagnosed with a
Gleason score 6, this means that
their Prognostic Grade Group is I
out of V, not six out of 10."

"Gleason score 6 is typically the lowest grade assigned," says Epstein, and "patients are unduly concerned when they’re told that they have Gleason score 6 cancer, logically but incorrectly assuming that their tumor is in the mid-range of aggressiveness." Gleason score 7 disease can have two meanings: If the most common cell type is Gleason 3, with fewer Gleason 4 cells, this is considered "Gleason score 3+4=7" disease. "In the past, any Gleason pattern 4 tumor was considered aggressive," says Epstein. "But we showed that Gleason score 3+4=7 cancer has a very favorable prognosis, with over 90 percent of men cured after radical prostatectomy." On the other hand, if there are more Gleason 4 and fewer Gleason 3 cells, this is "Gleason score 4+3=7" disease, and it is significantly more aggressive. Gleason scores 8-10 tumors are routinely grouped together, Epstein continues, "but we found that although Gleason score 8 tumors are aggressive, they are not as aggressive as Gleason score 9-10 cancers."

In an article recently published in the British Journal of Urology, Epstein and colleagues Phillip M. Pierorazio, Patrick Walsh, and Alan Partin suggested grouping Gleason scores into five prognostic groups, as opposed to the individual nine Gleason scores. "Patients will be reassured," says Epstein, "that when they’re diagnosed with a Gleason score 6, this means that their Prognostic Grade Group is I out of V, not six out of 10." Similarly, men with Gleason score 3+4=7 cancer would be placed in Prognostic Grade Group II, "which is in line with their tumor’s relatively less aggressive behavior. At the other end of the grade spectrum, men with Gleason score 9-10 tumors will be more accurately considered to have more aggressive tumors than those with Gleason score 8, and this can be factored into their treatment decisions."

Good News for Men with Gleason Score 6

In other news, Epstein and colleagues recently took a closer look at the behavior of Gleason score 6 prostate cancer; their findings were published in the American Journal of Surgical Pathology. Although Gleason score 6 cancer is considered slow-growing and not aggressive, it has been found – rarely – in studies of prostate specimens after radical prostatectomy, to have spread outside the prostate. Could Gleason 6 cancer ever spread to the pelvic lymph nodes? Good news: The answer is no. "We performed a search of the radical prostatectomy databases at four large academic centers," says Epstein. "In more than 14,000 radical prostatectomies, there was not a single case of a Gleason score 6 tumor ever spreading to lymph nodes." It takes a Gleason score of 7 or higher for prostate cancer to become aggressive enough to spread far beyond the prostate. Under the microscope, Gleason score 6 cells appear uniform, "and they have a more predictable, excellent prognosis," Epstein notes. Gleason score 6 disease has such a good reputation as being "indolent" – slow-growing and wellbehaved, as cancers go – among pathologists that some of them have questioned whether it should still be considered cancer. Yes it should, Epstein says. One important reason why is that the biopsy Gleason score is often adjusted after radical prostatectomy, when the prostate is studied by a pathologist, "because the biopsy often underestimates disease grade and extent." Also, "if men think that Gleason 6 tumors are not cancer, this could result in a missed opportunity for cure."

A New Approach

Five Gleason Groups Based on Prognosis

Prognostic Group I:
Gleason score <6,

Prognostic Group II:
Gleason score 3+4=7

Prognostic Group III:
Gleason score 4+3=7

Prognostic Group IV:
Gleason score 8

Prognostic Group V:
Gleason score 9-10


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