Dr. Jonathan Epstein, of The Urologic Pathology Laboratory at Johns Hopkins Hospital, is a leading authority in urological pathology of prostatic and bladder disease. He is the author of over 800 articles, as well as the definitive texts, Prostate Biopsy Interpretation and Bladder Biopsy Interpretation. Dr. Epstein consults frequently with pathologists, physicians, and patients.
Prostatepedia spoke with him recently about a new grading system he developed to replace the current Gleason score.
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Can you describe the Gleason grading system for prostate cancer?
Dr. Epstein: The original Gleason system was developed from 1967 to 1973. It stayed the same until 2005. The Gleason system says that often tumors have more than one pattern and asks what is the most common pattern. A tumor ranges from pattern 1, which is the lowest (most favorable) to 5, which is the highest (most aggressive). The tumor may be 70% pattern 3. We then ask, “What is the second most common pattern?” The tumor may be 30% pattern 4. We add those two patterns together: 3 + 4 = 7.
A tumor theoretically could be pure 1. We call that a 1 + 1 = 2. That is the lowest Gleason score you can get. For a tumor that is very bad—all undifferentiated, aggressive tumor that is pure pattern 5—we call it a 5 + 5 = 10. There are 25 different combinations of 1 + 2 = 3, 4 + 4 =8, 4 + 5 = 9, etc. That is the Gleason system: looking at architectural patterns, giving them different patterns from 1 to 5 and adding the most common and the second most common together.
Of course, the field of prostate cancer has changed from Gleason’s time to now. We have PSA screening. We have modern tests to diagnose lesions.
In 2005, I led a consensus conference to update the Gleason system. We changed some of the terms of various Gleason patterns. We stopped calling very low-grade patterns cancer. Theoretically, you could have a 1 + 2 = 3 or a 2 + 2 = 4. However, in general, even though the Gleason grade goes from 2 to 10, in practice, prostate specimens start at 6. This is obviously very confusing to patients.
There was an impetus to have a conference to update the Gleason system once more in 2014 because of active surveillance. Back in 2005, active surveillance wasn’t invoked that much. In general, if you had cancer, you were treated. But today, 40 to 50% of men diagnosed with relatively indolent prostate cancer in the United States opt for active surveillance.
The question became: can we grade prostate cancer in such a way that we can help identify which patients are best suited for active surveillance?
What do you see as the deficiencies of the current Gleason grading system?
Dr. Epstein: The main deficiency of the Gleason grading system is that while the grades range from 2 to 10, 6 is the lowest. What other system in any cancer starts with 6 as the lowest grade? It doesn’t intuitively make sense.
The other problem is we have this Gleason 7, which could either be mostly pattern 3 with a little bit of 4 (3 + 4 = 7) or mostly pattern 4 with a little bit of 3, which is a 4 + 3 = 7. Both of these cancers would be a 7. It’s confusing, because they sound like they could be the same, but in fact patients with a 3 + 4 = 7 have an 88% cure rate with surgery, while those with a 4 + 3 have only a 65% cure rate with surgery.
Some men with a limited 3 + 4 might be able to undergo active surveillance, but that is still in question. No one with a 4 + 3 would undergo active surveillance. Gleason 7 is confusing.
It’s also confusing that clinicians lump whatever Gleason scores they want together into one group. Clinicians often lump Gleason 8, 9, and 10 together, but in fact, Gleason 8, while aggressive, has a much better prognosis then a Gleason 9 or a 10. The current system causes fear for patients.