Monday, July 11, 2011

Understanding The Gleason Score And Its Implications

For men in the prostate cancer community, a Gleason Score is sort of like an identity badge.  This simple number, used to grade the severity of prostate cancer, is forever etched into the minds of men diagnosed with prostate cancer.  Knowing this number is crucial in determining how to approach the prostate cancer and whether the cancer even needs to be addressed.  The simple number obtained from a prostate biopsy can also speak volumes as to what kind of prognosis a man with prostate cancer can expect.  In this post, I will explain how a Gleason Score is determined, explain its significance, and provide a very important warning about the dangers of relying on this number too greatly.

What is a Gleason Score?

About 40 years ago a pathologist in Minnesota named Donald Gleason evaluated the pathology specimens of hundreds of veterans diagnosed with prostate cancer.  He attempted to correlate how prostate cancer looked under the microscope with how men faired clinically.  In essence, he tried to look for patterns of the prostate cancer cells that could be then linked to prognosis and outcomes.  In so doing, Doctor Gleason created the grading system currently used worldwide to microscopically evaluate prostate cancer.

The Gleason score is determined by first surveying prostate samples under the microscope.  When prostate cancer is identified, it is evaluated in terms of how aggressive it looks.  Specifically, the pathologist looks at the shape and size of the cells, how they stick together, and whether they take the form of glands or simply look like amorphous sheets.  This last characteristic is called differentiation.  Well differentiated tumors look more like normal glands while poorly differentiated tumors do not really look like anything more than random cells stuck together.  Depending on this microscopic appearance, pathologists score the cancer on a scale of 1-5, with 1 being very mild or well differentiated and 5 being extremely aggressive or poorly differentiated.  After grading all of the cancerous areas in this fashion, the pathologist next determines the two types of tumors he sees most frequently in the specimen.  He then adds these two numbers up to get the Gleason Score.  For example, if the pathologist finds that 60% of the cancer is Grade 3 and 40% is Grade 4, the Gleason Score would be 3+4=7.  In short, the cancer in this example would be labeled Gleason 7. The Gleason Score can range from a score of 2(1+1) through 10 (5+5).  In reality, however, individual Gleason Scores of 1 or 2 are no longer seen as most pathologists no longer consider these patterns as true cancer.  Instead, practically speaking, the lowest individual score is 3, making the lowest realistic Gleason Score 6.  Rarely, a total Gleason Score of 5 may still be encountered.

Why is the Gleason Score Significant?

Gleason scores, themselves, are also grouped into categories.  Gleason 6 disease is considered mild to moderate risk prostate cancer.  It is the run-of –the-mill prostate cancer that most men get.  Gleason 6 cancer is the type to think about when you hear that prostate cancer is slow growing and MAY not affect you.  In contrast Gleason 8-10 cancer is considered aggressive cancer that most likely will affect you, particularly if you do nothing about it.  Prostate cancer with a Gleason Score of 8-10 is much more likely to grow outside of the prostate, leave positive margins after prostatectomy, and metastasize to the bones or lymph nodes as compared with cancer of a lower Gleason grade.  In addition, a Gleason Score of 8-10 significantly impacts the survival of men with prostate cancer.  A classic study followed men with prostate cancer that were treated conservatively.  After 15 years, the study reported that men in their 50s diagnosed with a Gleason 8-10 prostate cancer had an 80% chance of dying from the cancer as opposed to 20% for men with Gleason 6 disease.  I should, again, stress that these statistics were for men NOT aggressively treating their cancer, which truly demonstrates that differing natural history of Gleason 6 versus Gleason 8-10 disease.

In between Gleason 6 and Gleason 8-10 disease, of course, lies Gleason 7.  This type of prostate cancer is moderately aggressive with a prognosis that logically falls between the two groups.  In the above mentioned study, for instance, about 60% of men in their 50s died of Gleason 7 prostate cancer after 15 years.  Gleason 7 disease, however, can be more of a wild card.  It is very hard to predict how aggressive such disease really is.  Some Gleason 7 cancers behave more like Gleason 6 disease while others act much more aggressively, like Gleason 8-10 tumors.  Some of this discrepancy may have to do with whether a Gleason 7 cancer is 4+3 or 3+4.  As you may recall, the Gleason score is a sum of the two most commonly found cancer patterns in a prostate specimen.  In a Gleason 4+3=7 tumor, the more aggressive type 4 pattern is found in greater abundance than the milder type 3 pattern.  The opposite is true for Gleason 3+4=7 disease.  Studies have demonstrated that Gleason 4+3=7 disease is much more aggressive than Gleason 3+4=7 tumors.  One study, for example, demonstrated that after 5 years of follow up, men treated for Gleason 4+3=7 prostate cancer demonstrated a 40% risk of cancer progression as opposed to a 15% risk for their counterparts treated for Gleason 3+4=7 disease.  Hence, this small distinction may make a significant difference in treatment planning and prognosis and may explain why not all Gleason 7 tumors are the same.

The Pitfalls of the Gleason Score

Because the Gleason Score has demonstrated such correlations with outcomes for men treated for prostate cancer, it is heavily relied upon in making treatment decisions.  For those men choosing active surveillance rather than treatment, for example, a Gleason Score less than 7 is really mandatory.  As such, the Gleason Score can have a monumental impact on future quality of life.  The problem with relying on the Gleason Score from a prostate biopsy, however, is that this score is not always accurate.  Because the score is subjectively determined by a pathologist, there can be a great deal of variability in scoring.  One study, for example, reported that when prostate biopsy specimens were sent for a second opinion, 7% of tumors initially graded Gleason 6 were upgraded to a Gleason 7 while 16% of tumors initially graded Gleason 7 were downgraded to Gleason 6.  As I described above, this one point disparity can have a significant impact on treatment decisions and outcomes.  This is particularly true for men who choose active surveillance for what they think is Gleason 6 disease but , really, have Gleason 7 prostate cancer. 

Another limitation of a Gleason Score determined from a prostate biopsy is that a biopsy may not provide a representative sample of the entire prostate.  Each biopsy sample is only a few centimeters long and a few millimeters wide as compared to the entire prostate, which can range in size from a walnut to a peach.  As a result, the Gleason Score on prostate biopsy is usually accurate only about 50% of the time as compared to the Gleason Score determined when the whole prostate is subsequently removed and examined after a prostatectomy.  One study, for example, evaluated 134 men with Gleason 6 prostate cancer on biopsy who subsequently underwent prostatectomy.  The study reported, that 50% of these men (who were thought to have Gleason 6 cancer) were actually determined to have Gleason 7 prostate cancer when the entire prostate was evaluated after prostatectomy.

Fortunately, studies have provided some guidance as to how to better determine if  a biopsy Gleason score may be underestimating the true aggressiveness of a given prostate cancer.  These studies have demonstrated that other aspects of the prostate cancer, gleaned from the biopsy and clinical information, may help predict more aggressive disease.  For example, men with a PSA greater than 5 and a prostate less than 60 grams in size may actually have more aggressive disease than the Gleason 6 prostate cancer found on biopsy.  In addition, prostate cancer that occupies more than 5% of the total biopsy tissue, is found on more than 1 biopsy core (sample), or takes up more than 10% of any core is likely to be more aggressive than the biopsy Gleason Score is reporting.  As a result, many active surveillance protocols exclude men with the criteria above despite the fact that they have only Gleason 6 disease.

Take Home Message

The Gleason Score is a very important characteristic of prostate cancer.  It is like a cancer ID card that allows urologists to determine prognosis and guide treatment decisions based on the appearance of prostate cancer cells under the microscope.  While a useful tool in evaluating prostate cancer, however, the Gleason Score can prove to be a double edged sword.  Gleason Scores reported on prostate biopsies are often inaccurate due to pathologist error or as a result of poor sampling.  As a result, the Gleason Score reported on a prostate biopsy can underestimate the true aggressiveness of prostate cancer.  While this inaccuracy may not be important for a man choosing to proceed with a prostatectomy or with radiation therapy, it can be critical for those men choosing to forego treatment and, instead, proceed with active surveillance.  For those men, it may be beneficial to get a second pathological opinion to make sure that their Gleason 6 prostate cancer is actually Gleason 6.  In such situations, looking at the Gleason score in the context of other risk factors such as PSA and tumor volume may also help determine the accuracy of the biopsy Gleason Score and provide some added reassurance that a more aggressive cancer is not lurking undetected in the prostate.  As always, talk to your urologist and make sure that you are getting all of the information necessary to make a knowledgeable decision about your prostate cancer.

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  1. A very nice summary, however you may want to consider discussion section for when tertiary gleason 5 is noted.

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  2. Doc - any thoughts on using more than 12 core bx -- even for initial biopsy -- to increase the odds of an accurate diagnosis? Maybe a mapping biopsy? Seems those are reserved for subsequent bx, but I am not sure why. Also, what do you think about use of MRI or color doppler ultrasound in an effort to target biopsies?

  3. Bill Manning: Thanks for the feedback. Tertiary Gleason 5 is a pathologic characteristic usually found in the final pathology rather than the biopsy pathology. In biopsies a tertiary score of 5 gets incorporated into the actual Gleason score. For example, if a prostate biopsy shows mostly Gleason 4 and 3 cancer but has 5% Gleason 5, the usual custom is to clasify it as 4+5 rather than 4+3 because of the significant change in prognosis that the Tertiary 5 produces. In prostatectomy specimens, in contrast, pathologists would report this example is Gleason 4+3 with tertiary Gleason 5. This would similarly impact the prognosis negatively. However, the Gleason score of 7 is maintained in the prostatectomy example. Hope that helps. I did not want to include this in the original post as I thought it would be confusing for readers.

  4. Chamorgadol: Most studies have not demonstrated significant advantages of saturation biopsies greater than 12 cores, particularly for an initial biopsy. Remember also, the goal is to find SIGNIFICANT cancer, which can usually be identified on a 12 core biopsy. As for MRI and color doppler ultrasound, some encouraging results have been reported in helping identify elusive cancers but widespread use for all biopsies would be cost prohibitive.