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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.

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.

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.

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.

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.

One of the biggest concerns on the minds of my patients is whether they actually need to get treated for prostate cancer.  Numerous studies have been mentioned in the media that demonstrate a significant overtreatment of prostate cancer.  One large study concluded that as many as 50 men might have to undergo treatment for prostate cancer to prevent one death from the disease.  These studies, although large, did have significant limitations.   As a result, we have to take these findings with a grain of salt.  Nonetheless, statistics like this do need to be taken very seriously.  Imagine if I told you that there is only a 1 in 50 chance that you actually NEED the treatment for prostate cancer that you are scheduled to receive.  Would you still be willing to take on the significant risks of these treatments?  However, when we talk about studies like this, we tend to paint everyone with the same brush.  Not all prostate cancers behave the same way.  While some move extremely slowly others can grow and spread in a short period of time.  As a result, while prostate cancer is, indeed, probably over treated today, ignoring it altogether can also lead to catastrophic results.  In this post, I will attempt to differentiate the types of prostate cancer that can and CANNOT be followed. I will also explain active surveillance, the protocol used to follow patients with a “watchful waiting” approach.  Finally, I will describe the results of studies evaluating the results of such active surveillance protocols for appropriately selected patients.

The types of prostate cancers that are most likely over treated today are called “low risk” prostate cancers.  What makes these prostate cancers low risk?  There are actually very specific criteria:

1)      Low risk prostate cancer tends not to have a Gleason score greater than 6, making it a low to moderate grade cancer.  This grade is determined by a pathologist from a prostate biopsy depending on how the prostate cancer cells look under the microscope.  Gleason 6 prostate cancer is what I call “run of the mill” prostate cancer. It is the type that is seen most commonly in practice and is very successfully treated. 

2)      Another criteria has to do with how much cancer is found in the biopsy specimen.  Prostate cancer that is found in less than 30% of the specimens obtained and taking up no more than 50% of each specimen is considered low risk.  For example, if your urologist took 12 biopsy samples, no more than 4 samples should demonstrate cancer and no more than ½ of each sample should be taken up by cancer for your prostate cancer to be considered low risk. 

3)      Your PSA also impacts the risk of prostate cancer.  Low risk prostate cancer is associated with a PSA less than 10.  Because PSA can also be high due to large prostate size, PSA density is also used to assess risk.  PSA density is your PSA divided by the volume of your prostate (this is determined during the prostate biopsy with the ultrasound machine).  For example if your PSA is 10 and your prostate volume is 40, your PSA density is 0.25.  Studies have demonstrated that a low risk PSA density is less than 0.15.

4)      The way your prostate cancer was discovered also helps to determine the risk level.  Prostate cancers detected through an elevated PSA(stage T1c) or through a small nodule found on one side of the prostate during rectal exam(T2A) are considered low risk.

Prostate cancers that meet ALL of the above criteria are the ones that are considered to be over treated.  Studies have demonstrated that men with these low risk cancers can have their cancers monitored rather than treated without significant risk.  I will explain the results of these studies later in the post.  First, I want to describe active surveillance, the actual protocol that should be used to follow patients with low risk prostate cancer.

When you and your doctor decide not to treat prostate cancer, you are not deciding to ignore it altogether.  Based on what they read on the internet, many of my patients come to me with the idea that once you forgo treatment, the prostate cancer becomes just a bad memory that you just need to put out of your mind.  In reality, nothing could be further from the truth.  Of course, there are those patients who completely ignore their prostate cancer diagnoses for years.  Unfortunately, those are the same patients that I often see some years after their initial diagnoses with painful widespread metastases and no hope of cure. 

For those men that follow a true active surveillance protocol, “active” is the critical term.  When I place a patient on an active surveillance protocol we agree to a pretty rigorous follow up regimen.  I see him back every 6 months and perform a rectal exam and a PSA test.  If the PSA goes up or the exam reveals a new, suspicious finding, we proceed with a repeat prostate biopsy.  Otherwise, if there is no change in either, we agree to repeat a prostate biopsy in 12-18 months.  After this repeat biopsy, we reassess the situation.  We see if the cancer has changed and is no longer in the low risk category.  If the cancer does not conform to all of the above criteria it cannot be considered low risk any longer.  In that situation, we again go over treatment options and, usually, the patient chooses one and proceeds with treatment.  If, on the other hand, the prostate biopsy still demonstrates low risk disease, most patients continue on the same active surveillance regimen.  The only difference with the regimen at this point is that the next prostate biopsy is usually stretched out to 18-24 months in the future.  Some patients actually switch to treatment despite the persistence of low risk disease for various reasons.  As you can see, in reality, active surveillance is a lot more involved than just looking the other way.

The above mentioned protocol for active surveillance did not just appear as a whim of some urologist who wanted to see his patients more often.  The regimen was actually born out of numerous studies evaluating how patients with prostate cancer did on various protocols.  Most studies to date have demonstrated that active surveillance protocols like the one mentioned above are very safe.  These studies have demonstrated that only about 25-40% switch from surveillance to treatment over a 10 year period.  That is a substantial finding as more than 50% of these patients could hold off on treatment for a decade and still feel relatively safe about their prostate cancer.  This feeling of safety comes from the fact that nearly all of the studies demonstrated that only a tiny minority of patients fall through the cracks and actually develop advanced, metastatic disease if they adhere to the protocol.  In fact, a recent study actually revealed that 5 patients died of prostate cancer out of 1800 followed with an active surveillance protocol.   Again, I cant mention enough that these studies were performed on patients with LOW RISK PROSTATE CANCER .  Protocols for patients with slightly higher risk disease are emerging but, in my opinion, are not quite ready for mainstream use…at least not if you want to sleep at night. 

If you don’t take home anything else from this post, I hope that you understand that the decision of whether or not to treat prostate cancer is complicated.  It is absolutely true that not ALL people need to be treated for prostate cancer.  At the same, time, however, it is also absolutely NOT true that prostate cancer is just an innocent victim with a bad reputation and that NO man with prostate cancer needs treatment.  The decision to forgo treatment and proceed with an active surveillance protocol depends on numerous factors:

As we learn more and more about prostate cancer, we are beginning to see that not all prostate cancers need to be treated, at least not right away.  The decision to not treat prostate cancer can be a very good and safe one for SELECT patients in SPECIFIC situations.  However, such a path should not and cannot be generalized and applied to ALL men with prostate cancer.  As always, make sure you obtain all the important details about your prostate cancer diagnosis and discuss the options thoroughly with your doctor. The more knowledge you have, the better decisions you will make.