Thursday, November 17, 2011

Androgen Deprivation Therapy For Prostate Cancer: Understanding How It Works

Approximately one third of men with prostate cancer will eventually need androgen deprivation therapy.  While this treatment was first used for advanced, metastatic prostate cancer, androgen deprivation therapy is increasingly used for other indications as well.  Many patients undergoing radiation therapy for aggressive prostate cancer are treated concurrently with androgen deprivation therapy to maximize treatment outcomes.  Men with PSA recurrence after prostatectomy are also placed on this therapy.  Despite the frequency with which androgen deprivation therapy is used, many men undergoing the treatment don’t know how it works. In this post, I will introduce androgen deprivation therapy.  Specifically, I will focus on the first line androgen deprivation therapy and how it works.

The Food of Prostate Cancer

One of the most important discoveries related to prostate cancer was that androgens serve as the fuel or food of prostate cells and prostate cancer cells.  Androgens are basically male hormones.  They are the compounds, circulating in the bloodstream, which give men their masculine features.  The most famous androgen, testosterone, is mainly produced in the testes.  Other, less potent androgens are also produced in the adrenal glands.  Once produced, testosterone and the adrenal androgens are secreted into the bloodstream and travel to the prostate.

Testosterone binds to a target on prostate cells called the androgen receptor.  By binding the androgen receptor, testosterone initiates a cascade of events that stimulates further growth and multiplication of the prostate cells.  The same occurs with prostate cancer cells which, fueled by testosterone, multiply and spread to distant sites in the body. 

Starving the Beast

The understanding that prostate cancer feeds on testosterone was perhaps the fundamental discovery in the battle against the disease.  With this understanding, the next obvious step was to try to prevent prostate cancer cells from obtaining their fuel.  The most direct way of ridding the body of testosterone is to get rid of the source: the testicles.  As a result, the first form of androgen deprivation therapy was simple surgical castration.  By surgically removing the testicles, doctors were able to dramatically and rapidly decrease the level of circulating testosterone and, in turn, significantly slow down the growth of advanced prostate cancer.  Of course, surgical castration has its downsides.  Most men are psychologically impacted by having their testicles removed and would rather avoid surgery.  As a result, the search began for a chemical means to decrease the amount of testosterone in the body.

Chemical Castration

A turning point in the treatment of prostate cancer came with the discovery that the  production of testosterone in the testicles is not constant or automatic  Rather, it is regulated.  Studies demonstrated that the presence of testosterone or estrogen (the female equivalent of testosterone) in the bloodstream have a negative effect on the production of testosterone by the testicles.  In other words, the body regulates the amount of sex hormones in the blood stream by a process of negative feedback: large amounts of circulating sex hormones actually inhibit the testicles from producing more testosterone.  Negative feedback is a useful regulatory tool that the body uses to make sure that too much of given compound is not produced or present at a given time.

The discovery of negative feedback led to the use of an estrogen-like compound called DES in treating advanced prostate cancer.  Scientists reasoned that the presence of this ingested estrogen analog in the bloodstream could provide the negative feedback to the testicles needed to stop testosterone production.  As a result, they reasoned, prostate cancer would be starved of its vital fuel.  Turns out, they were right.  The use of DES worked incredibly well in reducing the growth and extent of prostate cancer.  However, it was soon discovered that men treated with DES suffered from heart attacks and other blood clots.  As a result, DES was no longer offered for men with advanced prostate cancer.

The real breakthrough in androgen deprivation therapy came in the late 1970s when the actual mechanism behind the negative feedback regulation of  testosterone production was revealed.  At that time, it was demonstrated that the negative feedback which regulates testosterone production by the testicles is actually carried out by hormones produced in the brain.  A part of the brain called the hypothalamus produces a compound called gonadotropin releasing hormone(GNRH) which stimulates another part of the brain called the pituitary gland to produce a hormone called leutinizing hormone(LH).  LH travels from the brain through the blood stream and into the testicles to stimulate the production of testosterone. High levels of testosterone and/or estrogen circulate through the bloodstream to the brain to provide the negative feedback.  This negative feedback allowed DES (a compound very similar to estrogen) to successfully decrease testosterone production and limit the growth of prostate cancer.

Stemming from this discovery was the further understanding that the hypothalamus usually emits GNRH in spurts rather than in a continuous fashion.  As long as this hormone is released in this fashion, the pituitary gland will continue to produce LH.  In turn, the LH will then stimulate testosterone production by the testicles.  However, researchers found that if the GNRH is secreted continuously it would actually decrease LHRH by the pituitary which would then decrease the production of testosterone by the testicles.  With this discovery, modern androgen deprivation was born in the form of GNRH agonists like Leuprolide and Goserilin.  These monumental drugs, used in mainstream androgen deprivation protocols today, work by maintaining a steady, continuous flow of GNRH which serves to shut down production of LH by the pituitary and, subsequently, stops the production of testosterone by the testicles.

Several years later, this discovery of the pathway and regulation mechanisms of testosterone production led to the development of another class of drugs used in androgen deprivation.  Rather than relying on GNRH analogs that shut down the production of LHRH in the pituitary, researchers developed a compound that inactivates GNRH altogether.  These GNRH antagonists, like Abarelix and Degarelix, have some important advantages over GNRH agonist drugs.  However, due to cost issues and some important side effects, these drugs have not reached the same level of mainstream use as GNRH agonists except for certain specific indications.  I will further explore this issue in a future post.

Take Home Message

Modern androgen deprivation therapy has evolved greatly over time.  From surgical castration to GNRH agonists and antagonists, the treatment of advanced prostate cancer has become more and more refined as discoveries have shed greater light on how the food of prostate cancer is created and regulated.  Understanding this background can help men undergoing androgen deprivation therapy have a better grasp of the rationale behind the often complex twists and turns experienced during their battle against advanced prostate cancer.  In future posts, I will build upon this background to explain some limitations and pitfalls of androgen deprivation therapy as well as to describe what happens when such first-line therapy fails.

This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

Sunday, September 18, 2011

Choosing The Right Treatment For Localized Prostate Cancer: Consider Quality of Life

“Which is the best treatment?”  That is one of the most common questions that I hear from men during counseling for localized prostate cancer.  My patients carefully listen to the risks and benefits of the various treatment options including radical prostatectomy, external beam radiation therapy, and brachytherapy.  They then always turn to me to see which is the best treatment for them.  For men with moderately aggressive, localized prostate cancer, there is no right answer.  Studies have shown that for most men with a PSA less than 10 and Gleason 6 prostate cancer that is not palpable (or minimally palpable) on rectal exam, no single treatment option has been definitively demonstrated to cure prostate cancer better than the others.  This information usually confuses many of my patients.  After all, how can you choose between therapies when they all treat the cancer about the same? 

The answer is side effects

While the ability to cure cancer is fairly similar for the three mainstream treatment options, their side effect profiles tend to be very different.  As I tell my patients, there is no free lunch in medicine.  Any treatment you choose will result in some unpleasant outcomes.  The key is determining which side effects you think you will best be able to tolerate.  The treatment that you think will least impact your quality of life is probably going to be the best treatment option for you.  In this post, I will review the different ways that radical prostatectomy, external beam radiation therapy, and brachytherapy affect quality of life.

Breaking Down Quality of Life

Treating prostate cancer can affect a man’s quality of life in many different ways.  Urination, bowel function, and sexual performance can each be impacted by the various treatment options.  Studies often evaluate these categories or “domains” separately to help determine a man’s quality of life after treatment for prostate cancer.  Lets try to look at these categories individually.


As I have described in my previous posts, most treatments for prostate cancer affect urination.  During a prostatectomy, one of the two muscles responsible for controlling the flow of urine is removed with the prostate. As a result, the work is left to the remaining muscle.  This muscle is often not strong enough to control urination, at least not initially.  As a result, most men leak after prostatectomy.  Not surprisingly, studies have demonstrated that urinary function (a quality of life term for continence) is significantly worse for men undergoing surgery as compared with those men undergoing radiation therapy.

In contrast, radiation treatments such as external beam therapy or brachytherapy do not involve the removal of any muscles.  Because the “plumbing” remains intact, men undergoing these treatments usually do not experience any incontinence of urine.  However, radiation therapy does cause other problems with urination.  The radiation often causes swelling of the prostate, which makes it harder for the urine to travel through it from the bladder.  To better understand this concept, picture the bladder as an upside down fishbowl which empties through a donut (the prostate) into a straw (the urethra) and out the penis.  Radiation therapy causes swelling of the donut (the prostate), making the donut hole smaller and slowing the flow of urine.  While most men are not too bothered by this, those men that already have enlarged prostates and BPH (benign prostatic hypertrophy) symptoms often complain that their symptoms become worse with radiation.  In a minority of men, the swelling induced by radiation can be so great as to completely obstruct the flow of urine and require the placement of a catheter in the bladder.  Men with significant BPH should give definite consideration to these possibilities before proceeding with radiation therapy.

In addition to impacting the prostate, radiation therapy given for prostate cancer can also affect the nearby bladder.  Although modern radiation technology is getting more and more precise in aiming radiation beams at the prostate, the bladder does invariably absorb some of the radiation.  As a result, the bladder can become irritated or inflamed from the beams.   Men experiencing such irritation of the bladder often complain of pain with urination and find themselves urinating more frequently, but in smaller quantities.  Rarely, blood in the urine can also be seen due to the irritation of the bladder from the radiation beams.  Of note, these symptoms of urinary irritation and obstruction are experienced more often by men undergoing brachytherapy than by those men treated with external beam therapy.

Bowel Function

Anyone who has ever undergone a prostate biopsy knows just how close the prostate is to the rectum.  As a result, treatment for prostate cancer can affect bowel function and quality of life from a digestive standpoint.  Fortunately, barring rectal injury (which occurs less than 1% of the time), a radical prostatectomy should not lead to any significant problems with bowel function.  As a result, men undergoing prostatectomy usually express no long term detriment to quality of life from the standpoint of their digestive tract.  The same cannot be said, however, for those men undergoing radiation therapy.  Because the rectum is located just behind the prostate, radiation beams directed at the prostate can also hit the rectum and lead to side effects.  Common complaints can include some transient (or, rarely, long term) diarrhea, pain with bowel movements, or blood in the stool.  Fortunately, with improvements in radiation technology, the incidence and extent of bowel problems is seen less and less.  Nonetheless, these therapies cause significantly more bother due to gastrointestinal side effects than does radical prostatectomy.  When comparing the two types of radiation therapy, studies have demonstrated that external beam therapy tends to cause more bowel problems than brachytherapy. 

Sexual Function

Because of the proximity of the nerves controlling erections to the prostate, all treatments for prostate cancer affect sexual function.  Because the nerves can be damaged during a prostatectomy, erectile dysfunction is usually noted immediately after surgery.  In some men, these nerves recover over time and some function is regained months to years after surgery.  Nonetheless, at least half of the men undergoing prostatectomy do complain of some decrease in sexual function over the long term. 

Radiation therapy, as well, can damage the nerves responsible for erections.  Because the damage inflicted by radiation therapy occurs over time, however, the impact on sexual function is not usually experienced at the time of or immediately after treatment.  Rather, erectile dysfunction after radiation therapy usually takes weeks to months to take hold.  Nonetheless, studies have demonstrated that a similar percentage of men (50%) experience some long term decrease in erectile function after radiation therapy.  As such, studies have not demonstrated any significant differences in sexually related quality of life between external beam radiation and radical prostatectomy.  In contrast, some studies have demonstrated better sexual function after brachytherapy as compared to surgery or external beam therapy.

Aside from erectile function, another aspect of sexual quality of life that must be kept in mind is ejaculation.  During a prostatectomy, the prostate and seminal vesicles are removed and the vasa deferentia are tied off.  This effectively removes all potential fluid that is released during ejaculation.  As such, while men can experience orgasms after prostatectomy, these orgasms feel different in that they are associated with a dry ejaculate.  In my practice, many men have complained that the lack of ejaculated semen leads to decreased enjoyment from orgasm and from the sexual experience in general. While this is not a commonly discussed side effect of prostatectomy, it can significantly affect sexual quality of life and should be kept in mind by men considering prostatectomy.

Take Home Message

The abundance of treatment options available to men with prostate cancer can be a blessing and a curse.  On one hand, it is always good to have options when battling a disease.  On the other hand, however, it is difficult to choose between treatment options when you know that, at least in terms of cancer cures, the options yield very similar results.  As such, in treating prostate cancer, the decision often comes down to side effects rather than cure rates.  As I tell my patients, there is no free lunch in medicine.  Any treatment has its own set of risks and side effects.  However, for every individual, some risks are more daunting than others.  While some men are deathly afraid of incontinence others are more concerned about erections.  Still others would trade both for normal bowel habits.  As such, the decision on how to proceed with treatment of prostate cancer is usually a very personal one.  While the urologist can make recommendations in specific cases when one treatment may be more medically advantageous, the patient is best suited to make the final treatment decision, in most cases, after a careful review of the options and an honest look within.

This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

Wednesday, August 17, 2011

Managing The Catheter After Prostatectomy Part II: After The Catheter Is Removed

In my last post, I explained the need for maintaining a catheter after a prostatectomy.  I also described what to expect with the catheter in place as well as red flags that may signal that something is wrong.  For men undergoing prostatectomy, the catheter can, indeed, be a daunting part of the journey.  Most men are quite relieved when the catheter is finally removed 1-2 weeks after the surgery.  Removing the catheter, however, is just another step in the recovery after prostatectomy.  After the catheter is removed, a whole new set of expectations and warning signals emerge that need to be understood by men after prostatectomy.  In this post, I will cover what to expect and look out for in the period immediately following the removal of the urinary catheter.

The Catheter Comes Out

For most men, the removal of the catheter is a very much anticipated milestone in the journey of recovery after prostatectomy.  The actual process of removing the catheter is not a huge undertaking, although it may appear a little daunting.  As I explained in my last post, the catheter is maintained in place by means of a balloon inflated within the bladder.  In order to remove the catheter, the doctor or nurse will attach a syringe to a port on the catheter and suck out the fluid from the balloon.  Once the balloon is deflated, the doctor can simply slide the catheter out from the penis.  Most patients describe the feeling of the catheter coming out as a “pop” that lasts for 1-2 seconds and then is associated with a feeling of relief.  In some men, the sensation can be more painful and last a little longer.

Some doctors will fill the bladder with fluid through the catheter prior to removing it.  The doctor will infuse water or saline through the catheter until the patient feels full and needs to urinate.  At that point, the catheter is removed and the patient is allowed to urinate.  The reason for this extra step is to make sure that the patient is able to urinate after the catheter is removed.  Other doctors simply remove the catheter and have the patient return if they cannot urinate.  Either way, the process last 1-5 minutes and is usually much less traumatic than anticipated.

What to Expect Post Catheter

  1. Leakage:  As I explained in a previous post, most if not all men leak urine immediately after the catheter comes out.  This leakage is due to the fact that the muscle responsible for controlling urination, the sphincter, needs to strengthen after the surgery.  While some men leak only a few drops with heavy activity, others leak profusely without much exertion at all.  Regardless, most men will regain continence within the first year after surgery.  As I mentioned in a previous post, some actions can be taken to expedite the process and regain continence sooner:
  2. Frequent urination:  A prostatectomy is generally very traumatic for the bladder.  First, the plumbing below the bladder is rearranged.  In addition, during the surgery, the bladder is opened and repeatedly manipulated. Finally, the bladder is continuously irritated by the catheter for 1-2 weeks after surgery.  As a result, by the time the catheter is removed, the bladder is usually very irritated.  The same contractions of the bladder that occurred with the catheter in place often continue after it is removed.  These bladder spasms cause the frequent urge to urinate even when not much urine is present.  As a result, men sometimes complain that they are constantly running to the bathroom to urinate after the catheter is removed.  Fortunately, as the bladder adjusts to life without the catheter, this frequency and urgency of urination diminishes.
  3. Slight blood in the urine: While in the bladder, the urinary catheter often puts pressure on the bladder and urethra, holding back any minor bleeding from some small veins that may be opened or cut during the surgery.  Once the catheter is removed, these veins may ooze a little.  Also, some old blood trapped by the catheter may be released once the catheter is removed.  As a result, some men do complain of some blood in the urine after the removal of the catheter.  This usually makes the urine look pink or cranberry colored and resolves within a few days.
  4. Burning with urination: After a prostatectomy, the urethra and bladder are often “raw” from irritation from both the surgery and the catheter.  As a result, many men do complain of some burning each time they urinate.  This feeling usually goes away after a day or two.

Warning Signs After Catheter Removal

  1. Inability to urinate: A small minority of men are unable to urinate after the catheter is removed.  For most men, this problem is caused by swelling at the surgical connection between the bladder and urethra called the anastamosis.  This problem is usually solved by reinserting the catheter and keeping it in for another week or so to allow time for the swelling to subside.  Some doctors also give medicine to help speed up the process.  Either way, with a little time, the swelling usually goes away and the ability to urinate returns.  As I mentioned in my previous post, replacement of the catheter after a prostatectomy should only be performed by the urologist.  Improper placement can lead to a disruption of the anastamosis, an emergent return to the operation room, and a lifetime of incontinence.
  2. Significant blood in the urine:  While a small amount of blood in the urine is normal, urine that looks like pure blood is not.  This is especially true if large blood clots are also noted to pass in the bloody urine for a prolonged period of time.  This type of blood in the urine is a sign of ongoing bleeding that needs to be addressed.  Usually, it is due to bleeding from outside the prostate and bladder that is seeping in through the anastamosis.  Without a catheter in place, such bleeding can create a large blood clot (called a hematoma) in the pelvis and actually rip open the anastamosis, separating the bladder from the urethra.  Such a complication can be prevented through early recognition and management of the problem.  Again, such problems after prostatectomy should only be managed by the urologist and not by emergency room staff. 
  3. Air or debris in the urine:  Occasionally, after the catheter is removed, a patient may complain of passing some air through the penis when urinating.  While this can be normal for the first few times after catheter removal (because air was introduced into the bladder from the indwelling catheter), sustained air in the urine is definitely not normal.  Similarly, small bits of debris in the urine can be occasionally seen after the catheter is removed.  These bits are old blood clots.  However, continued passage of air and debris in the urine after catheter is a sign of a fistula between the urethra and the rectum.  A fistula is an artificial connection which allows contents from one organ to be passed to another.  In this case, an unrecognized injury to the rectum during a prostatectomy allows a hole in the rectum to attach itself to the anastamosis or a small hole in the urethra.  With time, this fistula grows and matures, allowing more and more air and stool to be passed into the urine from the rectum.  On occasion, urine is also allowed to pass into the rectum, causing diarrhea.  If this problem is not addressed in a timely fashion, the mixing of urine and stool can cause a serious and occasionally life threatening infection.

Take Home Message

The removal of the urinary catheter is an important milestone in the recovery from a radical prostatectomy.  The actual process of removing the catheter is usually very quick and straightforward, resulting in minimal discomfort.  Nonetheless, some common issues should be expected after removal, including leakage and some burning with urination.  In addition, patients having their catheters removed should know about red flags such as the inability to urinate as well as blood, air, or debris in the urine.  Reporting these issues to the urologist expediently can prevent significant problems from becoming dramatically worse.

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Tuesday, August 9, 2011

Managing The Catheter After Prostatectomy Part I: Expectations And Warning Signs

Men undergoing prostatectomy for prostate cancer face a recovery period that is somewhat different from other surgeries.  Unlike other surgeries, a radical prostatectomy requires a patient to wear a urinary catheter for 1-2 weeks after surgery.  This catheter is a narrow rubber hose that transports urine from the bladder, through the penis, and out to a bag outside of the body.  As you can imagine, this catheter takes some getting used to.  While most men do adjust well, others can have problems dealing with the catheter as well as complications associated with the device.  In this post, I will explain why a catheter is necessary after prostatectomy, what to expect when the catheter is in place, and common problems to look out for during this period.

Why is a Catheter Necessary?

In a previous post, I described the anatomy of the prostate and its relation to the bladder and urethra.  I think the best way to picture that layout is to imagine the bladder as an upside down fishbowl that pours urine through a donut (the prostate), and into a straw (the urethra within the penis).  During a prostatectomy, the prostate is removed and the bladder is directly connected to the urethra via stitches.  A catheter is passed through this connection (called the anastomosis) to allow it to heal without being disturbed by urine.  Generally, an anastomosis needs to keep dry to allow proper healing.  Otherwise, urine will leak through the anastomosis, creating a contracture (narrowing composed of scar tissue) which can impede the normal flow of urine out of the bladder. 

The amount of time the catheter spends in place depends on the type of prostatectomy performed.  For men undergoing open or traditional prostatectomy, the catheter time is usually 10-14 days.  In contrast, those men undergoing robotic prostatectomy usually only have to wear a catheter for 5-7 days.  This disparity has to do with the different ways the anastomosis is created in the two surgeries.  Robotic surgery tends to create an anastomosis that is usually more water tight and, so, heals a bit quicker.  As a result, the catheter does not need to stay in as long.

Common Complaints about the Catheter

1.      I feel like I am sitting on a ball:  One of the most frequent complaints I hear from men immediately after surgery is that they feel that they are sitting on a ball.  The reason for this feeling is often the part of the catheter located in the bladder.  The catheter is kept in place via an inflatable balloon which sits in the bladder.  After the catheter is placed, the balloon is inflated which prevents the catheter from sliding out the urethra.  This balloon is then deflated just prior to removal of the catheter.  Men often complain about feeling like they are sitting on a ball because they are actually sitting on one: the balloon of the catheter.  Fortunately, most men get adjusted to this feeling over time.

2.      I need to urinate:  Most men waking up from a prostatectomy will feel an overwhelming desire to urinate.  Even when they are told that they have a catheter in place draining their urine, they still feel like they have to urinate but cannot.  This uncomfortable feeling is also caused by the balloon in the bladder.  The bladder is used to nothing but urine within it at any time.  As a result, the presence of a foreign body in the bladder (the catheter/balloon) is highly irritating to the bladder.  To try to rid itself of the irritant, the bladder contracts.  Because the catheter is in place, this bladder contraction (called a bladder spasm) just pushes the urine located within the bladder out into the bag.  Because the balloon remains in place however, the bladder continues to try to expel it through repeated spasms.  In most men, this very bothersome desire to urinate goes away within a day or so.  For some men, however, the feeling persists.  Fortunately, there are pills available that can be given in the hospital and at home which relax the bladder, relieving the bladder spasms and the overwhelming desire to urinate.

3.      I have pain at the tip of my penis: This sensation is also caused by the bladder spasms described above.  Nerves travelling from the bladder to the tip of the penis are stimulated by the spasms and create pain impulses travelling down the shaft of the penis and to the tip.  Of course, the very presence of the catheter in the penis also leads to some discomfort.  Medicine for bladder spasms often decreases this pain in the penis as well.

4.      I have blood in the urine:  A small amount of blood in the urine can be normal.  After all, surgery can lead to bleeding and a prostatectomy is certainly no exception.  As a result, the urine can be light pink for a day or two after surgery.  In addition, a small amount of blood in the urine may be noticed after walking with the catheter in place.  This bleeding is caused by the balloon from the catheter rubbing on the bladder.  Nothing really needs to be done for this amount of blood in the urine.

In contrast, pure blood or clots coming out of the catheter and into the bag is a serious problem that requires immediate attention.  This is a sign of serious bleeding, usually outside of the bladder, that creeps in through gaps in the anastomosis.  Such bleeding can cause disruption of the anastomosis and actually break the bladder free from the urethra. In severe cases, such bleeding may require a return trip to the operating room to stop the bleeding and repair the anastomosis.  Often times, however, it only requires washing out the blood from the bladder by irrigating the bladder through the catheter with saline or sterile water.  In any case, significant blood in the urine is a red flag which deserves immediate attention from a physician.

5.      My catheter is not draining: This, too, can be a serious problem. While in place, a catheter is a life line for a man after prostatectomy.  It is the only conduit allowing urine to leave the body.  As a result, if the catheter malfunctions, there is no way for the urine to exit the bladder.  Sometimes, men identify a catheter malfunction when they notice that the bag into which the urine drains is empty for a prolonged period of time.  In other cases, however, a malfunctioning catheter can cause significant pain as trapped urine accumulates in the bladder and stretches it.

A malfunctioning catheter that does not drain urine is truly an emergency.  Allowing the bladder to distend too far can lead to a disruption of the anastomosis or even rupture of the bladder.  As a result, I always tell my patients that if the catheter does not work, they need to seek medical attention right away.  Because catheter malfunctions follow Murphy’s Law, they usually occur in the middle of the night, when the urologist’s office is closed.  As a result, a malfunctioning catheter often leads to a visit to the emergency room.  This is where it gets tricky.  As I mentioned before, the catheter is a life line after prostatectomy.  As such, it has to be treated with caution.  Removing the catheter prematurely or attempting to replace the catheter with another can create significant damage that may require a return to the operating room.  Such damage can cause a lifetime of incontinence.  That is why management of a malfunctioning catheter after a prostatectomy should ONLY be undertaken by an urologist.  An emergency room nurse or physician should NOT try to fix it, even if they have the best intentions.  I tell my patients to NEVER allow anyone other than an urologist to manipulate the catheter after a prostatectomy.  The stakes are just too high.

6.      I am draining urine around the catheter: Once in a while, after a prostatectomy, a patient calls me to tell me that urine is draining out of his penis around the catheter.  This problem is caused by one of two problems.  In some men, bladder spasms can be so severe that urine is expelled both through and around the catheter.  In other men, a malfunctioning catheter can distend the bladder to the point that trapped urine escapes around rather than through the catheter.  These two scenarios can often be distinguished by whether or not some urine is draining through the catheter and into the bag.  Bladder spasms will usually cause urine to drain both through and around the catheter.  A malfunctioning catheter, in contrast, will not allow drainage into the bag so urine will only be seen leaking out of the penis.  Regardless, drainage of urine around the penis should be expeditiously addressed by an urologist.

Take Home Message

The urinary catheter can make recovering from a prostatectomy a difficult endeavor.  For those men who never had to wear a catheter previously, the experience can be quite scary and foreign.  However, understanding what to expect can prevent a great deal of unnecessary anxiety.  Similarly, knowing what red flags to look for can prevent significant discomfort and complications.  In my next post, I will cover the next step in the catheter saga: what to expect when the catheter is removed.

This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

Monday, August 1, 2011

Lymph Nodes And Prostate Cancer Part II: When The Lymph Nodes Are Positive

In my last post, I discussed lymph node dissection for men undergoing prostatectomy.  Specifically, I focused on who does and does not need a lymph node dissection based on the risk of lymph node involvement by prostate cancer.  But what happens when prostate cancer is actually identified in the lymph nodes?  In the past, managing men with lymph node positive prostate cancer was not very complicated.  Most men were monitored until symptomatic spread of the cancer was noted.  After symptoms of metastatic disease emerged, palliative therapy with hormones was initiated.  The prognosis was always poor.  Today, however, the situation is quite different.  First, the prognosis is not the same for all men with lymph node positive disease but, rather, varies with the extent of lymph node involvement.  Also, therapy is usually initiated very soon after lymph node disease is diagnosed.  Finally, different treatment modalities are being implemented beyond just hormonal therapy.   In this post, I will describe these new approaches to treating men with prostate cancer in the lymph nodes.

Not All Lymph Node Positive Prostate Cancer Is The Same

When I was training to be an urologist, all men with prostate cancer found in the lymph nodes were lumped into one category.  These men were generally given a relatively poor prognosis with a 10 year survival rate ranging from 50-80% depending on whether or not they received hormonal therapy.  Recently, however, studies have demonstrated that not all lymph node disease is the same.  Men with greater than 2 lymph nodes involved by prostate cancer, for example, have been shown to have more than twice the likelihood of dying from prostate cancer as compared to those men with 2 or fewer positive lymph nodes.  After 10 years of follow up, the cancer-specific survival rates (chances of surviving prostate cancer) for these two groups were reported to be 33% and 79%, respectively.  Similar differences were noted based on the density of positive lymph nodes.  One study, for example, compared the outcomes of men in whom less than 20% of the lymph nodes removed (during a dissection) were found to harbor cancer with those of men in whom greater than or equal to 20% of the lymph nodes removed were cancerous.  The study reported that those men with the lower percentage of positive lymph nodes (<20%) enjoyed a 72% chance of living free of metastatic disease after 10 years as compared to only 47% of men with the greater density of positive lymph nodes. 

When Should You Start Treatment For Lymph Node Positive Prostate Cancer?

When prostate cancer invades the lymph nodes, it is considered to be metastatic.  As a result, as I mentioned previously, treatment for men with lymph node positive disease in the past was often delayed until symptoms were noted.  The reasoning for this treatment approach was that, because the cancer is already metastatic and hormonal therapy is palliative as opposed to curative, there is no compelling reason to start treatment right away. After all, what is the rush in treating a cancer that you cannot cure, right?  In 1999, however, a study was published in the New England Journal of Medicine, which completely refuted this line of thinking.  The study evaluated a group of about 100 men diagnosed with lymph node positive prostate cancer.  About half of these men received hormonal therapy immediately after diagnosis, while the other half did not receive treatment until they developed symptomatic metastatases.  The study reported that after 7 years, 85% of men undergoing immediate hormonal therapy were alive as opposed to only 64% of men receiving delayed therapy.  This study led to a paradigm shift in treatment.  Since that time, most men with positive lymph nodes will undergo immediate hormonal therapy.  Interestingly, however, the recent data suggesting significantly better prognoses for men with a small number of positive lymph nodes has led many experts to rethink the need for immediate hormonal therapy in all men.  Some have argued that men with minimal lymph node spread may be better served with observation rather than immediate hormonal therapy, particularly in the context of the side effects and dangers of hormonal therapy.  Unfortunately, no good data yet exists to support or refute this approach.

Is Hormonal Therapy The Only Option For Managing Lymph Node Disease?

Until recently, the answer was a resounding yes.  As I mentioned above, lymph node involvement by prostate cancer has always been considered to be metastatic disease.  As such, it has not been considered curable and any treatment has been considered palliative.  The mainstay of treatment for metastatic disease has been hormonal therapy, which works to prevent the prostate cancer from spreading further by restricting the fuel for its growth, the male hormone Testosterone. 

Recently, however, studies out of Europe have demonstrated that, when added in combination with hormonal therapy, radiation therapy can substantially increase survival in men with lymph node positive disease.  A study published just this year, for example, evaluated approximately 360 men with prostate cancer found in their lymph nodes.  Of these men, 117 underwent a combination of hormonal therapy and radiation while 247 underwent hormonal therapy alone.  The study reported that , after 10 years of follow up, men undergoing the combination therapy enjoyed a cancer specific survival rate of 86% versus only 70% for those men undergoing hormonal therapy alone.  Similarly, the overall survival rate of men undergoing the combination therapy was also higher at 10 years as compared to those undergoing hormonal therapy alone (74% versus 55%, respectively).  I should stress that the results of this study, while impressive, are by no means definitive and have not yet changed the standard treatment protocol for men with lymph node positive disease.  Nonetheless, the data provides food for thought and a topic for discussion between men with lymph node positive prostate cancer and their urologists/oncologists. 

Take Home Message

The treatment of men with prostate cancer found in their lymph nodes has undergone significant changes.  Lymph node positive disease is no longer one entity but, rather, a spectrum of diseases with varying severities and prognoses depending on the number of positive lymph nodes.  While considered metastatic disease, lymph node positive prostate cancer should still be managed early as such expedient treatment has been demonstrated to improve survival. Similarly, early data seems to support the combination of radiation with hormonal therapy in order to optimize survival outcomes for men with lymph node positive prostate cancer.  As always, men should thoroughly discuss these and other issues pertaining to the management of prostate cancer with an urologist and/or oncologist prior to making any decisions about their care.

This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

Monday, July 25, 2011

Lymph Nodes And Prostate Cancer Part I: Who Needs A Lymph Node Dissection?

When I was undergoing my training in urology, the approach to managing lymph nodes for patients with prostate cancer was pretty simple.  First, everyone undergoing a prostatectomy would also undergo a lymph node dissection. Second, anyone with proven metastases to the lymph nodes would be given a horrible prognosis and be treated with hormonal therapy.  Since that time, however, the management of lymph nodes has become much more complicated and controversial for men with prostate cancer.  Far fewer men are undergoing lymph node dissection.  Also, the management of men found to have prostate cancer in their lymph nodes is not quite as clear-cut.  In my next two posts, I will attempt to shed a little light on the controversies surrounding the evaluation and management of lymph nodes in men with prostate cancer.  In this first post, I will explain what the lymph nodes are, why they deserve our attention, and who actually needs a lymph node dissection during a prostatectomy.  In the second post, I will elaborate on the prognosis and treatment for men found to have prostate cancer in their lymph nodes.

What are lymph nodes?

The lymphatic system is a transport network for our immune system. It is a way for immune cells to move throughout the body.  When an infection occurs in a part of the body, immune cells attack the infection and then travel to local hubs called lymph nodes where they can reproduce and further target the foreign invaders.  As more immune cells travel to and reproduce in these hubs, the lymph nodes enlarge.  This is why we can actually feel tender lymph nodes around an area of infection.  For example, the lymph nodes of the neck can get swollen during an infection of the throat.  

In cases of cancer, the lymph nodes are also involved.  Cancer that spreads from its location of origin can move through either the blood vessels or the lymphatic system.  For prostate cancer, spread through the blood vessels leads to metastatic deposits in the bones while lymphatic spread leads to cancer in the lymph nodes.  These nodes are located on either side of the prostate within the pelvic cavity. 

What is a lymph node dissection?

A lymph node dissection is a surgical procedure usually performed at the start of a radical prostatectomy, which involves removing all of the lymph nodes surrounding the prostate.  This can be performed through either an open or laparoscopic (robotic) approach with equivalent success.  After removal, the lymph nodes are sent for pathologic evaluation.  The number of lymph nodes removed is quantified and the contents of the lymph nodes are inspected under a microscopic to look for the presence of metastatic prostate cancer.

One would think that by removing lymph nodes that harbor metastatic prostate cancer, a lymph node dissection could improve outcomes in the treatment of prostate cancer.  To date, however, there has been no significant evidence demonstrating that the removal of pelvic lymph nodes changes the prognosis for men undergoing treatment for prostate cancer, whether or not prostate cancer is found in the nodes.  If lymph node dissection provides no therapeutic benefit, why go through the trouble of performing it?

Why is a lymph node dissection important?

When prostate cancer spreads to the lymph nodes, the entire approach to treatment changes.  First, the presence of prostate cancer in the lymph nodes means that the prostate cancer is no longer curable.  The prognosis is significantly worse for men with positive lymph nodes.  As a shall describe in the next post, the prognosis varies considerably depending on how many lymph nodes are involved as well as the density of positive lymph nodes.  This information is critical in counseling and in medical decision making.   In addition, as I shall also discuss in the next post, the presence of positive lymph nodes calls for the early administration of hormonal therapy.  If such treatment is not promptly initiated because the presence of prostate cancer within the lymph nodes is not revealed, the prognosis can be substantially worse.

At this point you are probably asking yourself a very logical question.  If the lymph node dissection is only valuable from a diagnostic perspective, aren’t there less invasive ways to find out if prostate cancer has spread to the lymph nodes?  The answer is not really.  Mainstream imaging modalities such as CT scans and MRIs are only able to detect prostate cancer in the lymph nodes in approximately 20-30% of cases.  The reason for this is the fact that the resolution of these techniques is around 1cm.  That means that unless a cancerous lymph node has reached 1 cm in size, a CT scan or MRI cannot detect it.  As a result, most lymph nodes, which are often less than 1cm in size, go undetected.  PET scans, as well, have not been very helpful in detecting occult prostate cancer in lymph nodes for this and other reasons.  New technology has been developed which can increase the ability to detect cancerous lymph nodes with an accuracy of 80-90%.  This technique uses a special contrast medium composed of nanoparticles that have an affinity for lymph nodes.  Called Combidex in the United States and Sinerem in Europe, this contrast medium has demonstrated amazing success in detecting prostate cancer within the pelvic lymph nodes when used in conjunction with standard imaging techniques.  For reasons that I have not yet unearthed, however, this new technique has not been approved for use in the United States and, I believe, the manufacturer may have even stopped producing it.  

Why aren’t lymph node dissections routinely performed as part of prostatectomies?

If non-invasive imaging techniques are not sensitive enough to detect most cancerous lymph nodes, shouldn’t every man undergoing a prostatectomy also undergo a lymph node dissection.  After all, if the surgeon is working in that area already and the dissection can provide important information that can change the treatment plan, it only makes sense to perform a lymph node dissection on everyone, right?  In medicine, like in all other aspects of life, there is no free lunch.  A lymph node dissection, like any other surgery, has potential serious complications that need to be weighed against the potential benefits of the dissection.  The reported complication rates for pelvic lymph node dissections have ranged from 2-20% depending on the extent of the dissection performed.  The most common complications include:

1. Lymphocele formation:  during a lymph node dissection, numerous little lymphatic channels are clipped off and cut.  Occasionally these channels are not appropriately sealed and can leak lymphatic fluid into the pelvis.  This fluid can accumulate and form a collection called a lymphocele.  These collections of lymphatic fluid can grow quite large, compressing nearby structures like blood vessels (which can cause swelling of the legs), the bladder (causing trouble with urination) and the intestines (causing bloating).  Lymphoceles are treated by placing a temporary drain which allows the fluid to leave the pelvis.  Occasionally, more invasive surgical intervention is required as well.
2. Nerve injury: one of the boundaries of a lymph node dissection is the Obturator nerve.  This nerve provides impulses to the leg, which causes it to move inward or towards the midline of the body.  During a lymph node dissection, this nerve can be inadvertently injured or cut.  Such damage can impair the movement of the leg on that side of the body, which can significantly affect the ability to walk or drive a car.  Some sensation is also affected by damage to this nerve.
3. Blood vessel injury:  another boundary of a pelvic lymph node dissection is the external iliac vein.  This is one of the main veins of the body, which drains blood from the legs and feet back to the heart.  Occasionally a tear in this vein can occur which can lead to significant loss of blood during surgery.  In addition, compression of the vein during the procedure can lead to a large blood clot called a deep vein thrombosis or DVT.  Such a clot can cause swelling of the leg and foot and severe pain.  Occasionally, the clot can even travel to the lungs and cause a life threatening condition called a pulmonary embolism.

Understanding these potential complications, one can see why lymph node dissections should not be taken lightly and should certainly be performed only when necessary.  The question, of course, becomes when is the dissection necessary?

Who needs a lymph node dissection?

To answer this question we must first determine who is at greatest risk of harboring occult, metastatic prostate cancer within their lymph nodes. Overall, only about 4-5% of men with prostate cancer have lymph node positive disease.  However, this rate greatly depends on other characteristics of a given prostate cancer.  Men with low risk prostate cancer, for example, have rarely been found to have lymph node disease.  As I described in a previous post, low risk disease is characterized by a Gleason score of 6 or less, a PSA less than 10 and no to minimal cancer felt on rectal exam.  Studies have shown that men with prostate cancer meeting these criteria  harbored occult lymph node disease in less than 1% of cases, on average.  Men with more extensive prostate cancer are much more likely to have positive lymph nodes.  For example, men with a PSA score greater than 10 have been found to have lymph node involvement in 7-29% of cases, depending on the Gleason score and rectal exam findings.  Similarly, a man with a PSA of 7 or greater has a significantly higher chance of lymph node involvement, even when the PSA is less than 10. One study of men with prostate cancer and a PSA <10, for example, reported lymph node involvement in 3% of men with a Gleason score of 6 as opposed to 25% for those men with a Gleason score of 7 or higher.  Several tools have been developed to help determine a particular man’s chance of harboring lymph node metastasis.  One such tool, called the Partin Tables, uses a patient’s PSA, Gleason score, and rectal exam findings to make this determination.  This tool is available to the public through the Johns Hopkins website at:

Using such tools, patients and urologists can understand the risk of lymph node metastases and, with this knowledge, make the determination of whether or not to proceed with lymph node dissection.  While no hard and fast rules exist as to when lymph node dissection should be performed, most urologists use similar criteria.  Low risk patients, for example, rarely if ever undergo the dissection.  In contrast, men with a Gleason score above 6 and/or a PSA above 10 almost always have their lymph nodes removed.  Some urologists also rely on a cutoff risk of 7% (as predicted by the tools described above) of lymph node metastasis, above which they routinely perform a lymph node dissection.  

Take Home Message

The lymph node dissection can provide important information that can lead to significant changes in the management of prostate cancer.  Removal of the pelvic lymph nodes, however, is not risk free and should not be routinely performed in all men treated for prostate cancer.  Rather, the decision of whether or not to perform a lymph node dissection should be determined based on the risk of lymph node metastasis as ascertained from a prediction tool.

This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

Monday, July 18, 2011

Bladder Neck Contractures After Prostatectomy

Men undergoing radical prostatectomy need to be aware of a potentially serious complication called a bladder neck contracture.  This narrowing at the connection between the bladder and urethra can cause significant symptoms including a slow stream and incontinence.  These symptoms are often ignored until full retention of urine occurs.  In this post I discuss bladder neck contractures, their etiology, and how to treat them.

What is a Bladder Neck Contracture?

The prostate is usually located between the bladder and the urethra.  I often describe the relationship to patients in the following manner: the bladder is like an upside down fishbowl which is connected to a donut (the prostate) which is subsequently connected to a straw (the urethra).  Urine leaving the bladder goes through the donut hole of the prostate and out the urethra.  During a prostatectomy, the prostate is removed, requiring this plumbing to be rerouted.  In order to do this, the “neck” of the bladder, which was previously attached to the prostate, is sewn directly to the urethra tube.  In 2-20% of cases, that connection gets scarred down to form a bladder neck contracture.  The extent of this contracture can be variable, ranging from a mild narrowing to a complete obliteration of the connection.  Either way, a bladder neck contraction can create significant difficulty with the passage of urine from the bladder to the urethra.

What Causes a Bladder Neck Contracture?

While the true causes of bladder neck contractures have not been definitively elucidated, numerous theories have been presented.  The two most popular explanations include:

1) Gaps in anastomosis:  When the anastomosis (the surgically created connection between the bladder neck and urethra) is made during a prostatectomy, several problems can occur.  First, the sutures placed in the bladder or urethra can tear.  Also, bleeding from the surgery can create a large clot called a hematoma which can insinuate itself between the stiches and stretch the anastomosis.  Either of these situations will create gaps in the anastomosis between the bladder neck and urethra.  The human body has a natural tendency to fill gaps with fibrotic tissues or scar.  As a result, gaps in the anastomosis allow scar tissue to form which, in turn, creates a bladder neck contracture.
2) Poor blood supply:  Many urologists have postulated that bladder neck contractures occur due to decreased blood supply to the anastomosis.  Generally, when a tube or connection in the body does not get an adequate supply of oxygen-rich blood, it gets obliterated by scar tissue.  This situation, the theory proposes, is exactly what creates a bladder neck contracture.  So what causes poor blood supply to the anastomosis?  Several factors have been implicated.  First, tying down the sutures connecting the bladder and urethra too tightly can strangulate the blood vessels to the area and decrease the flow of blood.  Others have argued that prostatectomies performed without nerve sparing can also decrease blood supply to the area.  Finally, some men are simply predisposed to problems with blood vessels.  Men with diabetes, high cholesterol, and heart disease, for example, demonstrate poor blood flow to all parts of the body, including the anastomosis.  Not surprisingly, older men (who are more prone to problems of blood flow) are more likely to experience bladder neck contractures than their younger peers.

What are the Signs of a Bladder Neck Contracture?

Men usually start to experience symptoms from a bladder neck contracture between 3-6 months after surgery.  The initial symptom in most men is a subtle slowing of the urinary stream.  This symptom is often ignored until it gets substantially more dramatic.  Often times, men actually complain of urinary incontinence after a period of dryness following radical prostatectomy.  This leakage is due to the overflow of urine from a bladder distended with urine that is barely able to escape into the urethra.  Eventually, if left unattended, bladder neck contractures lead to complete urinary retention.  Unable to urinate, men present to the emergency room where doctors and nurses are usually unable to negotiate a catheter into the bladder due to the narrowing from the contracture.  At this point, an urologist needs to be called to provide treatment.

How Are Bladder Neck Contractures Treated?

Men complaining of symptoms suggestive of a bladder neck contracture first need to be evaluated with a cystoscopy.  This procedure, done in the urologist’s office with local anesthesia, involves passing a flexible camera through the penis and towards the bladder.  With this camera, an urologist can tell if there is any scar tissue creating a blockage at the anastomosis between the bladder and urethra.  In addition, he can determine if there are any other problems in the bladder or urethra that could be mimicking these symptoms.

If a bladder neck contracture is confirmed during an office cystoscopy, a decision then needs to be made to determine how to proceed.  One option is to perform a gentle dilation at that time under local anesthesia.  A dilation is performed with the use of a variety of tubes of varying diameters.  The urologist starts by passing the smallest tube through the contracture and into the bladder.  He then stretches the contracture by passing larger and larger tubes through it until a catheter (like the one in place after prostatectomy) can be successfully placed in the bladder.  This catheter usually stays in place for a few days and is then removed.

 Although definitely tolerable, a dilation performed under local anesthesia can be uncomfortable.  As a result, some men choose to have their bladder neck contractures treated in the operating room under more extensive anesthesia.  In the operating room, more extensive procedures can be offered besides just dilation.  For example, a larger camera can be advanced to the location of the contracture and a knife (within the camera) can be used to cut the contracture.  This procedure also requires a catheter for a few days.

Regardless of which procedure is chosen, bladder neck contractures are successfully managed with a single treatment in 60-80% of cases.  Some men, however, have very tough contractions that recur soon after treatment.  For these men, more aggressive operative therapy is needed.  One such therapy involves aggressively and deeply cutting the contracture with a hot knife, also through an endoscopic approach using the camera.  If this does not work, some surgeons use a permanent, metallic stent (called Urolume) which can be deployed across the contracture.  These aggressive treatments usually lead to significant incontinence.  As a result, most men that are successfully treated with such aggressive options subsequently also need to undergo placement of an artificial urinary sphincter (AUS) to help them overcome the leakage of urine.  I describe the AUS in detail in my previous post on surgical options for urinary incontinence after prostatectomy:

Take Home Message

Bladder neck contractures develop in a small proportion of men undergoing radical prostatectomy for prostate cancer.  Presenting 3-6 months after surgery, this scar tissue at the connection between the bladder and urethra often causes slow stream and occasionally retention of urine.  In some men, it can also cause urinary incontinence.  Men with these symptoms after prostatectomy should seek expedient evaluation and, if necessary, treatment for bladder neck contracture from their urologist.  Such proactive management can save a great deal of potential stress and discomfort during a late night visit to the emergency room .

This blog is not a medical practice and cannot provide specific medical advice. This information should never be used to replace or discount the medical advice you receive from your physician

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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