Wednesday, April 27, 2011

Hormonal Therapy For Prostate Cancer: Understanding The Risks To Your Heart

If you have been diagnosed with prostate cancer, chances are you have been told about hormonal therapy.  Nearly 70 years ago, the management of prostate cancer was revolutionized by the discovery that prostate cancer is fueled by the male hormone testosterone.  Prior to this discovery, numerous men languished in hospital beds suffering from the pain of advanced prostate cancer.  After the discovery, men with advanced prostate cancer started undergoing orchiectomy (surgical removal of the testicles).  Because the testicles naturally produce most of the testosterone in men, removing them effectively removes most of the testosterone from the body.  With the “food” gone, the prostate cancer moves much more slowly and sometimes decreases in size.  While not a cure, such hormonal manipulation has led to significantly decreased symptoms for men with advanced prostate cancer.

Hormonal therapy was further advanced about 30 years ago with the development of “medical castration.”  Rather than removing the testicles, doctors could give medicine which would effectively prevent the body from producing testosterone.  This approach was significantly more appealing for most men as it avoided the psychological trauma of castration.  Initially, medical castration or hormonal therapy was used just for men with prostate cancer which had spread to the bones and other distant organs.  Studies demonstrated that the treatment, although not a cure, could allow men with metastatic prostate cancer to live symptom free for many years.  More recently, the use of hormonal therapy has been further expanded to men with localized disease.  Numerous studies demonstrated that hormonal therapy given in combination with radiation therapy for men with locally advanced prostate cancer is superior to radiation alone.  As a result many doctors now give at least a short course of hormonal therapy at the start of radiation therapy while others give hormonal therapy up to 2 years following radiation therapy for men with localized disease.  Other doctors also give early hormonal therapy for men with a PSA recurrence after radical prostatectomy.  With these expanded indications, more and more men are currently treated with hormonal therapy. 

The problem with such widespread use of hormonal therapy is that this treatment modality, like all medicines, is no free lunch.  As more and more men have been treated with hormonal therapy, more and more risks have been discovered.  The risk of osteoporosis, for example, is very well known to urologists and patients alike and is often very carefully monitored and treated.  Recently, however, the very real impact of hormonal therapy on the heart has been demonstrated.  Studies have demonstrated that treatment with hormonal therapy often leads to metabolic changes such as increases in blood sugar and cholesterol.  As a result, a very real increase in heart attacks and heart related deaths have been attributed to the use of hormonal therapy.  While radiation oncologists and urologists are very well trained to evaluate and treat prostate cancer, they are generally not as great at looking at the big picture.  As a result, the treatment of prostate cancer often takes priority over heart health, particularly when a primary care doctor is not part of the decision making process.  The goal of this post is to review the real metabolic consequences of hormonal therapy and the subsequent heart risks that they then create.

Metabolic Consequences of Hormonal Therapy

  1. Blood Sugar:  The loss of testosterone and estrogen due to hormonal therapy has been demonstrated to cause a resistance to the hormone Insulin.  Insulin is the prime regulator of blood sugar in the body.  As a result, men who start hormonal therapy often demonstrate a rise in their blood sugar and Hemoglobin A1C (a measure of diabetes control).  As a result, studies have demonstrated that men undergoing hormonal therapy have a 28-50% HIGHER risk of developing diabetes than equally aged men not receiving the treatment.

  1. Lipids:  Hormonal therapy has also been demonstrated to have a significant impact on lipids (fats) in the blood stream.  One study evaluating men on hormonal therapy demonstrated that after about a year on therapy, these men demonstrated an increase in total cholesterol of 9% and an increase in triglycerides (fat in the bloodstream) of 26%. 

  1. Arterial Stiffness:  The decrease in testosterone experienced during hormonal therapy has also been thought to increase the stiffness of the arteries carrying blood to the heart.  This increased stiffness is thought to decrease blood flow to the heart and potentially cause a heart attack.

Hormonal Therapy and Risks to the Heart

With the metabolic changes mentioned above, it probably does not seem surprising that studies have demonstrated that taking hormonal therapy may pose a substantial risk to the heart.  Large studies ( 37,000- 73,000 men) have demonstrated that hormonal therapy results in a 16-19% increased risk of coronary artery disease, an 11-28% increased risk of heart attack, and a 16-35% increased risk of sudden death when compared with men not undergoing the treatment.  Another study demonstrated a 20% increased risk of heart complications within 1 year of starting hormonal therapy.  Not surprisingly, higher risk was seen in older men, with one study demonstrating that men over age 65 undergoing hormonal therapy have over 2 times the risk of heart related death within 5 years of starting therapy (5.5% vs 2%) as compared with those that do not undergo the therapy.

The impact of hormonal therapy for men with preexisting heart disease is even more dramatic.  A recent study published in the Journal of the American Medical Association studied men with localized prostate cancer undergoing 4 months of hormonal therapy in combination with radiation therapy.  The study specifically looked at men with a prior history of a heart attack or heart failure.  In this group, the study found that 26% of men undergoing hormonal therapy died within an average of 5 years as compared to 11% of men who did not undergo the therapy.  That represents TWICE the risk of death for men with prior heart disease who underwent hormonal therapy plus radiation therapy as compared to the men that underwent radiation therapy alone.  Interestingly, the authors of the study did not demonstrate an increased risk of death for those men undergoing hormonal therapy who did not have significant underlying heart disease or risk factors for heart disease. 

Take Home Message

So what do we conclude from this worrisome information?  Should hormonal therapy no longer be offered to men with prostate cancer?  Should men already on hormonal therapy stop the treatment?  Of course not.  Hormonal therapy has been vital in the fight against prostate cancer, particularly for men with advanced disease.  Instead, this data should make us rethink who should receive hormonal therapy and what precautions should be taken when the therapy is administered.  The problem with many urologists and radiation oncologists is that they often get caught up with prostate cancer and, sometimes, miss the big picture.  While they see the potential benefits of hormonal therapy in terms of prostate cancer, they don’t pay enough attention to the impacts of this treatment on other vital aspects of a patient’s health.  As a result, as the patient, you need to make sure that a few steps get taken prior to proceeding with hormonal therapy:

  1. Tailor Your Prostate Cancer Treatment To YOU:  Not ALL men need hormonal therapy to treat prostate cancer, particularly localized prostate cancer that has not spread. While, indeed, studies have demonstrated improved outcomes with the addition of hormonal therapy to radiation therapy for aggressive, localized disease, the extent of these benefits need to be weighed against the potential risks.  For example, older men with significant heart problems (or risk factors for heart disease) and low grade prostate cancer, may want to consider avoiding hormonal therapy in conjunction with radiation.  They will probably do just as well from the cancer standpoint while avoiding the heart risks.  At the very least, you should have your doctor go over the specific risks and benefits of hormonal therapy in your particular situation.

  1. Assemble Your Team: Some men really need hormonal therapy in treating their prostate cancer.  If you are one of those men, make sure that your ENTIRE medical team is involved.  Most men who undergo hormonal therapy are managed for this by just their urologist and/or radiation oncologist.  The problem with this arrangement, as I mentioned before, is that while these specialists are great at managing prostate cancer, they are not quite as adept at taking care of diabetes, cholesterol, and heart disease.  As a result, if you are started on hormonal therapy, you may want to make sure that you are followed by your primary doctor as well.  Your primary doctor can check baseline labs like blood sugar and cholesterol levels as well as a baseline blood pressure. He or she can then check on you every 3-4 months with repeat labs and exams to see if you are experiencing any of the metabolic changes described above and make appropriate adjustments to your other medicines, if necessary.  If you already have heart disease, you may want to discuss hormonal therapy with your cardiologist prior to starting and to have him or her follow you to look for any early changes to your heart as a result of the therapy. Because the damage done by hormonal therapy usually occurs in the first year of treatment, this rigorous follow up only needs to be carried out for a short period of time.  Having a COMPLETE team follow you, however, may be the key to avoiding serious heart problems for years to come.

  1. Change Your Lifestyle:  I am sure most if not all of you have heard of simple ways you can decrease your risk of developing heart disease.  These lifestyle modifications become particularly important when on hormonal therapy.  Simple changes to your diet like decreasing the amounts of fat and sugar you consume can go a long way in battling the metabolic changes brought about by hormonal therapy.  In addition, any amount of aerobic exercise such as walking can decrease the risk of heart problems in the future.  As always, make sure you carry out any diet or exercise regimens under the supervision of your doctor, particularly if you already have heart disease.

As with many other aspects of prostate cancer treatment I have discussed on this blog, hormonal therapy, again, proves that there is no such thing as a free lunch.  While hormonal therapy has been shown to be beneficial for many patients with varying extents of prostate cancer, this benefit does not come without risk.  The development of significant heart disease can negate any prostate cancer benefits in SOME men.  As a result, before agreeing to hormonal therapy, make sure that your doctor weighs the relative risks and benefits in YOUR case.  If you and your doctor conclude that hormonal therapy is right for you, make sure that you put together the right team and plan to manage the potential risks.  As a urologist, I am committed to battling prostate cancer with all the medical and surgical tools available to me.  As a patient, you need to make sure that your doctors keep your overall health in mind while fighting this battle.

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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, April 20, 2011

High Risk Prostate Cancer After Prostatectomy: Radiate or Wait?

The findings of a pathology report after a radical prostatectomy can be critical in determining outcomes for men with prostate cancer.  In these reports, pathologists describe key aspects of the prostate cancer including how aggressive it looks under the microscope and if it has spread outside of the boundaries of the prostate.  The pathologist also comments on whether the cancer was removed in its entirety or whether the surgeon cut across the cancer at one or more sites.  This information is not only critical in determining prognosis but, also, in determining if and when the patient may need supplemental radiation therapy.  In this post I will describe the “high risk” pathologic features and explain the necessity and timing of radiation therapy for men who have one or more of these features on their pathology report.

High Risk Pathologic Features

Upon reviewing the pathology report after a prostatectomy for prostate cancer, four characteristics are critical to determine about the prostate specimen that was removed:

  1. Extracapsular Extension(ECE):  The prostate is normally covered on all of its surfaces by a lining called the capsule.  The pathology report will state if this capsule is intact and whether any cancer appears to be extending beyond it.  If prostate cancer has already spread beyond the capsule at the time of surgery, chances are higher that some cancer moved beyond the prostate and was left behind.

  1. Seminal Vesicle Invasion:  The seminal vesicles are a pair of glands that are situated above and behind the prostate gland.  They are responsible for producing part of the semen that is ejaculated during sex.  Occasionally, prostate cancer spreads from the prostate to the seminal vesicles.  This invasion is considered a poor prognostic sign.  Involvement of the seminal vesicles is often associated with metastatic and/or locally recurrent prostate cancer after prostatectomy.

  1. Positive Margins:   When the pathologist reviews a prostatectomy specimen, a key feature that he looks for is the status of the margins.  The pathologist looks at all of the cut surfaces and determines whether any prostate cancer is seen at these surfaces.  Sometimes a positive margin cannot be avoided due to prostate cancer that extends well beyond the boundaries of the prostate.  In other cases, the margin is positive due to technical errors during surgery in which parts of the prostate (and cancer) were left behind.  In either case, positive surgical margins often result in a higher rate of local recurrence of prostate cancer.  Of note, not all positive margins are considered high risk.  I will explore this topic in a future post.

  1. Gleason Score: As mentioned in numerous prior posts, the Gleason score is a measure of how aggressive prostate cancer looks under the microscope.  Higher Gleason scores( greater than 7) are associated with a higher chance of local and distant recurrence after surgery and of an overall worse prognosis.

The presence of these adverse factors on a prostate biopsy portends a much higher chance of recurrent cancer.  Studies have demonstrated that 40-50% of men with combinations of these factors will have PSA relapse.  This statistic is important because up to a third of men with PSA recurrence will develop metastatic disease within 8 years and 17% of these men will die of prostate cancer within 15 years.  The increased risk posed by these adverse pathologic factors led to the question of whether men with such features would benefit from immediate radiation therapy after prostatectomy.

Adjuvant Radiation Therapy

Numerous studies have been performed to determine whether patients with high risk pathologic factors would benefit from radiation therapy immediately after prostatectomy.  Called adjuvant radiation therapy, this type of treatment is usually instituted starting approximately 3-4 months following prostatectomy.  One of the biggest studies evaluating adjuvant radiation therapy after prostatectomy was conducted by the Southwest Oncology Group (SWOG) and published in 2009.  The study evaluated 425 men determined to have the adverse pathologic factors noted above after radical prostatectomy.  In this study, half of the men were randomly assigned to undergo adjuvant radiation therapy and half were assigned to observation.  For those men undergoing observation, initiation of treatment (with radiation, hormonal therapy, or both) was usually stimulated by a rising PSA and was done at the discretion of the treating doctor. 

The SWOG study yielded some very impressive results supporting adjuvant radiation therapy.  The study demonstrated that men treated with adjuvant radiation therapy were only half as likely to have a PSA recurrence as compared to those men simply followed with observation.  After over 12 years of follow up, this translated into a 38% decreased risk of metastatic disease.  In addition, the implementation of adjuvant radiation therapy resulted in an approximately 8% higher chance of survival (74% vs 66%) at 10 years after treatment.

While the SWOG study made a strong argument for starting radiation therapy after prostatectomy for those men with high risk pathologic features, it also created some doubt.  The study had several limitations, one of the most important of which was that not all men in the observation arm actually got radiation after a PSA recurrence.  In fact, only 33% of patients who had a PSA recurrence underwent such delayed or salvage radiation therapy at the time of recurrence. This problem begged the question of whether adjuvant radiation therapy is really necessary or if, in fact, radiation therapy could be delayed until PSA recurrence is noted.

Salvage Radiotherapy

While no notable  prospective studies have been completed which directly compare adjuvant to salvage radiation therapy in men with pathologically high risk prostate cancer, numerous studies have evaluated salvage therapy in isolation.  A very widely cited study performed in 2007 retrospectively evaluated the outcomes of salvage radiation therapy in 500 patients with adverse pathologic factors after prostatectomy for prostate cancer.  The study demonstrated that men undergoing radiation therapy shortly AFTER PSA RECURRENCE demonstrated some good outcomes.  For example, the study reported that men with positive margins and a Gleason score less than or equal to 7 had a 61% chance of no progression after a PSA recurrence if salvage radiation was instituted at a PSA level less than or equal to 2.  In addition, the study demonstrated that, if implemented at a recurrent PSA level less than or equal to 0.5, salvage therapy resulted in no signs of disease in 48% of all men treated.

While also not perfect, this study led many urologists to question the need for immediate or adjuvant radiation therapy for patients with adverse pathologic findings on prostatectomy specimens.  Given the fact that the SWOG study determined that adjuvant therapy yielded a survival benefit in only 1 in12 men treated, many urologists argued that it would be more prudent to wait until PSA recurrence to begin radiation therapy. This argument was strengthened by the fact that radiation therapy is, of course, not without its own risks and side effects.  Studies have demonstrated that radiation can lead to injury to the rectum and bladder, occasionally causing diarrhea, blood in the urine and/or stool, urinary frequency and urgency, and pain.  In addition, radiation may cause scar tissue in the urethra tube.  Some have argued that radiation therapy administered soon after prostatectomy can also lead to decreased urinary control although studies have not shown this to be true.  As a result, common practice today is to closely monitor men with high risk pathologic features after prostatectomy and to give salvage radiation therapy upon the first signs of PSA recurrence.

While the policy of administering salvage radiation therapy for men with high risk pathologic features has been relatively successful, it really leaves the question of whether SOME men are losing some survival benefit by not getting adjuvant radiation therapy.  A study published last year by a very respected radiation oncologist ( Anthony D’Amico, MD) and urologist( Judd Moul, MD) tried to answer this question through a retrospective evaluation of over 1600 men undergoing radical prostatectomy for high risk prostate cancer at Duke University.  The study classified men with adverse pathologic features into those with T3 disease( extracapsular extension{ECE} or positive seminal vesicles), Gleason score 8-10, and positive margins. The study then compared men that underwent immediate adjuvant radiation with those that underwent salvage radiation only after PSA recurrence.  The study found that for those men who had only one adverse feature (for example a positive margin but with no ECE or seminal vesicle involvement and Gleason score less than or equal to 7), only 18% of the 587 men observed after prostatectomy demonstrated a PSA recurrence after 8 years of follow up.  Of these men that had a PSA recurrence AND got salvage radiation therapy at the time of recurrence, NONE died from prostate cancer after 9 years of follow up.  The study concluded that while men with multiple adverse pathologic factors should be considered for adjuvant therapy, those with a single adverse factor can reserve radiation therapy for a PSA recurrence, avoiding unnecessary radiation in 80% of cases without any increased risk of death from prostate cancer in the long term.

As you can see, deciding what to do about high risk pathologic features after prostatectomy can be very controversial.  Reviewing the pathology report with your urologist after surgery is critical.  Identifying high risk features in the report can help you determine your overall risk for recurrence and help guide you toward appropriate supplemental therapy if and when it is indicated.

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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, April 13, 2011

Prostatectomy Complications: Risks To Know About

Deciding to proceed with surgery to cure cancer can be a daunting task.  This decision can be even more difficult in the case of prostate cancer.  With so many treatment options available and, for some, even a viable option of not treating the cancer, the decision to go ahead with prostatectomy is certainly not one that anyone takes lightly.  As a result, when counseling my patients about surgery and other treatment options for prostate cancer, I try to be very thorough about explaining all the potential risks of the procedure.  That way, they really have an understanding of what they can be potentially getting themselves into.  The purpose of this post is to review the various risks of prostatectomy, both traditional and robotic.  Many of the risks of these two types of surgery are identical.  However, I will point out any disparity in risks between the two surgeries when, in fact, there is one. For the purpose of clarity, I have divided the complications into three types: 

  1. Intra-operative
  2. Postoperative
  3. Long Term

Intra-operative Complications: These are the problems that could potentially occur at the time of surgery.

1.      Bleeding:  Radical prostatectomy, the traditional surgery for prostate cancer, has always been associated with bleeding.  As the procedure has been refined, the average blood loss has decreased but remains significant.  On average, a radical prostatectomy tends to result in a loss of about 500-900 milliliters of blood.  While young, healthy people can usually tolerate such blood loss without any untoward effects, older, sicker men may not tolerate this type of blood loss as well.  As a result, most men that undergo traditional surgery donate a unit of their own blood a few weeks prior to surgery so that they may receive it back at the time of surgery and not need to rely on blood from the blood bank ( with its associated very low risk of communicable diseases).  Robotic surgery, in contrast, usually results in significantly less bleeding (about 100-200 milliliters).  This difference is accounted for by the fact that the robotic surgery involves a process called insufflation in which the abdominal cavity is stretched with gas to allow for room for the surgeon to see and work.  This gas creates pressure which stops minor bleeding from veins that would otherwise bleed freely during open surgery.  As a result of this decreased bleeding risk, many robotic surgeons do not request patients to donate blood prior to the procedure.

2.      Damage to the bladder or ureters: Because the bladder sits right on top of the prostate, removal of the prostate sometimes leads to injury of the bladder.  Most of these injuries are pretty minor and can be fixed at the time of surgery pretty easily.  One injury that is a little more complicated is the type that occurs to the ureters, the tubes that carry urine from the kidneys to the bladder.  Sometimes, during prostatectomy, the surgeon inadvertently cuts the ureter or the opening of the ureter into the bladder.  If this occurs, the surgeon would need to repair this injury by reconnecting the ureter tube to another location in the bladder.  This type of procedure, called ureteral reimplantation, is something that urologists are very comfortable doing and, so, usually does not result in any long term problems after surgery.

3.      Damage to the Rectum: For those of you who have had a prostate biopsy, you probably remember that the biopsy was done through the rectum.  The reason for this approach is that the rectum sits right behind the prostate and is separated from it by a thin lining of tissue.  During a prostatectomy, the prostate is occasionally very stuck to the rectum and, upon trying to separate the prostate from the rectum, the surgeon can make a hole in the rectum.  If the hole is small and the patient has had a bowel preparation (enemas and oral laxatives) the surgeon can often just repair the hole with some stitches.  If the hole is big or the patient has not had a bowel preparation, however, a colostomy occasionally needs to be performed.  A colostomy is a procedure where the colon is separated from the rectum (where the hole is) and brought out to the skin to a bag.  The stool is collected in a bag and prevented from going down to where the hole in the rectum is located, allowing the hole to heal.  After a few months, a surgeon can then reverse the colostomy by reattaching the colon back down to the rectum and allowing the patient to, once again, have normal bowel movements.  Fortunately, this type of complication occurs less frequently than 1% of the time.  However, this is not much consolation if you are one of those few people who have to defecate into a bag for a few months. 

4.      Complications of Anesthesia:  Any surgery requiring general anesthesia carries the risk of serious complications related to the anesthesia.  These potential problems include heart attack, stroke, a blood clot in the lungs, aspiration of stomach contents (i.e. food) into the lungs, and even death.  Prevention of these complications requires a thorough evaluation prior to surgery to assess medical and anesthesia risks.

Postoperative Complications: Even when a prostatectomy is carried out without a hitch, occasional problems can be noted from the time immediately following surgery to a few weeks following surgery.

1.        Infection:  Infections are not a common problem after prostate cancer surgery.  With adequate antibiotics around the time of surgery, most patients do quite well in avoiding infections.  For some patients, however, infections do occur.  Most commonly, an infection occurs in the incision, making it red, hot, and occasionally leaking pus.  For others, infections can occur in the urine as demonstrated by cloudy or bloody urine and pain over the bladder.  Both of these types of infections can be successfully managed with antibiotics.

2.        Hematoma: Sometimes bleeding is not noted at the time of surgery, allowing blood to accumulate over time within the area where the surgery was performed.  This large accumulation of blood and clot is called a hematoma.  While such collections are sometimes not even noticed by patients, occasionally they can cause a great deal of pain and discomfort.  Rarely, they can even push so much on the bladder as to tear the anastamosis (the surgical connection made between the bladder and urethra tube).  This can be a very serous complication requiring surgery to re-establish the connection.  Many times, however, less severe hematomas can be managed conservatively with rest, pain medicine, and time.

3.        Wound Issues:  The most common problem with surgical wounds is infection (as described above).  Less commonly, wounds can start draining fluid. Occasionally this leakage is due to a fluid collection the builds up underneath the skin called a seroma.  This usually needs to be drained by your surgeon in the office.  More rarely, the leakage can be due to a tear in the deep closure of the wound.  This type of leakage may require a return visit to the operating room to re-close the deep parts of the wound.  Either way, leakage from the wound should ALWAYS be reported to your surgeon. 

4.        Catheter Malfunction:  After prostate surgery, the catheter in place which drains urine from the bladder really serves as a lifeline for the bladder.  If the catheter stops working, there is no way for the urine to drain.  Removing or replacing the catheter incorrectly can jeopardize the anastamosis between the bladder and the urethra, resulting in the potential need for repeat surgery and severe, chronic leakage of urine.  As a result, I tell my patients after prostatectomy that the ONLY person who should remove or replace a urinary catheter in a man after prostate cancer surgery should be a urologist.

5.        Bloody Urine:  Occasionally, for a few days after prostatectomy, blood in the urine could be noted.  This can be due to irritation of the bladder from the catheter or to some minor oozing after surgery.  Either way, this blood in the urine can usually be managed conservatively, with periodic flushing of the catheter with saline.  Rarely does blood in the urine remain a long term problem.

6.        Blood Clots in Leg Veins:  Any surgery that involves a patient lying down for prolonged periods of time could predispose him to blood clots in the veins of the legs.  This is especially true of surgeries performed in the pelvis, like prostatectomies.  A blood clot in a leg vein, otherwise known as a deep vein thrombosis (DVT), often presents itself as pain in the calf or behind the knee, swelling of the calf or leg, or redness of the leg.  Men with these symptoms after prostate surgery should notify their surgeon or another medical doctor immediately because these clots can progress and travel to the lungs, which can be fatal.  Once diagnosed through an ultrasound of the leg, a DVT is treated with several months of blood thinning medication.

Long Term Complications:  While the complications mentioned above sound frightening, they fortunately occur fairly rarely.  Long term complications, in contrast, occur much more frequently BUT are a lot less scary.

1.      Impotence:  About half of men undergoing prostatectomy develop erectile dysfunction following surgery.  Younger men and those with strong erections prior to surgery are more likely to maintain some erections after surgery.  Regardless of the extent of impotence after surgery, most men are able to sustain erections again after surgery with the variety of treatment options available for this problem.  I have covered the management of erectile dysfunction following prostatectomy in a previous post and you are welcome to review it if you are interested:

2.      Incontinence:  Leakage of urine is also a common occurrence after prostatectomy.  Incontinence occurs because the mechanism that controls urination is intimately associated with the prostate.  During a prostatectomy, when the prostate is removed, this mechanism can be damaged, leading to leakage of urine in the short or long term.  Approximately 15% of men demonstrate long term incontinence after prostatectomy.  Most men are able to become dry with a combination of Kegel exercises and time.  Kegel exercises are performed by squeezing the muscle that you normally use to hold in urine when you have the strong desire to urinate.  I advise my patients to perform these exercises even PRIOR to surgery and to continue performing them over 100 times per day following surgery.  I have found that men that start early and are diligent with the exercises tend to regain their continence sooner and more effectively.  Urinary leakage can continue for months after surgery.  By about 6 months to a year, most men have attained a level of dryness that will most likely remain chronically.  For most men, this usually means either complete dryness or the need to wear a light pad in the underwear for some minor leaks during rigorous activity.  For 10-15% of men, however, urinary leakage can be much worse, requiring diapers.  For these men, a surgery can be performed to insert a device called an artificial urinary sphincter.  This device can be used to mechanically overcome leakage of urine.

3.      Dry Ejaculate:  Even for those men that regain complete erections after surgery, sex is never exactly the same.  As you may remember from my previous posts, the prostate and seminal vesicles produce most of the semen that men ejaculate when reaching an orgasm.  During surgery, the prostate and seminal vesicles are removed and the connection to the testicles is severed (like a vasectomy).  As a result, when men have an orgasm after surgery, they have a dry ejaculate.  While they still feel enjoyment from an orgasm, it feels a little different.  Because no semen is ejaculated, men are also considered infertile after prostatectomy.

4.      Bladder Neck Contracture:  About 5% of men undergoing prostatectomy develop scar tissue at the connection between the bladder and urethra tube (where the anastamosis was performed).  As a result, these men may experience difficulty emptying their bladders or leakage of urine after a period of dryness.  Fortunately, this complication can be repaired fairly easily with a minimally invasive, outpatient procedure.

While this post is not a completely exhaustive list of surgical complications after prostatectomy, I feel that it definitely provides a pretty comprehensive and objective view of all the major things that COULD go wrong during or after prostatectomy.  The purpose of this post was not to scare anyone away from surgery.  I just feel that with all of the options available to men with prostate cancer, anyone deciding on a particular treatment option needs to feel very comfortable with his choice.  This comfort, in my experience, comes with knowledge of what he is getting himself into.  In addition, for those men that proceed with prostatectomy, an understanding of potential complications can help reduce anxiety if and when these problems occur.  For other men, having enough information to identify serious complications in a timely fashion can be the key to a successful outcome.

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Saturday, April 9, 2011

Prostate Cancer and Obesity: A Deadly Combination

After I diagnose a patient with prostate cancer, we often have a lengthy discussion about treatment options and prognosis for the disease.  Many patients have a great mentality and express the desire to fight the cancer in any way possible.  Invariably, I hear a recurring question from these patients: “Doc, what can I do to increase my odds of beating this thing?”  If they are overweight or obese, I answer very emphatically, “Lose some weight.” 

Obesity is becoming an all too common phenomenon worldwide.  In the United States approximately 50% of men are considered overweight and 30% of men are considered obese.  Obesity is usually determined through a calculation of the Body Mass Index (BMI) which is weight in kilograms divided by height in meters squared.  Overweight men are classified as those with a BMI over 25 while obese men have a BMI greater than 30.  This excess weight exerts a tremendous toll on health by contributing to heart disease, diabetes, and hypertension.  Studies have demonstrated that men who are considered obese have a 50-100% higher chance of dying than men who are considered normal weight.  While we all know that obesity is a major risk factor for heart disease and some related illnesses, what does this have to do with prostate cancer?  Well, studies have also shown that men who are obese have a 40-80% higher risk of getting cancer (nonspecific) than those men that are considered to have a normal weight.  One of the cancers that has been greatly studied in the context of obesity is prostate cancer. 

While there has been no definitive proof of how obesity affects prostate cancer, numerous theories have been described.  First, studies have postulated that obesity affects prostate cancer through it impact on sex steroids within the body.  Fat in the body converts circulating testosterone to estrogen.  While testosterone is basically the “food” of prostate cancer, studies have shown that men undergoing surgery for prostate cancer have a higher risk of advanced stage cancer if there testosterone values are low. In addition, other studies have demonstrated that lower levels of blood testosterone actually correlate with a small but significant increase in the risk of prostate cancer.  All of this data seems to point to the fact that, by lowering testosterone levels in the bloodstream, excess body fat can actually predispose men to more aggressive prostate cancers.  Another theory of how fat and obesity impacts prostate cancer has to do with insulin like growth factor-1(IGF-1).  In obese men, high levels of IGF-1 are usually found in the bloodstream.  Laboratory studies have demonstrated that prostate cancer cells multiply more quickly in environments with higher levels of IGF-1.  In addition, clinical studies have shown significant correlations between IGF-1 and prostate cancer risk. 

While these theories are interesting, they do not really show us the true impact of obesity on prostate cancer.  Numerous clinical studies have evaluated the role of obesity in clinical prostate cancer.  The evidence linking obesity with the development of prostate cancer has been mixed.  While some studies have found a relationship between obesity and an increased risk of prostate cancer, others have shown no association.  Still other studies have actually demonstrated an inverse relationship, meaning that obesity was actually associated with a lower risk of developing prostate cancer.

Once prostate cancer has been diagnosed, however, there is no confusion as to the impact of obesity.  Multiple studies have demonstrated that obese men appear to have pathologically more aggressive cancer in terms of higher Gleason scores.  In addition, surgery to treat prostate cancer has been found to result in significantly higher rates of positive surgical margins in obese men.  Positive surgical margins are noted when the removed prostate gland is examined under the microscope by the pathologist after surgery.  A pathology report consistent with positive margins means that prostate cancer cells were seen at the cut edge of the removed prostate gland, meaning that the surgeon cut across some cancer when removing the prostate and that some cancer has been left behind.  Many studies have attributed this higher rate of positive margins to the fact that the body habitus of an obese man makes surgery more technically challenging.  As a result, more bleeding can occur, making visualization more difficult and positive margins more likely.  Given this theory, some have argued that robotic surgery, which enhances visualization and minimizes bleeding, should lead to better margins in obese men.  However, at least one large study, which divided patients into open versus laparoscopic surgery groups, still demonstrated a higher rate of positive margins in obese men, regardless of surgery type undertaken.

Obesity has been demonstrated to have perhaps its most significant impact on prostate cancer recurrence after surgery.  Most studies have been in agreement that obese men are substantially more likely to have a PSA recurrence (consistent with cancer recurrence) after prostatectomy as compared to those men that are of normal weight.  One large study actually demonstrated that moderately to severely obese men are 2.5- 3 times more likely to have a PSA recurrence as compared with their non-obese counterparts.  This finding is even more astounding in that it accounts for other factors that can affect cancer recurrence like preoperative PSA and Gleason score, stage, positive margins, and lymph node status.  An interesting study from Johns Hopkins published this year evaluated the effects of weight gain on men undergoing prostate cancer surgery.  The study found that men who gained approximately 5 pounds (2.2 kg to be exact) during the period of time starting 5 years prior to surgery and continuing to 1 year post surgery had twice the likelihood of  a PSA recurrence after surgery as compared to those men who maintained a steady weight.  Not surprisingly, with its impact on surgical outcomes and PSA recurrence, obesity has also been uniformly associated with an increased risk of prostate cancer mortality

I think the take home message of this post is fairly obvious.  If you have prostate cancer, probably the most important, proactive thing you can do (aside from getting treatment) is making sure to control your weight.  Find out what your BMI is from your doctor or calculate it online.  If you fall into the obese category, lose some weight.  Studies have shown that the very process of exercise can help men with prostate cancer.  A healthy, low fat diet has also demonstrated significant benefits.  Even if all of this data is wrong and you don’t benefit from escaping obesity from a prostate cancer standpoint, there is overwhelming evidence that you would benefit from the standpoint of your heart.  On that note, I want to share 1 more statistic.  The Prostate Cancer Prevention Trial followed 18,000 men for 7 years to study the impact of a drug called Finasteride on prostate cancer.  During the study, a total of 10 men died of prostate cancer.  During the same time period, 1123 men died of other causes, most of which were related to heart disease. Is that not enough of a reason to lose a little weight?

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Wednesday, April 6, 2011

Sex After Prostatectomy: Yes We Can!

One of the most dreaded complications of surgery for prostate cancer is impotence.  I have had several patients tell me that they will never consider prostatectomy because they refuse to “say goodbye” to their sex lives.  Given what they read on the internet and hear from friends, many men feel that in order to treat their prostate cancer, they need to give up on ever having sex again.  In truth, while impotence is one of the most common side effects of surgery for prostate cancer, it can be overcome.  Men facing impotence after prostatectomy have many options that will help them have a satisfying, albeit different, sex life.  The purpose of this post is to shed some light on impotence after prostatectomy and to explain the methods available to overcome it.

Studies have demonstrated that approximately half of men undergoing surgery for prostate cancer suffer from impotence after the surgery.  Men with good erections prior to surgery have a higher chance of maintaining them than those men with some level of impotence prior to surgery.  Also, older men undergoing prostatectomy appear to have a higher chance of impotence after surgery as well.  The reason why impotence is so common after surgery has to do with the nerves that are responsible for creating and maintaining erections.  These nerves are located on both sides of the prostate and are basically stuck to it.  During surgery, attempts are made to push and tease the nerves off of the prostate to preserve them (nerve sparing).  However, these nerves are often damaged in the process.  This damage is what leads to postoperative impotence.  The situation is even worse for men with aggressive disease that pushes its way outside of the prostate.  During surgery for this type of cancer, the surgeon often removes the tissue around the prostate on the side of the cancer to ensure that the prostate cancer is completely removed.  In so doing, the surgeon sacrifices the nerves on that side, often removing them completely. 

As a result of this nerve injury, most men will have some level of impotence immediately following surgery.  While we occasionally see men that have erections a few days after surgery, most will not see any erections for weeks to months.  This difference in timing has to do with the extent of damage done to the nerves, the health and vitality of the patient, and the preoperative potency.   For some men , the erections never come back naturally.  Fortunately, these men have many options from which to choose in tackling erectile dysfunction.  I divide these options into Plan A and Plan B:

Plan A

1)      Viagra and company:  The mainstay of treatment for erectile dysfunction after prostate surgery or otherwise has been a class of drugs called Phosphodiesterase 5 (PDE5) Inhibitors.  These drugs, including Viagra, Levitra, and Cialis, work by blocking the breakdown of a compound in the penis responsible for creating an erection.  For all intents and purposes, Levitra and Viagra are interchangeable, although I do have patients that swear by one or the other.  Cialis is a little different in that it lasts much longer than the other two( half life 18 versus 4 hours).  Most men with erection problems after surgery are prescribed one of these medicines after surgery to help with erections.  Of course, these medicines are not for everyone.  Men with heart disease and particularly those who take heart medicines called Nitrates can have a heart attack or even die by taking the PDE5 Inhibitors. Men with other conditions such as liver disease, low blood pressure, HIV, and many others also need to be very careful when taking these medicines.   Still others may not tolerate the side effects of the drugs.  Commons side effects reported by patients include rapid heartbeat, flushing of the face, headache, stuffy nose, visual changes, and the erection that wont go away(more on this later).  Of course, a careful discussion with a physician should always be carried out prior to taking any of these drugs.

2)      Injections:  I like to describe injectable therapy for erectile dysfunction as “turbo-charged Viagra”.  Rather than taking the medicine by mouth, you inject it directly into the base of the penis. Yes, I did say that YOU actually INSERT a NEEDLE into the side of your PENIS.  While I know this sounds very unpleasant and daunting, it is actually quite easy and tolerable.  You use a tiny needle like one you may have seen during a TB test. The whole process lasts a few seconds and the erection is usually achieved within 15-30 minutes.  From what my patients tell me, the injection does not really hurt very much, especially once they have gotten over the anxiety of doing it for the first time.  These injections tend to be more reliable than the pills and work faster.  They also seem to work despite factors, like full stomachs and stress, that often decrease the efficacy of the pills.  Like the pills, injectable medicines are also contraindicated in some men.  For example, men on blood thinning medications like Coumadin may experience bleeding during injections.  Also, the medicine can sometimes cause a decrease in blood pressure making it less than optimal for men with existing heart problems and those taking Nitrates mentioned above.  Side effects of these injections include pain or tingling in the penis, scar formation at the site of injection (leading to some curvature of the penis), a drop in blood pressure, and the erection that does not go away(more on this later).

3)      Vacuum Erection Device(VED): Those of you who watched the Austin Powers movies are probably familiar with the novelty form of this, actually, very useful tool for treating impotence.  The device is a cylinder into which the penis is placed.  Through a vacuum effect blood is brought into the penis to create an erection.  The device is then removed and the erection is maintained through a ring which is placed at the base of the penis.  When sexual intercourse is completed, the ring is removed and the erection goes away as the blood is allowed to drain from the penis.   The VED is nice in that it works for most men and, so, there are few contraindications.  Men that really should not use these devices are those with severe curvature of the penis (Peyronies Disease), those men on significant blood thinners and those with a history of the erection that wont go away(more on this later).  Most men are very happy using the pump.  The only complaints I get are that it is somewhat cumbersome to use and that it takes away some of the spontaneity of the sexual experience.  Other minor complaints include minor pain and coldness at the tip of the penis.

With any of the options of “Plan A”(less so the VED), there is a risk of a condition called priapism, which is the erection that wont go away.  I am sure that many if not most of you have seen commercials for Viagra or the other impotence drugs which end with the warning to seek medical attention if the erection does not go away in 4 hours.  The reason for this warning is that some men respond to these treatments with a painful erection that just will not go away despite having an orgasm and ejaculating.  The reason for this is that the blood gets trapped in the penis and cannot come out.  This condition needs to be treated within the first few hours because, following this window, scarring can occur in the penis preventing the ability to have any future erections.  Treatment for this condition includes draining the penis of the trapped blood, injecting medicine to counteract the effects of the erection producing drugs and, occasionally, performing surgery to bring down the erection. Men using any treatments for erectile dysfunction need to be aware of priapism and what to do in case they get it.

The 3 options mentioned above provide an excellent “Plan A” for those men that experience erectile dysfunction after prostatectomy for prostate cancer.  In my practice, over 90% of men are able to experience erections suitable for intercourse using one of the three options mentioned above.  For a small minority of men, however, “Plan A” does not work.  Those men require a little more help.  This is when we turn to “Plan B”.

Plan B

As mentioned above, some men do not respond to any of the “Plan A” strategies for impotence after prostatectomy.  Fortunately, we do have a “Plan B”.  While this strategy is certainly more invasive and risky, it is often successful when everything else has failed.  “Plan B” involves the surgical implantation of a prosthesis into the penis.  There are two types of such prostheses:

1)      Semi-Rigid Prosthesis:  This prosthesis is literally two plastic rods that are inserted into the parts of the penis that get engorged with blood during an erection.  As a result the penis is always hard.  One obvious advantage of this type of prosthesis is that it is always working, making sex potentially more spontaneous.  In addition, this prosthesis is fool-proof and does not require any particular dexterity or manipulation by the patient as may be needed with injections or the VED.  The semi-rigid prosthesis does have some risks. As with any surgery, implantation of the prosthesis has a risk of bleeding, infection, and the risks of anesthesia.  More specifically it also carries a risk of damage to the urethra, the tube in the penis which carries urine.  Long term, there is a 5% risk of the rods of the prosthesis eroding out of the skin or into the urethra tube and a 5% risk of infection of the prosthesis.  Both of these complications require surgical removal of the device.

2)      Inflatable Prosthesis: This prosthesis is much more complicated than the semi-rigid prosthesis.  The device is actually composed of three interconnected parts.  The main part of the device is comprised of two inflatable cylinders that are placed in the same location within the penis as the rods of the semi-rigid prosthesis.  These cylinders are connected to a reservoir (containing fluid) that is implanted in the abdomen and a pump that is implanted in the scrotum.  At baseline, the cylinders within the penis are deflated and, so, the penis is flaccid.  However, when the patient pushes on the pump within the scrotum (which can be manipulated through the skin), fluid from the reservoir is transferred to the cylinders in the penis which inflates them and causes an erection.  When the patient wants to deflate the cylinders, he, again, pushes the pump in the scrotum and the fluid is transferred back from the cylinders to the reservoir.  The whole process is carried out via hydraulics.  The obvious advantage of this prosthesis is that it does not require the patient to walk around with a constant erection.  There are some drawbacks, however.  First, any man that wants an inflatable prosthesis needs some level of manual dexterity that will allow him to operate the pump in the scrotum.  In addition, as with all machines, the device can and does break down, requiring the parts to be removed or replaced through further surgery.  The surgical risks are a little more extensive than those associated with a semi-rigid prosthesis because there are more surgical sites and the surgery takes longer.  The risk of erosion, however, is smaller because of the lack of the constant pressure on nearby tissue as caused by the rods of a semi-rigid prosthesis.

These prostheses can bring new life into an otherwise dead sex life of a man with impotence after prostate cancer surgery.  As mentioned, these devices usually work even when all of the mainstream approaches of “Plan A” fail.  So why not resort to these devices in the first place?  First, the surgical and device risks mentioned above make many patients wary of trying it.  Secondly, although these devices give you an erection, they do not give you a natural feeling erection.  Because no blood is flowing through the penis during an erection produced by the devices, the erection feels more artificial.  While most men who have either device implanted are happy with the fact that they can have intercourse, they often admit that sex does feel a little different.  This is why I encourage my patients to try the options from “Plan A” first, if appropriate.

As should be evident by now, treating prostate cancer does not need to be a death sentence for your sex life.  While many men undergoing prostatectomy do experience some level of erectile dysfunction, most, if not all, of them can again be sexually active.  Some of the treatments mentioned in this post are certainly more involved than others and all make sex a little less spontaneous and natural.  However, with the right attitude and approach, sex can again be possible and enjoyable for men undergoing prostate cancer surgery.

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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.

Saturday, April 2, 2011

PSA Recurrence After Prostatectomy: The Good, The Bad, and the Ugly

A major milestone in the prostate cancer journey is obtaining a PSA level after treatment.  If a man has surgery, a procedure in which the entire prostate gland is removed, the expected result is a permanently undetectable PSA.  Because a successful surgery should remove all remnants of the cancer as well as the benign elements of the prostate, there should be nothing left to produce the dreaded PSA.  Patients derive a tremendous amount of satisfaction and relief in hearing that there PSA is undetectable, an unambiguous sign that their prostate cancer is gone.  For some men, however, the news is not as great.  At some point after surgery, 15-40% of  men hear the dreaded news that their PSA is not undetectable and that, most likely, there cancer has returned.  What many patients do not know is that not all PSA recurrences are created equal.  Some types of recurrences are much more worrisome than others and require very different treatment approaches.  In this post I will try to define PSA recurrence and attempt to differentiate the different types of recurrences.

Defining a PSA recurrence seems pretty obvious at first glance.  After all, PSA after prostatectomy should be 0.  Any other number is considered a PSA recurrence. In reality, things are not that simple.  First, we have to differentiate PSA recurrence from PSA persistence.  A first PSA test obtained 1-3 months after prostatectomy should be 0.  However, any PSA value other than 0 is not considered a PSA recurrence at this time.  The reason for this is that the PSA has not recurred but, rather, has persisted. Although this difference in terminology may seem like nothing more than semantics, it makes a tremendous difference in terms of prognosis and understanding the status of the prostate cancer.  Patient who have a persistent PSA after prostatectomy almost always have metastatic disease.  While imaging tests like a bone scan or CT scan may be negative, a persistent PSA indicates that some cancer cells are lurking somewhere in the body that are simply too small to identify on imaging tests.  These cells are then labeled micrometastatic disease.  Unfortunately, patients in this situation can no longer be considered curable.  Instead, they often get palliative hormonal therapy which, fortunately, can often keep those few micrometastatic cancer cells from significantly growing for many years. These patients may also qualify for clinical trials.

Unlike PSA persistence, PSA recurrence occurs when a postoperative PSA at first goes to 0 and then begins to rise after some period of time.  However, at least technically speaking, not all rises in PSA have been considered recurrences.  Historically, a PSA rise to 0.4 after surgery has been considered a recurrence.  Rises in PSA lower than this have been considered insignificant, possible due to some left over benign prostate tissue.  More recently, the value of 0.2 has been chosen.  Although these definitions seem pretty arbitrary they actually have significance because they determine when the patient has recurrent cancer and, in turn, when they should start salvage therapy.  With the advent of ultrasensitive PSA, much lower PSA values have been recorded and some doctors have initiated salvage therapy at PSA levels significantly lower than 0.2.

As I mentioned earlier in this post, a PSA recurrence has different implications on the status of prostate cancer and subsequent prognosis depending on several factors:

1)      Time from Surgery: Many studies have demonstrated that the longer the time between surgery and PSA recurrence, the less chance that the recurrent cancer is aggressive and likely to spread.  The consensus seems to be that 3 years appears to be a critical cut off point.  One study demonstrated that for men with otherwise good risk factors, those that had a PSA recurrence more than 3 years after surgery had a 13% greater chance of surviving their prostate cancer 15 years later as compared to those men with a PSA recurrence within 3 years of surgery( 94% versus 81% survival at 15 years).

2)      Gleason Score of Prostate Cancer:  The Gleason score is a measure of how aggressive the cells of prostate cancer look under the microscope.  It generally ranges from 6-10, with higher scores being associated with more aggressive cancer.  Men with Gleason scores above 7 who have a PSA recurrence after prostatectomy are at higher risk for metastasis and death from prostate cancer.  For example, a study demonstrated that men with recurrence of a Gleason 8 or higher prostate cancer within 3 years of prostatectomy had a 19% higher chance of surviving their prostate cancer within 15 years than those men with a recurrence of Gleason 6 or 7 prostate cancer within 3 years of prostatectomy( 62% versus 81% survival at 15 years).

3)      PSA Doubling Time: The PSA doubling time appears pretty self explanatory.  The term refers to the time it takes for the PSA to double in value.  To calculate this number you need a few PSA values spread at least 3 months apart.  You also need to use a fairly complex formula to get the exact value.  For our purposes, a rough, eyeball assessment will do just fine.  For example, by looking at a series of PSA values we can roughly estimate if the PSA is doubling every month, every 6 months, or every year, etc... Studies have demonstrated that PSA doubling time is one of the most important prognostic factors used to evaluate a PSA recurrence after prostatectomy.  Let’s look at an example:  If a man has a PSA recurrence more than 3 years after prostatectomy for a Gleason 6 prostate cancer and his PSA doubling time is more than 15 months, his chance of surviving the prostate cancer at 15 years is 94%.  If that exact same man has a PSA doubling time of less than 3 months, however, his chance of surviving prostate cancer at 15 years is only 19%.  As you can see, the importance of the PSA doubling time cannot be overstated.

These 3 factors are vital in evaluating a man with a PSA recurrence after prostatectomy not only to determine prognosis but, also, to figure out what future treatment needs to be undertaken, if any.  A man with a PSA recurrence more than 3 years after prostatectomy for a Gleason 6-7 prostate cancer and a PSA doubling time of greater than 15 months has a 94% chance of surviving his prostate cancer at 15 years.  In contrast, a man with a PSA recurrence less than or equal to 3 years after prostatectomy for a Gleason 8-10 prostate cancer and a doubling time of less than 3 months have <1 % chance of surviving for that same period of time.  As you can imagine, most men find their situation somewhere in between these two extreme scenarios. 

Men with favorable factors most likely have a local recurrence of the cancer in the part of the pelvis where the prostate was located.  This type of recurrence tends to move more slowly and can be cured with radiation therapy with some success.  Some men, depending on their overall health and age, may not even need any treatment for this type of low risk recurrence.  Men with high risk factors, in contrast, most likely have metastatic disease.  This type of recurrence is usually more aggressive and not responsive to local therapy.  Instead, men with this type of PSA recurrence are usually treated with palliative hormonal therapy to try to control rather than cure the recurrent cancer.  Others may opt for clinical trials to try novel treatments to battle the more aggressive cancer.

The take home message of this post is to NOT treat all PSA recurrences the same.  While a PSA recurrence is obviously disappointing and frightening it is not always as bad as you might think.  Many recurrences are very manageable and still offer the possibility of cure. Some recurrences may not even need to be treated.   Men with PSA recurrence should discuss their specific risk factors with their urologist in determining an appropriate treatment course. 

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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.