Showing posts with label Radiation Therapy. Show all posts
Showing posts with label Radiation Therapy. Show all posts

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.

Urination

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

Friday, May 6, 2011

Combining Hormonal Therapy With Radiation To Treat Prostate Cancer: Who Needs It And For How Long?

A question that I have repeatedly heard from readers has been about the length of time hormonal therapy needs to be given in conjunction with radiation to treat prostate cancer.  As I replied to these readers, the answer, like most aspects of prostate cancer treatment, is not very straightforward and remains somewhat controversial.  In this post I will attempt to clarify which men actually need hormonal therapy in addition to radiation, the benefits of this additional hormonal therapy, and the ideal duration of the therapy.

Why Add Hormones to Radiation Therapy?

The benefits of adding hormones to radiation therapy for prostate cancer were first demonstrated through animal experiments.  These studies evaluated the added efficacy of androgen deprivation (hormonal therapy) when combined with radiation therapy in treating prostate tumors in mice.  The studies scientifically demonstrated that the hormonal therapy reduced the amount of radiation necessary to destroy and control the growth of the tumors.  These and other studies have proposed that radiation and hormonal therapy work synergistically to destroy prostate cancer cells and keep them from spreading locally and into the bloodstream. 

The added benefits of hormonal therapy were then tested in the clinical setting on real patients.  One of the seminal studies testing the theory was conducted in Europe over a decade ago. The study compared the outcomes of men with locally advanced prostate cancer who underwent either radiation therapy alone or radiation therapy combined with a 36 month course of hormonal therapy.  The study demonstrated that, 10 years after treatment,  men undergoing combination therapy enjoyed superior overall survival (58% vs 39%) and a much lower chance of dying specifically from prostate cancer ( 11% vs 31%) when compared with those men undergoing radiation alone.  Studies such as this ushered in the wave of hormonal therapy that has been becoming more and more popular in the treatment of localized prostate cancer.     

As more and more patients were placed on hormonal therapy, it soon became apparent that this additional treatment does not represent a free lunch.  As I described in my previous post, hormonal therapy comes with significant risks to your heart while increasing your chance of developing diabetes.  In addition, hot flashes and sexual dysfunction can have a dramatic impact on quality of life for men on the therapy.  As such, many began to wonder if 3 years of hormonal therapy is really worth the benefits.  Studies have been conducted comparing the combination of radiation plus short term hormonal therapy (4-6 months) with radiation alone.  One such study demonstrated a superior 8 year overall survival for men undergoing the combination therapy (74% vs 61%) as compared to men undergoing radiation therapy alone.  The presence of this new data subsequently begged the question of whether long term hormonal therapy yielded any benefits above and beyond those achieved with short term hormonal therapy.  Excellent, randomized studies were conducted to answer just this question. 

Optimal Duration of Hormonal Therapy

Two large, randomized trials have been carried out comparing short term with long term hormonal therapy in combination with radiation therapy.  These studies were carried out specifically in men with HIGH RISK prostate cancer.  Only men with either locally advanced prostate cancer (T2c-T4) or positive lymph nodes were evaluated.  I emphasize this point because, as I shall explain later, the results and conclusions can not and should not be applied to treatment decisions for ALL men with prostate cancer. 

The first trial, known as Radiation Therapy Oncology Group 92-02 studied over 1500 men with T2c-T4 prostate cancer (cancer which took over both lobes of the prostate and/or extended out of the prostate to varying extents) with or without positive lymph nodes.  Men in the study were randomly enrolled into one of two treatment protocols:
1)      Radiation plus 4 months of hormonal therapy (starting 2 months prior to radiation)
2)      Radiation plus 28 months of hormonal therapy(starting 2 months prior to radiation)

The study demonstrated that, after 10 years, men undergoing long term hormonal  therapy enjoyed better cancer specific survival (89% vs 84%), lower chance of metastatic disease (15% vs 29%), and a lower chance of further local spread ( 12% vs 22%) than those undergoing short term hormonal therapy .  What the study did not demonstrate, however, was a significantly improved overall survival rate for men undergoing the long term versus the short term hormonal therapy.  The study then analyzed a particularly high risk subset of men with Gleason 8-10 prostate cancer.  In this subset of patients, in contrast, a significantly superior overall survival rate (45% vs 32%) was seen in men undergoing long term hormonal therapy.

The second study was conducted by the European Organization for Research and Treatment of Cancer.  This trial evaluated 970 men with either locally advanced prostate cancer (T2c to T4) or men with positive lymph nodes and any local stage.  The study divided the patients randomly into two treatment groups:
1)      Radiation therapy plus 6 months of hormonal therapy (starting the first day of radiation).
2)      Radiation therapy plus 36 months of hormonal therapy (starting the first day of radiation).

After about 6 years of follow up, the study demonstrated a small but significant overall survival advantage for men on long term versus short term hormonal therapy (85% vs 81%).  The difference in death rates (19% vs 15%) represented a 42% higher chance of death for men undergoing short term versus long term hormonal therapy. 

While demonstrating slightly different impacts, both studies concluded that men with HIGH RISK prostate cancer should be considered for long term hormonal therapy.


Long Term Hormonal Therapy: Who Really Needs It?
While the above mentioned studies argue for adding long term hormonal therapy to radiation for treatment of HIGH RISK prostate cancer, they DO NOT conclude that all men undergoing radiation therapy for prostate cancer need hormonal therapy.  Before discussing the suggested regimens for men without high risk disease, we should review the accepted “risk” categories for prostate cancer:

1)      High Risk: Prostate cancer that is locally advanced (T2C-T4) and/or Gleason score 8-10 and/or associated with a PSA greater than 20
2)      Intermediate Risk: Prostate cancer with moderate local stage (T2b) and/or Gleason score 7 and/or PSA 10-20.
3)      Low Risk: Prostate cancer with low local stage (T1b-T2a) and Gleason score 2-6 and PSA less than 10.

These risk categories are very important to understand, particularly in context of prostate cancer studies.  In relation to adding hormonal therapy to radiation for prostate cancer, the utility of the additional hormonal therapy depends on what risk group you are looking at.  As I mentioned above, the added benefits of hormonal therapy, particularly long term hormonal therapy were demonstrated only in HIGH RISK prostate cancer patients.  In contrast, no study has ever demonstrated any benefit of adding hormonal therapy to radiation of LOW RISK prostate cancer.  The data for INTERMEDIATE RISK is more mixed.  While no studies have specifically evaluated the added benefit of combining hormonal therapy with radiation therapy for INTERMEDIATE RISK prostate cancer, numerous patients with INTERMEDIATE RISK disease were included in the studies evaluating HIGH RISK patients.  These studies did demonstrate a benefit of adding hormonal therapy to a radiation therapy regimen for patients with INTERMEDIATE RISK disease.  No study, however, has demonstrated any significant additional benefit of long term over short term hormonal therapy for INTERMEDIATE RISK disease.  As a result, many of the radiation oncologists performing these studies recommend a combination of short term hormonal therapy and radiation for men with INTERMEDIATE RISK prostate cancer.  This recommendation, of course, is only valid  if the risks of the additional hormonal therapy (heart risk, diabetes, osteoporosis) do not outweigh the benefits for a given patient.  In addition, because no randomized studies have been carried out looking to answer this question in men with INTERMEDIATE RISK disease, the data and recommendations I have just mentioned for INTERMEDIATE RISK disease can be considered fairly trustworthy but not definitive.

Take Home Message

The controversy over the optimal duration of hormonal therapy to give in combination with radiation for prostate cancer again demonstrates the recurrent theme we hear about repeatedly in relation to prostate cancer therapy: prostate cancer treatment cannot be carried out with a “one size fits all” approach.  While studies seem to demonstrate a modest although significant advantage to long term ( > 2 years) hormonal therapy in addition to radiation for HIGH RISK prostate cancer, there has been NO evidence demonstrating that hormonal therapy for LOW RISK prostate cancer is of any benefit at all.  INTERMEDIATE RISK prostate cancer, in turn, may be optimally managed with a combination of radiation and short term hormonal therapy although we still await definitive studies to confirm this.  In addition, even when keeping these risk groups in mind, the final decision of whether or not to add hormonal therapy to radiation (and, if so, for how long ) really rests on weighing the risks and benefits for each individual patient. In some men with HIGH RISK prostate cancer, cardiac and metabolic risk factors may make the risks of heart attack and diabetes posed by hormonal therapy far outweigh the benefits of the treatment.  In contrast, some otherwise healthy men with HIGH RISK prostate cancer may derive significant benefits from the additional hormone therapy with minimal additional risks.  The key to answering this question is to really understand your situation.  Make sure that you understand your particular prostate cancer risk group.  Also, make sure that you discuss your cardiac and metabolic risk factors with both your urologist/radiation oncologist and your primary doctor (who is more familiar with your overall health).  Finally, make sure that your doctor weighs these competing factors with you so that you can be assured that, no matter what your given situation, the treatment course you chose truly provides you with more benefits than risks.


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