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The Treatment of Localized Disease

Last Revised October 10, 1997
[Procedures May Have Changed]

Introduction | Warning to patients | "Watchful waiting" | Pelvic lymphadenectomy |
Radical surgery | External beam radiation therapy | Brachytherapy | Cryosurgery |
Neoadjuvant and adjuvant hormonal therapy | Post-surgical radiation therapy


Localized prostate cancer is cancer confined to the prostate, but can include situations in which the cancer invades into -- but not through -- the prostate capsule, which defines the border of the prostate. As discussed in the section on clinical staging, such cancers are known as stage T1 or stage T2. Localized prostate cancer is potentially curable in a very high proportion of patients, which means that, at least in theory, all of the prostate cancer cells can be removed or killed, with the result that the patient does not go on to have recurrent prostate cancer.

The key problems with the management of localized prostate cancer are twofold. First, prostate cancer which appears to be localized according to all of the tests carried out prior to surgery may, in fact, not be localized at all (see the section on misstaging). Second, even though the cancer is confined to the prostate, it may not be possible to either remove or otherwise destroy all of the cancer cells because of surgical or other treatment problems.

There are three basic types of management currently considered to be standard options for the care of patients with localized prostate cancer: (a) so-called "watchful waiting," (b) radical surgery to remove the prostate, and (c) various forms of external beam radiotherapy to kill the prostate cancer cells. In addition there is a range of experimental options currently under investigation, including cryosurgery, brachytherapy (radioactive seed implantation), and the use of "adjuvant" or "neoadjuvant" hormone therapies in combination with surgery or radiation. In this section, we will discuss all of these subjects in some detail.

Warning to patients

Patients are warned that ALL treatments for prostate cancer are controversial to a greater or lesser degree. There are few if any areas of complete agreement within the medical community about the appropriate treatment of any particular stage of prostate cancer. For this reason, patients are strongly advised to seek as much advice and knowledge as they can reasonably manage to obtain prior to making decisions about their treatment. In particular, patients should be aware that all treatments currently available and carried out with the intent to cure localized prostate cancer have been associated with high probabilities of failure and/or significant adverse effects on quality of life.

"Watchful waiting"

Are there people who don't need treatment?

Physicians have always known that it is probably better not to attempt to treat some patients with localized prostate cancer. These patients just wouldn't be able to deal with the rigors of the types of treatment available. However, there has been much controversy about this topic in the recent past -- largely related to exactly which patients are not appropriate for definitive treatment with radical surgery or radiation therapy. This is just one of the many controversies about the proper management of prostate cancer, and it exemplifies why it is so important that patients try to understand as much as they can about how their disease can be managed and the potential benefits and risks attached to each type of management.

Case example 1: Chuck P. is 82 years old and long retired. He has been having regular medical care for the past 16 years. He has adult onset diabetes, high blood pressure, and considerable difficulty with his breathing. Despite everyone's advice, he is still smoking 10 or more cigarettes a day. Many days he is unable to do much more than sit in the chair in the living room while his wife, Alice, runs the house with some help from their daughter and grandchildren, at least one of whom tries to come by every day. This year, during Chuck's most recent visit to his doctor, the doctor thought he could feel a very slight abnormality in Chuck's prostate when he carried out a DRE. Chuck asked the doctor to explain what this could mean. The doctor told Chuck that prostate cancer was one of several possibilities and said he wanted Chuck to have a PSA test. Chuck had never had this test before. When the result came back, the doctor told Chuck his PSA was 12.8 ng/ml, and they needed to talk about what to do.

Now Chuck is almost certainly a prime candidate for watchful waiting. He is not a young man, and he already has significant health problems. The chances are that his prostate cancer is localized, and it could be years before it progresses to the point at which Chuck develops clinical symptoms of prostate cancer. If he has prostate cancer confirmed by a biopsy, then he has to consider whether the likely side effects of surgery or some other form of therapy will be worse for his quality of life than not having any therapy at all until his disease progresses. In truth, Chuck may not live long enough to ever develop symptoms of prostate cancer. Should he really put himself through the risks of surgery or another form of therapy? Chuck's doctor might well recommend that, rather than consider treatment, he would prefer to monitor Chuck's prostate on a regular basis (say every 6 months) with a DRE and PSA tests. If there is no significant change in Chuck's PSA or his DRE, then there may be no need to treat Chuck ever.

Of course, there are also other situations.

Case example 2: Andy J. is a 55-year-old business executive. He is fit and active. With a single exception his family has a history of living well into their 80s. The exception is his uncle (one of his mother's younger brothers) who died from prostate cancer at the age of 62, just 12 years ago. Andy has been having regular DREs and PSA tests since he turned 50. The PSA was almost undetectable until last year, when it was 3.7 ng/ml. This year his doctor tells him that his PSA is significantly elevated: 11.4 ng/ml. There is no other sign of cancer.

Assuming Andy has prostate cancer, chances are he is going to want (and should have) treatment. There is a family history of prostate cancer. However, Andy otherwise has a good chance of more than 20 years of life ahead of him. His PSA value has risen significantly over a short period of time. A sextant biopsy under ultrasound guidance is probably essential, and further tests should probably be carried out to attempt to ensure that the cancer -- if it is cancer -- is confined to the prostate. Few physicians would consider watchful waiting for Andy.

Now there are going to be patients who are more obvious candidates for watchful waiting than Chuck P. There will be also be patients who need treatment even more certainly than Andy J. However, there are also going to be thousands of people who are somewhere between Chuck and Andy. How much younger and healthier would Chuck need to be before he became a clear candidate for definitive treatment? How much older should Andy be before watchful waiting becomes a reasonable option, assuming he remains fit and active: 69 years old? 74 years old? 79 years old? Physicians and their patients are faced with questions like this every day -- and there are no absolute answers.

So what is the controversy?

The controversy is based on divisions of opinion between groups of physicians about several different sets of data.

In the first place, there are data from Europe (in particular from Denmark) which suggest that for a very high proportion of patients the benefit of surgery is, at best, very small. In other words, at least at a first look, these data appear to indicate that there is little or no survival benefit from practicing definitive treatment with curative intent for localized disease. However, these data are easy to criticize on a variety of levels. Indeed, when they were published in the Journal of the American Medical Association, they caused uproar among American urologists because it was felt that the data had been inappropriately analyzed. It is certainly the case that there were limitations to the studies published by the Danish investigators. However, they may have done everyone a favor by making urologists think harder about which of their patients with localized prostate cancer really did need definitive treatment.

In the second place, a group of American physicians have been suggesting for some time that treatment of patients with localized disease offers only marginal benefit over watchful waiting. (They referred to watchful waiting as "conservative management.") The data used by this group of physicians to support their conclusions were analyzed using a relatively sophisticated mathematical procedure known as Markov modeling. Unfortunately, Markov modeling is not completely objective. It requires researchers to make a number of assumptions in order to create and structure any particular model. When other groups of physicians reanalyzed these same data while making slightly different assumptions, they showed a significant benefit in favor of radical surgery as compared to watchful waiting.

A major clinical trial (the so-called PIVOT trial) has been organized in order to attempt to resolve this controversy. (PIVOT stands for Prostate cancer Intervention Versus Observation Trial.) In this trial, patients are randomized to receive conservative management ("watchful waiting") or curative surgical treatment. However, some physicians believe that there are inherent problems with this trial. It may well be that even when the PIVOT trial is completed, and the results are carefully analyzed, we still will not know, with any degree of certainty, whether watchful waiting is any better than radical surgery when it comes to the treatment of any particular patient with localized disease.

What is involved in watchful waiting?

Very simply, watchful waiting or active surveillance is a carefully planned set of actions designed to monitor the perceived progress of any signs of prostate cancer in a patient who either has prostate cancer confirmed by a biopsy or who has signs of prostate cancer (e.g., an elevated PSA level or biopsy proven, high-grade PIN) but has chosen not to have a biopsy.

At the simplest level, active surveillance would comprise regular check-ups at which the physician would carefully seek signs indicating increasing progress of prostate cancer (e.g., further increases in PSA level or increasing hardness or irregularity of the prostate on DRE). Such regular check-ups might be carried out every 3 or 6 months, depending upon the views of the individual physician and the comfort level of the individual patient. Should there be clear signs of rapid progression of the cancer, there is always the opportunity to take therapeutic action as appropriate.

Risk/benefit analysis

If, after a diagnosis of localized prostate cancer, you have to decide whether watchful waiting or definitive treatment is the best option for you, you need to consider a range of questions and discuss them carefully with your doctor(s):

  • How old are you and how long do you expect to live?
  • What is your present quality of life?
  • Have you carefully considered the risks associated with surgery or other forms of treatment?
  • How will you react if you are one of the relatively rare patients who have long-term incontinence after surgery?
  • How frequently do you really have intercourse now, and with what degree of satisfaction for all concerned?
  • How well will you deal with impotence (or some form of device for the alleviation of impotence) if you cannot receive treatment which is guaranteed to avoid this side effect?
  • Can you deal with the possibility that if you don't have treatment you may be living with cancer for years?

The true "benefit" of watchful waiting is that you do not have to take any of the risks associated with treatment. The true risk is that you could be unlucky. You could have a form of prostate cancer that progresses quickly and, by the time you and your doctor discover this, the cancer has escaped the prostate and is therefore incurable. No one can tell you the degree of risk in your particular case. All you can do is discuss your particular symptoms and test values with your doctor and try to come to a decision with which you both feel comfortable.

There is, however, one thing worth remembering. You don't have to make your decision in a hurry. Prostate cancer is a very slowly growing disease. A couple of weeks or even a couple of months is not likely to have any effect on the stage of the disease. Make a decision when you are ready. Talk to your wife or significant other about it. Learn everything you can before you take an irrevocable step. For some patients treatment is absolutely the right step; for others it may be something they simply didn't need to do.

Pelvic lymphadenectomy

[Reminder: this document was last revised in 1997. Procedures may have changed.]

Pelvic lymphadenectomy is frequently carried out prior to further definitive treatment for localized prostate cancer. It means the removal of the pelvic lymph glands, which can then be quickly examined by the pathologist to see whether there is cancer in these glands. The presence of prostate cancer in the pelvic lymph nodes is a sure sign that the cancer is no longer localized. In this case there is very little point in carrying out any form of treatment which is designed for the management of localized prostate cancer.

Pelvic lymphadenectomy can be carried out using one of two basic methods:

  • There is the option of a separate procedure to remove the pelvic lymph nodes, which might precede any decision about either radical surgery or radiation therapy, in which case the method which is most likely to be used will be "laparoscopic lymphadenectomy," a technique which avoids a major surgical incision.
  • On the other hand, as the first step in a radical retropubic prostatectomy, the surgeon will often resect the pelvic lymph nodes and ask the pathologist for a "frozen section."
In either case, if the lymph nodes are found to be positive, it would be relatively unusual to decide to proceed with radical surgery. External beam radiation may, however, be carried out following a discovery of positive pelvic lymph nodes, since it is possible to include the area of the lymph nodes in the radiation field. The patient needs to understand that, in such a case, we are no longer dealing with treatment of localized prostate cancer: this is locally advanced or possibly advanced prostate cancer.

Radical surgery

[Reminder: this document was last revised in 1997. Procedures may have changed.]

General overview

The simple objective of radical surgery for the treatment of localized prostate cancer is the surgical removal of all tissue which might be expected to include prostate cancer cells, followed by appropriate reconstruction of the genitourinary system in order to allow normal urination and intercourse if possible.

Unfortunately, on the one hand, removal of the prostate and other associated tissues is not a simple operation. It can be complicated by a whole variety of minor and major problems. It is a highly invasive procedure requiring deep general anesthesia. In the very worst case scenario, a very small percentage of radical prostatectomy patients (now probably less than 1 in 100) die each year during or as a direct consequence of their surgery. On the other hand, modern surgical techniques and procedures, and significant improvements in the skills of urological surgeons over the past few decades, have clearly lowered the risks associated with prostate cancer surgery. Indeed, many surgeons are now comfortable carrying out such surgery and sending patients home within a matter of 3 or 4 days -- sometimes even less.

Careful reviews of large series of prostate cancer patients receiving surgery at selected centers have now demonstrated relatively high rates of disease-free survival in patients with organ-confined (localized) disease for many years with relatively low levels of side effects. However, many questions still remain, and some of them may never be properly answered. In the section on watchful waiting, we have seen that there is controversy over the relative merits of watchful waiting compared to surgery. Here are a few examples of other questions which have controversial aspects:

  • Is radical surgery better than, worse than, or equal to external beam radiation therapy as a form of treatment for localized prostate cancer?
  • What forms of prostate surgery are most appropriate for which men?
  • Which patients should be receiving so-called "nerve-sparing" prostatectomies?
  • What is a "good" incidence of side effects following radical prostate surgery?
  • What is the big disagreement between Dr Stamey and Dr Walsh all about?
This section will attempt to handle as many of these issues as possible. However, you should remember, as always, that the information here is not about you as an individual, it is about general principles. You will have to discuss your individual case in detail with a doctor who you trust and respect.

It may be helpful for many newly diagnosed patients to learn from the personal experience of others. [For a more updated version, see Ron Voss's excellent account as part of his "Handbook."]

The types of surgical intervention

Once the decision has been made to remove the prostate, there are two basic methods of prostate surgery: radical retropubic prostatectomy and radical perineal prostatectomy. These names refer to the route which the surgeon takes in order to be able to remove the organ. Regardless of the surgical method, there are also a number of options which may be considered by the surgeon. The surgeon can talk to you about these options before the operation. However, it is likely that he or she cannot make final decisions about how to act until the operation is in progress. The options include

  • Nerve sparing in order to attempt to retain potency
  • Wide dissection, including cutting through of the neurovascular bundles, in order to attempt to ensure removal of all the cancer
  • Stopping the operation because it is clear that the cancer has escaped from the prostate.
Radical retropubic prostatectomy

In this procedure, the surgeon cuts down through the abdomen in order to expose the patient's prostate. In a complex set of procedures, the surgeon then cuts out as much of the prostate as he or she possibly can. Ideally, the entire prostate is removed together with the seminal vesicles. After removal of the prostate and the seminal vesicles, the urethra is carefully rejoined to the "neck" of the bladder so that on recovery the patient will be able to urinate in a normal fashion after a relatively short period of time (usually a few weeks or months).

This is a extremely simplified description of radical retropubic prostatectomy.

Radical perineal prostatectomy

In this procedure, the surgeon cuts up through the perineum in order to expose the patient's prostate. While the different surgical route requires significant technical differences in the manner in which the operation is carried out, the surgical principles are pretty much the same as for a radical retropubic prostatectomy.

What is a "nerve-sparing" prostatectomy?

[Reminder: this document was last revised in 1997. Procedures may have changed.]

Until only a few years ago, surgeons considered that any form of prostatectomy was inevitably associated with subsequent impotence in all but the most unusual (and normally unexpected) circumstances. Then, in the early 1980s, Dr Patrick Walsh developed what he describes as a new "anatomical" retropubic approach to radical prostatectomy.

Using this careful, anatomical approach in carefully selected patients with localized disease, Dr Walsh demonstrated that it was possible to leave intact one or both of the two "neurovascular bundles" which pass close to the prostate capsule. In almost all men, these neurovascular bundles are essential to the ability to have and maintain an erection sufficient for normal intercourse. Thus, by being able to leave these nerves intact, Dr Walsh was able to remove the patient's prostate while allowing him to recover his potency following recovery from the surgery.

Dr Walsh and his co-author, Janet Farrar Worthington, have offered a detailed discussion of the details of this surgery in their book The Prostate: A Guide for Men and the Women Who Love Them. In addition, this technique is described on the Web in the materials offered by the Brady Urological Institute of Johns Hopkins. If you want to obtain the details of this operation, The Prostate Cancer InfoLink believes that it is most appropriate for you to read about this in Dr Walsh's own words. However, we wish to emphasize two points which Dr Walsh and Ms. Worthington are very careful to make in their book.

First, "There is no way for the surgeon to know for certain beforehand whether or not the [neurovascular] bundles can be spared." In other words, it is only after the surgeon has a clear view of the prostate and the actual operative situation, that he or she can make the final decision whether these nerves can in fact be spared. Thus, if you want to seek a "nerve-sparing" prostatectomy, you must understand up front that your surgeon may have to tell you immediately after the operation that such nerve sparing was simply not possible for one or more reasons. There is absolutely no way that any surgeon can guarantee to you, before surgery, that he or she can give you a nerve-sparing radical prostatectomy which will remove all of the cancer. If any physician makes such a guarantee to you, The Prostate Cancer InfoLink strongly recommends that you seek a second opinion immediately.

Second (and here we are using the authors' own italics), you must "Think about what is really important! The primary goal here isn't to preserve potency, but to get rid of the cancer in a careful but thorough way." In other words, if your surgeon can preserve your potency but still leaves you with cancer cells in the area of your prostate, that was NOT a curative operation, so what was the point? If you have decided to have surgery, then you need to be certain that the surgeon will make every attempt to remove all the cancer from your prostate if he or she possibly can.

Many urologists have learned how to carry out the procedure originally developed by Dr Walsh. Some of those urologists -- including Dr Thomas Stamey -- have made modifications to the procedure. However, the general principles of the operation remain the same. Indeed the very best urological surgeons who specialize in management of prostate cancer have probably each carried out hundreds of "nerve-sparing" prostatectomies since this operation was introduced and generally accepted.

As a curative surgical technique, nerve sparing prostatectomy, which is the term most people now use to describe the various forms of Dr Walsh's original procedure, is strictly limited to patients with localized prostate cancer. While it would be theoretically possible to spare the neurovascular bundles in surgical treatment of some forms of non-localized prostate cancer (a "debulking" procedure), it must be remembered that since the cancer is no longer localized, the prostatectomy is not being carried out with curative intent. If it is not being carried out with curative intent, it is worth asking why it is being carried out at all.

The complications of surgery

There is a general belief that the complications of surgery may be highly dependent upon the skills of the surgeon selected by the patient. If this is true, then it suggests that the patient has some degree of control over the potential for post-surgical complications if he chooses a highly experienced surgeon. However, there is at this time no well-documented and objective evidence to confirm that complication rates are lower in patients treated by more experienced surgeons.

Radical prostatectomy is potentially more difficult in a patient who has had a prior transurethral resection of the prostate (TURP). It should be recognized that the available information on complications for any type of treatment for prostate cancer always reflects the accumulated data of prior years. Thus, since it is generally recognized that treatment for prostate cancer has gradually improved, it is also probably true that complication rates today are at least fractionally lower than the published complication rates.

Having said that, the complications following radical prostatectomy can include short and long-term urinary incontinence, urethral stricture (blockage of the urethra which results in difficulty in urinating), impotence, and the general problems associated with deep anesthesia and highly invasive surgery. According to a study published in 1993, the number of patients dying within 30 days of a radical prostatectomy was 2 in every 100 patients. However, the urology community currently argues that this has been significantly reduced in the past three or four years. There is no doubt about the fact that morbidity and mortality rates increase with age, and that they are appreciably higher in men over 75 years of age than they are in younger surgical candidates.

There is extensive discussion regarding the incidence of post-surgical incontinence. Individual series from major surgical centers have reported long-term incontinence in only 6% of patients. However, the question, "What is incontinence in a post-surgical 65-year-old," has never been satisfactorily answered. Occasional stress-related urinary dribbling could be occurring in an unknown but high proportion of patients who state that they are "continent." This can certainly be substantiated by case reports in the patient literature. Patients should be aware that short-term incontinence for several weeks or months after surgery is close to certain. Equally, serious long-term incontinence is well documented in a small but significant number of individuals. In a 1993 survey of Medicare patients who received radical prostatectomies between 1988 and 1990, over 30% of the patients reported that they were using pads or other methods for management of incontinence, and over 60% of the patients claimed that urinary wetness was (at least occasionally) still a problem for them. Other studies seem to suggest that at this time there are no significant differences in rates of urinary incontinence between the patients who receive a nerve-sparing operation as compared to those who receive standard forms of radical prostatectomy.

According to at least one report from a major academic center, radical prostatectomy is probably responsible for at least some loss of sexual function and potency in all patients. In other words, even if you have a successful nerve-sparing operation, you should not count on having the same level of potency after the operation as you had before. It appears to be generally agreed that in case series from major prostate surgery centers the percentage of patients who recover sufficient potency for satisfactory sexual intercourse is between 40% and 65%. However, 60% of the Medicare patients in the study mentioned earlier reported no erections since surgery, and 90% said that they hadn't had an erection sufficient for intercourse in the month preceding the surgery. A report on the perceived quality of life of men treated for localized prostate cancer in a managed care setting has suggested that complications as a result of surgery are common. However, this study encompassed men diagnosed with prostate cancer between 1961 and 1991; one could reasonably ask whether its findings are entirely relevant for men diagnosed today.

How should you choose between surgery and radiation therapy?

[Reminder: this document was last revised in 1997. Procedures may have changed.]

A widely respected urologist based in Norfolk, Virginia, Dr Paul Schellhammer, is a regular speaker on the comparative values of radiotherapy and surgery for the treatment of localized prostate cancer. Dr Schellhammer often shows a slide which describes how often he and his colleagues recommended surgery or radiation therapy over the past 20-odd years. This slide shows a series of "humps" which correspond to more recommendations for surgery or for radiation therapy in any particular time period.

Dr Schellhammer's point is that we don't know -- in general -- whether radiotherapy or surgery is the better choice for localized prostate cancer. Surgical techniques and equipment improve in one year, and then the next year there are improvements in the techniques and equipment of radiotherapy. Dr Schellhammer sometimes suggests that there are "fashions" over time in the treatment of prostate cancer. Like all fashions, they are the result of uncertainty as to what is the best thing to do. Maybe in time we will be able to characterize absolutely which patients are the right candidates for radiotherapy and which are right for surgery. However, even then, every single patient will be an individual case and must be considered as such.

On several occasions, attempts have been made to carry out trials which randomized patients to surgery or radical prostatectomy to try to resolve the question as to which is the more effective modality. With a single exception in the 1970s (which has been much debated ever since), none of these trials have ever succeeded in enrolling enough patients to get any meaningful results. In the first place, the radiotherapy and the urology communities have been resistant to enrolling patients into such trials. In the second place, patients have also been resistant because they want to feel that they have some input into what is (perhaps not surprisingly) considered to be an important decision. It would be wonderful if this issue could, finally, be resolved. However, The Prostate Cancer InfoLink is doubtful that the necessary trial can ever be appropriately carried out.

Now there are certain situations in which there is sufficient information to offer relatively uncluttered guidance to the patient and his doctor. Here are some examples:

  • According to the National Cancer Institute, external beam radiation therapy is not recommended for patients whose PSA is higher than 15 ng/ml.
  • External beam radiation therapy is not capable of substituting for nerve-sparing radical prostatectomy. In other words, if you and your doctor absolutely decide that curative therapy is appropriate and that it is possible and personally essential to try to keep your sexual potency for you, then external beam radiation therapy is not an option because it is associated with significant levels of impotence in the long term.
  • The earlier and lower the stage and grade of your localized prostate cancer, the more likely it is that surgery is a superior option for you. This is because radiation therapy is still inaccurate -- even using the very latest techniques. Surgery, when properly conducted in appropriate patients, has a chance of resulting in removal of all cancer tissue without major long-term adverse effects.
  • The later and higher the stage and grade of your localized prostate cancer, the greater is the risk that it is not really localized at all, in which case surgery simply will not work as a curative therapy although radiotherapy might.
The increasing use of neoadjuvant and adjuvant hormonal therapy in the treatment of patients with stage T2 prostate cancer may make it even harder to choose appropriately between surgery and radiotherapy until some of the current clinical trials have been completed and published. This could take years. So what is a patient to do?

The most practical suggestion which we can offer is that whenever possible a patient with a preliminary diagnosis of localized disease which can be treated with the intent of curing the patient should try to obtain several opinions before trying to come to any conclusions. Those opinions should, in an ideal world, probably include the views of your primary care physician, at least one or two urologists, and at least one radiation oncologist. Of course it should be added that, if you accumulate these three (or more) opinions, you may find you are wiser but that making the choice has become more difficult. We didn't say any of this was easy!

Seeking and obtaining a second opinion is commonplace among patients diagnosed with prostate cancer, and is generally accepted by the medical insurance community. Often one physician will be helpful in enabling you to secure an appropriate second opinion. It is always useful, if you can manage it, to obtain at least one opinion from a physician who will have no financial interest in your subsequent treatment.

When you talk to your physicians, listen to them with all the attention you can muster. For your own sake, ask them questions if you aren't absolutely positive about what they are recommending and why. The important thing is to make the best decision you can with all the confidence you can pull together. Believing in the decisions you make with your doctors is a very important aspect of the overall management of any cancer.

What is the big disagreement between Dr Stamey and Dr Walsh all about?

Some time ago (September 1994) an academic disagreement between Dr Thomas Stamey of Stanford University and Dr Patrick Walsh of Johns Hopkins University became public as the result of an article written by Dr Stamey and a letter which Dr Walsh wrote to one of his patients in response to selected comments in the Stamey article. The original Stamey article and Walsh's response are accessible on the World Wide Web. This academic disagreement had been widely known for several years within the urology community. [The original links to the letters no longer work. However, the material is preserved at Don Cooley's site.]

It is probably not possible on the basis of the available data to resolve the distinctions between the point of view expressed by Dr Stamey and the point of view expressed by Dr Walsh. These two surgeons have, over the past 15 to 20 years, both made outstanding contributions to knowledge about prostate cancer. In 1995, Dr Stamey received the highest award of the American Urological Association for his lifetime contributions to urology. It is almost a foregone conclusion that Dr Walsh will receive the same award at some time in the future. The fact of the matter is that Dr Stamey and his colleagues at Stanford and Dr Walsh and his colleagues at Johns Hopkins are using differing clinical criteria to compare differing patient outcomes. As a consequence they have very different results, and therefore very different opinions about how to interpret those results. Surgery is not like boxing or wrestling. You cannot put the two surgeons in a ring with two scalpels and a patient and ask them to fight it out! Unfortunately, that is what happened in this situation.

It is the carefully considered opinion of The Prostate Cancer InfoLink that this whole controversy would be better forgotten and put behind us. At some time in the future, when the technology is better, the prognostic markers are better, the ability to define impotence and incontinence accurately is better, etc., etc., we may be able to rationally address the disagreements between these two academic camps. At the moment, we can not. Suffice it to say that everyone seems to have forgotten the final two sentences in Dr Stamey's original article, which are quoted below. We have added the italic emphasis.

"It is an awesome responsibility for the surgeon to present the options to a patient with prostate cancer in such a way that he does not impose his prejudices, which may or may not be based on the best objective information. I have prepared these comments with the hope that my own patients will find it easier to make the right decision as to how their prostate cancer should be treated, regardless of what I tell them."

These two sentences are perhaps of far greater importance than all of the rest of the controversy.

The fact of the matter is that Dr Walsh and Dr Stamey agree about many more major issues than the number they disagree over.

  • They agree that surgery for localized prostate cancer is first and foremost a procedure which is intended to try and cure the patient.
  • They agree that sparing the neurovascular bundles should only be attempted in those patients for whom this will not affect the potential ability to remove all of the cancerous tissue in the prostate.
  • They agree that patients with cancer-positive surgical margins are at very high risk of recurrent prostate cancer.
  • They agree that patients should be very carefully evaluated prior to any decision about the appropriate method of treatment.
  • They agree that prostate cancer patients should make every attempt to understand the risks and benefits associated with the different treatment options available.
Now if you've got this deep into The Prostate Cancer InfoLink, you have probably worked out that there really are no easy answers for anyone in the management of prostate cancer. Why should any of us be surprised if two of the world's leading experts on the surgical management of prostate cancer have some strong disagreements over how to interpret and address certain types of clinical and scientific data?

External beam radiation therapy

[Reminder: this document was last revised in 1997. Procedures may have changed.]


According to the National Cancer Institute, potentially appropriate candidates for definitive radiation external beam therapy who have localized disease are patients with stage T1b or T2 disease. A review of data from 999 patients treated with radiotherapy indicates that 79% of T1 patients treated with external beam radiation were alive or had died of causes other than prostate cancer at 10 years as compared to 66% of patients with stage T2 disease. The National Cancer Institute also states that patients with a PSA level higher than 15 ng/ml will probably fail external beam radiation therapy.

It is important to understand that just as surgical techniques have evolved in the recent past, so have the techniques of radiation therapy. Probably one of the most important advances in the most recent past is the ability to use three-dimensional conformational planning, which is a method which allows for the more accurate delivery of the radiation to the prostate, and the avoidance of excess and unnecessary radiation of surrounding tissues. However, it will be some years before long-term survival data from radiation therapy with conformational planning is available. As a result it is unwise to speculate about the long-term value of this new technique or its impact on patient outcomes.

In principle, external beam radiation therapy uses a system for the delivery of high-powered radiation to the prostate and immediately surrounding parts of the anatomy. The radiation is carefully designed in so far as possible to kill the prostate and prostate cancer cells. Various methods have been used in order to try to direct the radiation accurately to the prostate and to minimize extraneous radiation of surrounding tissues. As yet, no other form of radiation has been shown to be as effective in the treatment of prostate cancer as external beam radiation.

Who should consider radiotherapy for localized disease?

A number of specific type of individuals may wish to external beam radiotherapy instead of radical surgery for the treatment of their prostate cancer. And there are certain patients for whom radiotherapy may clearly represent a better clinical option or may just be a preferred personal choice.

The most obvious situation in which radiotherapy is clearly a better option than surgery is for patients who are poor candidates for surgery because of other medical risk problems. Such patients can be treated with external beam radiotherapy with good results and low complication rates and without the risks that come with surgery. Another group for whom external beam radiation may be an excellent choice is patients who do not wish to take the risks associated with removal of his prostate. In either case, the patient should still conform to the recommended guidelines indicated earlier: stage T1b or T2 with a PSA of 15 ng/ml or less. It is normal for such patients to be given a bone scan in order to confirm that there are no signs of metastatic prostate cancer prior to radiotherapy.

What is actually involved in external beam radiotherapy?

In the first place, the radiation oncologist will carry out a simulation of your radiotherapy. Depending upon the capabilities of each individual clinical practice, the complexity of this simulation will vary. However, the objective is to set up a system which will ensure the delivery of the most appropriate dose of radiation to a particular patient's prostate, depending upon the size and position of that prostate and its location relevant to other nearby organs.

The most sophisticated form of such simulation is "three-dimensional conformational planning," which is currently available at a limited number of centers, but will soon become more widespread. Other centers presently use a variety of x-ray, ultrasound, CT scans, and similar techniques to plan the delivery of radiation therapy.

Actual treatment can begin shortly after the treatment planning is completed. A full course of external beam radiation usually takes about 6 and 8 weeks, with a "fraction" of the total radiation dose being delivered each week day. It takes about 10 to 15 minutes each day to deliver one "fraction" of the total dose. Unfortunately, it is not really possible to modify this radiation dosing schedule because of the way in which cancer cells grow and the way in which radiotherapy acts on those cells. By delivering the radiation for 5 days each week, the body is able to recover for two days each weekend.

From a physical point of view, external beam radiation therapy is relatively easy for the patient. Each day he gets to go to the radiotherapy center and lie on a treatment table while the radiation therapist moves a carefully aimed x-ray machine over a targeted area of the patient's lower abdomen, sides, and back. This is certainly a great deal less invasive than radical surgery.

Is external beam radiotherapy as good as radical surgery?

This is the $64,000 question to which no one has an answer. As a patient, the best thing that you can do is carry out your own risk/benefit analysis and ask yourself some hard questions.

Here are the clear advantages of external beam radiation compared to surgery:

  • There is no surgery and no anesthesia, so there is lower morbidity and mortality.
  • There is no risk from surgical bleeding and transfusion.
  • The rate of impotence resulting from radiation therapy is generally less than that from surgery.
  • Incontinence rates are generally low (at less than 5%).
  • There is good long term control of the cancer.
On the other end of the scale, there are some clear disadvantages:

  • There is a 10-15% possibility of radiation damage to the bladder and/or the rectum.
  • The rate of long-term impotence is about 30-50%.
  • There is a rare occurrence of serious side effects such as radiation-induced cystitis, proctitis, and enteritis. These are usually reversible but may be chronic and can occasionally necessitate surgical intervention.
  • Therapy takes 6-8 weeks compared to a few days.
As with radical surgery, radiation therapy tends to be more difficult in patients who have had a prior transurethral resection of the prostate (TURP). According to the National Cancer Institute, definitive external beam radiation therapy for patients with localized prostate cancer should be delayed for 4-6 weeks after a TURP because of the risk of urethral stricture (constriction or narrowing of the urethra). In the study of patients with localized prostate cancer treated in a managed care setting (mentioned earlier under the discussion of complications of radical prostatectomy), radiation therapy was associated with substantial sexual and urinary problems. However, we would again note that this study included patients whose diagnosis of prostate cancer could have been as early as 1961. We would suggest that external beam radiation treatment for prostate cancer today would be associated with notably lower levels of adverse reaction than in the 1960s or 1970s.

The question which inevitably is raised by the advocates of surgery is whether radiation therapy does in fact cure prostate cancer. Definitive proof that radiation therapy can cure localized prostate cancer is not available. While PSA levels can be reduced to very low levels following radiation therapy, the dead prostate cancer tissue remains in the body (at least for a while). Therefore we do not see the rapid reduction in the PSA levels to undetectable which can be seen after radical surgery.

In addition, it appears that while the results of surgery include disease-free survival as indicated by undetectable PSAs out beyond 10 years, the results of external beam radiation are less reliable based on PSA data. Control of prostate cancer appears to be approximately equivalent for about 7-10 years. The question is really whether surgery can offer benefits over radiation for patients young and healthy enough to benefit from extended disease-free survival (say 15-20 years), and then at what cost.


[Reminder: this document was last revised in 1997. Procedures may have changed.]


Brachytherapy is a form of radiation therapy in which physicians implant radioactive pellets or "seeds" into the prostate gland in order to kill prostate and prostate cancer cells. Although there are no data providing a direct comparison between the results of this technique and any other form of treatment for localized disease, the data now available from selected centers would suggest that brachytherapy is potentially as effective as and may be safer than either radical prostatectomy or external beam radiation therapy for some patients when carried out by physicians with appropriate levels of experience.

The great benefit of brachytherapy to the patient as compared to external beam radiation is that it is carried out in a single procedure, and therefore does not require the multiple visits necessary for external beam radiation. Having said that, it should also be recognized that many centers combine brachytherapy with a short course of external beam radiation in order to offer the best of both treatment modalities.

At present, the available long-term data on the use of brachytherapy are limited to 5-7 years of follow-up, which is not sufficient to establish any true efficacy or safety comparison with other forms of treatment. However, the availability of new techniques for seed implantation under transurethral ultrasound guidance, and the availability of new forms of radioactive seed made with palladium, iridium and other radioactive elements, which give off low energy forms of radiation within relatively short time spans, do suggest that in time we may be able to document the true value of brachytherapy in the management of prostate cancer relatively soon.

Who might consider brachytherapy?

Patients who are potentially appropriate candidates for brachytherapy could well include some patients with localized disease. However, it is hard to tell exactly which patients might be the most appropriate candidates.

Urologists would probably argue that brachytherapy is inappropriate for any patient who is a definite candidate for nerve-sparing prostatectomy, and they have a case. Brachytherapy, like any form of radiation, is associated with a significant incidence of post-treatment impotence -- although reliable data are not currently available for large numbers of patients. On the other hand, brachytherapy may well be an excellent option for some patients with stage T1 or T2 prostate cancer because in their cases surgery might result in positive surgical margins and nerve-sparing surgery is not an option.

In the end the patient must make decisions about the possible value of brachytherapy himself in consultation with his doctors. Things which should influence the patient's decision include:

  • Will your insurance cover this procedure?
  • How many brachytherapy procedures has the physician you are talking to carried out, and what are the short-term and long-term results of those procedures?
  • Does the physician intend to try to cure your cancer using brachytherapy? In other words, would he expect to be able to offer you 10 or more years of disease-free survival as a result of this procedure?
  • What is the incidence of short-term and long-term impotence and incontinence among patients who he has treated using brachytherapy?
  • Can the physician give you references to two or three other patients who he has treated in the manner he is proposing for you?
The Prostate Cancer InfoLink suggests that at this time it is unwise to agree to proceed with treatment using brachytherapy without seeking at least one other clinical opinion on appropriate therapy for your individual condition.

How is brachytherapy carried out?

[Reminder: this document was last revised in 1997. Procedures may have changed.]

If you wish to read a detailed description of the procedural techniques for carrying out brachytherapy, please click here. [The proposed document was not created before the site closed. For one source on the procedure, click here.]

Side effects of brachytherapy

Brachytherapy has been associated with such long-term adverse reactions as proctitis (in 1% of patients receiving iodine-125) and impotence (in about 20% to 30% of patients at 3 and 1 years respectively). In addition there are multiple short-term side effects such as hematuria (blood in the urine) and hematospermia (blood in the ejaculate). However, there are few carefully analyzed data available which offer objective reports on adverse reactions following brachytherapy. For example, there appear to be no data on incontinence and diarrhea following brachytherapy, although these are well-known adverse reactions to external beam radiotherapy.

The problem of radiation safety

[Reminder: this document was last revised in 1997. Procedures may have changed.]

Although the radiation risks associated with radioactive seed implants are low, there are certain additional precautions that are important to know about before you decide to undergo brachytherapy:

  • It is possible to pass radioactive seeds in your urine for a while after the procedure. This means that you have to filter your urine for a while.
  • You are asked to stay at least a few feet away from young children and pregnant women for a couple of months after the procedure, so if having your grandson or granddaughter sit on your lap every evening while you read stories is a big part of your day, brachytherapy may not be for you!
As you can see, these radiation risks are low risks to others. However, since they may have significant impact on your lifestyle for a couple of months they may be important. Brachytherapy could, for example, present significant problems for a man who shared accommodation with a young couple with a couple of children and another one on the way.


[Reminder: this document was last revised in 1997. Procedures may have changed.]


Cryosurgery is not a new technique. Rather it is an old technique which has been given a new lease on life by the use of improved methods and equipment. It also has many names. You may find that the people you talk to about this call it cryotherapy or cryoablation or simply "cryo."

The basic concept behind cryosurgery is that the cryosurgeon can use extreme cold to freeze the prostate, which causes the cells to break down as they are first frozen and then thaw. The freezing process is accomplished by the use of metallic probes which circulate liquid nitrogen at -195 F. Modern prostate cryosurgery is usually carried out by urologists who are very familiar with the techniques of transrectal ultrasound because ultrasound techniques are used to monitor the development of the so-called "ice-ball" which grows around the prostate and associated tissues during this technique.

There are currently many unanswered questions that surround the potential of prostate cryosurgery. Patients should be aware that this is not a widely accepted procedure for the treatment of prostate cancer at the current time. Many experts consider this technique to be experimental, and The Prostate Cancer InfoLink considers that patients who wish to be treated by this technique should see if they can do this within a clinical setting that is dedicated to the accumulation of greater knowledge about the real value of this procedure. The current status of this technique also means that there can be difficulties in obtaining health insurance coverage for this procedure.

The Prostate Cancer InfoLink also recommends that patients consider cryosurgery only by physicians at centers where there is significant expertise in this technique. Dr Gary Onik, a recognized authority on the use of cryosurgery in the treatment of prostate cancer, has provided a review of current knowledge appropriate for patients in an article entitled "Percutaneous prostate cryoablation."

The questions about cryosurgery

Certain aspects of cryosurgery are potentially very attractive to patients and to surgeons. For example, it requires only a brief period of hospitalization and the patient has an excellent chance of retaining complete urinary continence almost immediately after the procedure. However, there is a whole series of unanswered questions:

  • Can cryosurgery actually cure prostate cancer?
  • Can cryosurgery actually eliminate prostate cancer cells from the prostate?
  • Should effective cryosurgery reduce PSA to undetectable levels?
  • Can a definitive clinical trial be developed that will compare cryosurgery to other forms of therapy?

Until at least some of these questions are answered, it will be hard for the medical community to decide what the precise role of cryosurgery should be in the management of prostate cancer. However, it does seem likely that there will be a future role for cryosurgery in the management of prostate cancer. Some of these will be dealt with in other parts of this section on treatment.

Can cryosurgery cure localized prostate cancer?

Currently available data appear to indicate that at about 2 years after treatment at least 20% of patients have a biopsy positive for prostate cancer and a high percentage of patients have an elevated PSA level. There are no available data as yet on disease-free survival of patients who have lived for 5 or more years after cryosurgical treatment.

In order to be sure of a cure for prostate cancer that is localized to the prostate, it is generally agreed that one must either kill or remove from the body every possible prostate cancer cell, and the only way to be sure that this has happened is to kill or remove from the body every piece of prostate tissue. Unfortunately we cannot be sure that that happens in cryosurgery.

In order to preserve urinary continence, during cryosurgery the surgeon places a special catheter into the urethra. This catheter warms the urethral tissue and prevents it from freezing. However, the result is that prostatic tissue immediately surrounding the urethra is also warmed, and therefore is not destroyed by the freezing process. If there are prostate cancer cells in the prostate tissue immediately surrounding the urethra, then these cells are unlikely to be destroyed, so every prostate cancer cell will not be killed.

Now to be fair to the advocates of cryotherapy, not all prostate cancers include foci of prostate cancer close to the urethra, so there may well be patients in whom all of the prostate cancer can be destroyed by this procedure. As usual, however, the question then becomes one of whether we can tell beforehand which patients are actually the ones most appropriate for cryosurgery.

Can cryosurgery actually eliminate prostate cancer cells from the prostate?

It is customary today that before a new medical technique is used extensively on humans we have learned a great deal about it by laboratory research work on animals and human tissue. The laboratory work related to cryosurgery has been relatively limited.

This relative lack of laboratory information does not mean that cryosurgery will not actually kill or eliminate prostate cancer cells from the body. However, it does mean that there are all sorts of unanswered technical questions raised by the scientific and clinical research community. The lack of answers to these questions makes it difficult for most physicians to feel that cryosurgery has absolutely demonstrated its value. This is particularly important if one considers the use of cryosurgery in localized disease where the intent is often to cure the patient of his prostate cancer.

Should effective cryosurgery reduce PSA to undetectable levels?

We know that if radical prostatectomy is to be successful, the patient's PSA level should be zero or undetectable after the operation. It is also widely agreed that radiotherapy is much more likely to be successful if the patient's PSA falls to zero or undetectable levels after treatment. Is it therefore reasonable to assume that the same should be true for cryosurgery?

We already know that at least a small amount of living prostate tissue must be left behind after cryosurgery because of the need to warm the urethra and the tissue immediately surrounding it. If we leave live prostate tissue behind, it will be capable of producing PSA. Therefore it is probably unreasonable to believe that the PSA should fall to zero. So now we are faced with the question, "How can we tell if the cryosurgery has been effective?"

Can we develop definitive clinical trials of cryosurgery?

We have never been able to prove that radical prostatectomy or external beam radiotherapy are effective for the treatment of prostate cancer relative to each other or any other form of therapy. It therefore seems highly unlikely that we will ever be able to prove that cryosurgery is any more or less effective than cryosurgery or radiation therapy in a randomized controlled trial. The best that we are going to be able to manage in the short term will be very careful evaluation of the results from patients treated using cryotherapy over the next 10 to 15 years. What percentage will have rising PSA levels over what period of time? How many will die from prostate cancer after what time periods? Exactly what were the stage and grade of disease of those patients when they underwent therapy?

Because it is so important to try and find out whether cryosurgery really does work, The Prostate Cancer InfoLink strongly encourages patients who wish to undergo cryotherapy to have such a procedure only at a center which is committed to the careful collection and analysis of appropriate data about cryotherapy over time. Such a center will probably want you to come back regularly for PSA checks for the rest of your life if at all possible, and will want you to provide a very considerable amount of preoperative information so that they can establish a sound basis for their research.

Who should consider cryosurgery?

Because cryosurgery is still an experimental technique, this is a very hard question to answer. However, there are a few definite facts which should be taken into consideration:

  • Cryosurgery does not appear to be successful for patients with large prostates. If your prostate weighs more than about 40 grams, you should be extremely cautious before agreeing to undergo cryosurgery. However, this situation may change as the procedure is refined and improved.
  • Cryosurgery appears to be harder to perform in men who have already had a transurethral resection of the prostate (TURP).
  • Cryosurgery is not a nerve-sparing procedure. In order to be sure that all of the prostate tissue is properly frozen, most cryosurgeons will also freeze within the ice-ball the nerves on the surface of the prostate that are associated with successful erection.

Patients who wish to attempt cryosurgery for the treatment of localized prostate cancer could include older patients for whom highly invasive surgery would be a risk or younger patients for whom urinary continence is more important than sexual potency and the risk of recurrent prostate cancer.

Complications of cryosurgery

Because ultrasound-monitored cryosurgery is a relatively new technique, our accumulated knowledge about the complications is limited. However, here is the available information to date.

Up to 80% of cryosurgery patients are impotent after the procedure, and it appears that there is a relationship between the degree of impotence and the way in which the cryosurgeon manipulates the ice-ball in order to maximize effective freezing of potentially cancerous tissue. The degree to which patients may be able to recover their potency in the long term is currently unknown.

Many patients notice irritation to the bladder or the urethra which can be associated with a variety of additional symptoms, including the frequent need to urinate with little "warning," a burning sensation or pain on urinating, or blood in the urine. Some patients also mention irritation of the rectal wall. In addition, about half of cryosurgery patients mention penile or scrotal swelling. All of these adverse reactions appear to be temporary.

There are some less common but potentially serious complications of cryosurgery. In the first place, some men find that they have scarring of the urethra and others have difficulty urinating. These problems may require catheterization on a temporary or perhaps permanent basis. The most serious complication of cryosurgery is the potential formation of a "fistula," which is an abnormal connection between the urethra and the rectum. This requires surgical intervention for treatment.

Neoadjuvant and adjuvant hormonal therapy

[Reminder: this document was last revised in 1997. Procedures may have changed.]


There appears to be an increasing tendency toward combining hormone therapy with other forms of therapy for the treatment of localized prostate cancer.

The theory behind this tendency is that by initiating hormonal blockade before and/or after the primary form of therapy (e.g., radiation) one (a) delays any progression which might occur prior to implementation of the potentially curative treatment and (b) in some way or other maximizes the likelihood that the curative treatment will, in fact, be truly curative. To what extent these uses of neoadjuvant and adjuvant hormonal therapy are a result of patient demand, a consequence of general theoretical belief, or just economic pressure is completely unknown. However, there are a rapidly increasing number of clinical trials in development which have been designed to test the validity of these concepts. Recently, the US Food and Drug Administration endorsed this form of therapy by its approval of flutamide in combination with an LHRH agonist and radiotherapy for the treatment of stage T2b and stage T3 prostate cancer.

What are "neoadjuvant" and "adjuvant" hormonal therapies?

"Neoadjuvant" hormonal therapy is hormone therapy which is given prior to, but in association with, some other form of therapy; for example, a physician might decide to treat a patient by giving him hormone therapy before carrying out a radical prostatectomy or external beam radiation. Similarly, "adjuvant" hormonal therapy is hormone therapy which is given at the time of or following, but in association with, some other form of therapy; in this case the physician might decide to give the patient hormone therapy immediately following a radical prostatectomy or external beam radiation. Obviously, some patients may receive both neoadjuvant and adjuvant hormonal therapies.

The most common forms of neoadjuvant and adjuvant hormonal therapies are the following:

  • Neoadjuvant therapy with 1-3 months of an LHRH agonist prior to treatment with surgery, radiation, or cryosurgery
  • Neoadjuvant therapy with 1-3 months of maximal androgen deprivation (i.e., an LHRH agonist + an antiandrogen) prior to surgery, radiation, or cryosurgery
  • Adjuvant therapy with 3 or more months of an LHRH agonist subsequent to surgery, radiation, or cryosurgery
  • Adjuvant therapy with 3 or more months of maximal androgen deprivation (i.e., an LHRH agonist + an antiandrogen) subsequent to surgery, radiation, or cryosurgery.
  • Adjuvant therapy with 3 or more months of an oral antiandrogen subsequent to surgery, radiation, or cryosurgery.

At least some oncologists and selected radiation oncologists appear to be among the most ardent advocates of neoadjuvant hormonal therapy, as indicated by the detailed review of this topic by Drs. Strum and Scholz (Neoadjuvant Hormone Blockade in Prostate Cancer) and their related article on the informational rights of prostate cancer patients (A Medical Miranda for the PC Patient). On the other hand, there are other physicians who have made it clear that they have grave doubts about many of the current uses of hormonal therapy in any patients except those with symptomatic stage D2 disease. For example, Dr Walsh at Johns Hopkins apparently will not operate on any patient who has received hormonal therapy.

Other pharmaceuticals have also been used in adjuvant and neoadjuvant settings, including finasteride and diethylstilbestrol (DES). None of these pharmaceuticals have been indicated by the US Food and Drug Administration for use in adjuvant or neoadjuvant treatment of localized prostate cancer.

The Prostate Cancer InfoLink considers that, with the exception of neoadjuvant and adjuvant maximal androgen deprivation in combination with radiotherapy for stage T2b and T3 disease, such uses of hormonal therapy are still investigational. We are awaiting information that shows a true survival benefit to neoadjuvant and adjuvant therapies for the prostate cancer patient. We believe that in time such information is likely to become available. However, it is not available yet. In some cases, anecdotal information is clear that neoadjuvant therapies have been offered to patients in order to allow the patient time to deal with personal issues before undergoing surgery or radiation therapy. Because prostate cancer is a very slowly growing disease, the value of such forms of treatment is unknown and may be open to question.

Current clinical data on neoadjuvant and adjuvant hormone therapies in localized disease

There is very little current data on the use of neoadjuvant and adjuvant hormone therapy in localized disease. The Prostate Cancer InfoLink is aware of only two clinical trials from which significant information is currently available.

In one such trial, the investigators randomized patients with clinical stage T2b disease to 3 months of neoadjuvant maximal androgen deprivation with goserelin acetate + flutamide or no prior therapy. All patients went on to receive a radical prostatectomy. Although this was a small trial, the results clearly showed that patients receiving neoadjuvant maximal androgen deprivation were less likely to have positive surgical margins than the patients who received no neoadjuvant therapy. On the other hand, the surgeons clearly believed that the surgery was more difficult and took longer in the patients who had received the neoadjuvant therapy.

In another, larger trial, the Radiation Therapy Oncology Group (RTOG) randomized patients with clinical stage T2b, T3, and T4 disease to receive neoadjuvant and adjuvant maximal androgen deprivation with goserelin acetate + flutamide or no neoadjuvant or adjuvant therapy. All patients went on to receive external beam radiation therapy. Again, this trial has suggested a clinical benefit to the use of neoadjuvant and adjuvant therapy. However, the data are still unpublished. However, it is on the basis of this trial that flutamide was recently approved in combination with an LHRH agonist and radiation therapy for the treatment of stage T2b and T3 disease.

According to data received from Schering-Plough Corp., the RTOG trial showed the following detailed results:

  • Patients receiving hormonal therapy + radiotherapy had significantly increased median survival (4.4 years vs. 2.6 years) compared to those receiving radiation alone.
  • Patients receiving hormonal therapy + radiotherapy demonstrated a lower rate of local failure (16% vs. 33%) at 4 years than those receiving radiation therapy alone.
  • When normal PSA levels were included as a criterion for disease-free survival, patients receiving hormone therapy + radiation again demonstrated a significantly increased median disease-free survival (2.7 years vs. 1.5 years)

We should conclude that while there is some interesting information to suggest that there are benefits to the use of adjuvant and/or neoadjuvant hormonal therapy in the treatment of localized prostate cancer, it is not yet certain that these benefits include extended overall survival. There are a number of clinical trials currently in various stages of implementation and development which have been designed to try to determine whether there is a real survival benefit to this type of therapy.

The complications of neoadjuvant and adjuvant hormonal therapy

As indicated above, it seem clear that neoadjuvant hormonal therapy makes radical prostatectomies more difficult for surgeons (at least when they start carrying out procedures on patients who have received this type of therapy). As a consequence, we must seriously question whether pre-treating surgical patients with maximal androgen deprivation is really worthwhile. The other risks of neoadjuvant hormonal therapy are primarily the risks associated with taking the necessary pharmaceuticals for significant periods of time. Brief comments on the side effects of all of the relevant pharmaceuticals can be found in the section on pharmaceuticals used in the treatment of prostate cancer.

Post-surgical radiation therapy

Unfortunately, there is a significant number of patients who, immediately following surgery, are discovered to have "positive surgical margins." In addition, there is a second group of patients who are found to have prostate cancer-positive seminal vesicles. This means that despite the best attempts of the surgeon, in carrying out the prostatectomy he or she actually was unable or may have been unable to remove all of the cancer and there is a good chance that there are cancer cells left in the tissues which remain. The pathologist can tell this from a careful examination of the surface of the prostate and the seminal vesicles after surgery.

Although the patient's disease is still "localized," it is now necessary to treat the patient in some way in order to try and kill these remaining prostate cancer cells. It is customary to do this by the use of adjuvant external beam radiation therapy. While there is no proof that such adjuvant radiation therapy actually improves survival for patients with positive margins or positive seminal vesicles, it is clear that it does reduce the frequency of local recurrence of the disease.

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The content in this section of the Phoenix 5 site was originally developed by CoMed Communications (a Vox Medica company) as part of The Prostate Cancer InfoLink. It is reproduced here with the permission of Vox Medica.

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