Prostate Cancer Decision Guide
- What is PSA?
- Natural History of Prostate Cancer
- How Worried Should I Be?
- Two Important Questions – Difficult to Answer
- Risk Groups
- Treatment Options
- Watchful Waiting
- Hormone Therapy
- External Beam Radiation Therapy
- What is the Best Treatment?
- Treatment Options by Risk Group
- Follow-Up Care and PSA Monitoring
- Frequently-Asked Questions
You’ve been diagnosed with prostate cancer. If you’re like most men, this happened because your doctor noticed on a routine blood test that your PSA value was over 4 or was rising rapidly. He may or may not have detected a lump or irregularity in your prostate on a rectal exam. He referred you to a urologist who took multiple biopsies of your prostate, and the pathologist found evidence of cancer.
What do you need to know now? Plenty. And it’s going to be confusing. There are lots of facts, lots of opinions, lots of variations, and very few good scientific studies to guide you. You should read the information here, and other information that is available online or in books. You should plan to talk to at least one radiation oncologist, in addition to the urologist you’ve already seen. You should not panic, or even hurry to make a decision.
The information here reflects the way I approach prostate cancer, after more than thirty years of experience in radiation oncology. I have tried to make it clear what is opinion and what is fact, but inevitably my outlook is colored by being a radiation oncologist. If this were written by a urologist (as is the case with ALL the paperback books on prostate cancer in your bookstore!) it would undoubtedly read differently. Read this as a counterpoint, if nothing else.
No one can practice medicine at a distance, and nothing here should be construed as advice for you as an individual. Use this information to formulate questions for your own doctors. If you have a reasonable command of all these basics, then when you sit down with me, with one of my excellent partners, or with another doctor to make decisions we can get right to the specifics of YOUR case and what choices are the best ones for YOU.
WHAT IS PSA?
Prostate specific antigen (PSA) is a small protein molecule that is made in prostate cells, both normal and malignant. PSA is secreted into seminal fluid, where it facilitates the movement of sperm cells in fighting their way to the egg. It is very abundant in semen, but some PSA also “leaks” into the bloodstream and can be measured. Any man with a prostate will have some measurable PSA in his blood (serum). A man with an enlarged prostate (benign prostatic hypertrophy, BPH) often has a larger amount of PSA. Prostate cells that become malignant also make PSA. It is not completely clear whether the malignant cells make more PSA, or whether it simply leaks out into the bloodstream more, but a rising PSA is a sign that prostate cancer might be present. Doctors use “free PSA” (PSA that is not bound to another protein in the serum) and “PSA density” (serum PSA divided by prostate gland size) to try to decide which men should have a biopsy of the prostate. Once a man has been diagnosed with prostate cancer, as you have, free PSA and PSA density are of no further value.
NATURAL HISTORY OF PROSTATE CANCER
Prostate cancer is different from all the other common malignancies, in many ways:
- PSA. Measurement of PSA gives us a way to monitor the disease that is unique among common cancers. When the PSA is rising, it indicates cancer progression. When it is low and stable, or undetectable, it indicates cancer control. Some prostate cancers seem to make more PSA than others. In general, we worry more about high PSA than low, but in any man’s particular case, the pattern of his PSA movement is more important than the actual level of PSA. Lack of movement almost always indicates lack of disease progression. It is worth mentioning here that prostate cancer cells, even when they have spread to the bones, are still prostate cells and therefore they still make PSA. Measurement of the PSA can be an indicator of the amount or rate of spread, even to the bones. On the other hand, we can never be completely sure whether a man’s detectable PSA is coming from the prostate gland, from disease that has spread to the bones, or both.
- Prevalence. Most very old men actually have prostate cancer when they die of something else, if they have an autopsy to look at the prostate gland. The prostate cancer did not kill them, or cause any symptoms, or influence their lives in any way. It was simply there. Knowing about it would have produced anxiety, and perhaps a desire to undergo treatment, but such treatment would obviously have been unnecessary in those cases since death came from other causes. It would be better not to know, and therefore not to worry. We call these “autopsy cancers”, meaning that they are only important at autopsy. Most men do have “autopsy cancers” at age 80 or 90. Many men have them at age 70. The numbers are hard to get exactly, but it appears that some men, even at age 50 or 60, have small prostate cancers that will never grow, or will grow so slowly that they will never become a factor in the man’s life. It would be good to be able to tell these “autopsy cancers” from cancers that are destined to progress, but it is not possible to see the future in an individual case. Statistically, however, cancers that are not extensive within the prostate gland, not aggressive in appearance under the microscope, and not producing a rapid PSA rise may well be “autopsy cancers” and therefore deserve real thought before proceeding with treatment that may cause side effects and no survival benefit. PSA testing probably should be discontinued in men over about 80, since at that point it is much more likely to produce worry and trigger unnecessary treatment than to prolong life or prevent problems.
- Growth rate. Even if untreated, or if not controlled by treatment, prostate cancer tends to progress much more slowly than most other cancers. A man with untreated lung cancer is unlikely to live a year, while a man with untreated prostate cancer may very well live a decade. A prostate cancer that has grown enough to bring attention to itself in the form of a lump or an elevated PSA has probably been present for at least a couple of years. Therefore, there is almost never any urgency to jump into treatment. A man can afford to take plenty of time to consider the options and make a good decision.
- Mode of spread. Prostate cancer can spread locally in the pelvis, sometimes producing difficulty with urination or bowel movements. It can also spread to lymph nodes, and through the bloodstream. The usual site of distant spread (metastatic disease), if it occurs, is the bones. Prostate cancer seems to “like” spreading to the bones, and in many cases it never spreads anywhere else. This is both good news and bad. Bone involvement can be painful, but the pain can often be relieved by radiation therapy. Bone involvement is not a direct threat to life, as would be the case with spread to the lungs, liver, or brain, which we commonly see in lung cancer and breast cancer. It is possible to live for many years with spread to the bones, but in general the course is downhill with a declining quality of life. Sometimes it is hard to tell whether death is ultimately caused by the cancer or simply by debilitation.
- Difficulty in measuring results. The age spectrum of men at the time of discovery of prostate cancer is older than in any other common cancer. This leads to the above concerns about whether treatment is necessary at all in some men. It also complicates prostate cancer statistics. How do we measure a “cure”? If a man is treated for prostate cancer at 70 and dies of a heart attack at 90, was he cured of his cancer? What if his heart attack comes instead at 71? Should he be counted as a success or a failure? If a man’s PSA is slowly rising after treatment, when he dies in a car accident, was he cured? Would the findings of an autopsy make a difference? It is very difficult to compare “apples to apples” between prostate cancer studies, and therefore very difficult to say whether there is a “best” treatment. Other sources of statistical confusion will be discussed later when we are considering treatment options.
HOW WORRIED SHOULD I BE?
As a cancer specialist, when I first meet a man with prostate cancer, there are four things that I want to know:
- Gleason Score. How aggressive does this tumor look under the microscope? Although the “official” Gleason scale goes from 2 to 10, we simply never see scores less than 6. A total score of 6 is considered low. A total score of 8, 9, or 10 is high. A score of 7 is intermediate. Read more about the details of the Gleason score here.
- Stage. How much cancer is present in the prostate? More cancer is obviously worse. If there is nothing that can be felt with a finger or seen with ultrasound, we assign a stage of T1. For historical reasons, a stage of T1C is assigned to a man whose cancer was found only because of a PSA elevation that led to his biopsy. If there is a lump, the stage is T2, and further classified as T2A, T2B, or T2C according to how much of the gland the lump involves. If the cancer can be shown to have extended outside the gland, it is T3. T3A is simple extension beyond the capsule, while T3B is involvement of the seminal vesicle.(While Stage is the most convenient single factor in denoting the extent of disease, two other factors are important. One is whether the pathologist sees evidence of perineural invasion — cancer cells following along tiny nerves running through the prostate. This is correlated with a higher chance of finding invasion outside the gland, I think of it sort of like mice getting in and out of a house by following the pipes and wires through the walls. The second is how many of the biopsy cores contain cancer, and how much cancer they show. If two men both have Stage T1C, but one has only a tiny bit of cancer in one biopsy core and the other has all twelve cores full of cancer, it’s pretty clear that one is in more danger than the other. These factors don’t show up in the literature much yet, but they’re being watched closely.)
- PSA. How high is it, and how quickly is it rising? We don’t always have the information we would like, but it appears that the rate of rise of PSA may be even more important than the actual value. If we have two or more PSA values separated by time, we can calculate the PSA doubling time (PSADT) or the number of months that it takes for the PSA to double. A man with a quick doubling time has more to worry about than does a man whose PSA is stable or barely moving.
- Who has the cancer? I want to know not only how old a man is, but how long he is likely to live. What other illnesses or medical issues does he have? How long do people in his family usually live? A man of 75 who takes no medications and plays tennis every day is very different from a man the same age who is diabetic, has had two heart attacks, and weighs 300 pounds. I also want to know if the man has any medical history, such as prior abdominal surgery, active inflammatory bowel disease, or prior treatment for cancer, that may influence the spectrum of risks from treatment of prostate cancer.
TWO IMPORTANT QUESTIONS, DIFFICULT TO ANSWER
Has the cancer already spread elsewhere in the body?
If cancer has already spread (metastasized), then there is no need to consider treatment of the prostate gland itself, because the horse is out of the barn. Instead, we need to treat the whole body. There are three main tests available, but none is infallible.
- Since prostate cancer, if it travels at all, usually travels to bones, a bone scan is the most common test. Unfortunately, a bone scan is both too sensitive, and not sensitive enough, to be a decisive test. It can show any area of bone injury, old or new, including simple arthritis. And it can NOT show a few prostate cancer cells in the bones, unless they are causing enough bone injury to detect. For this reason, when the PSA and Gleason score are low, a bone scan is more likely to show false results than true results. The American Urologic Association (AUA) recommends that we NOT do a bone scan unless the PSA is over 20. Although this is based on excellent statistical evidence, many doctors feel that this is too conservative, and they ask for a bone scan when the PSA is over 10.
- Another place prostate cancer can go is to the pelvic lymph nodes, which are best investigated by CT scan or MRI scan. Because of poor ability to show very early spread, the AUA again says that this testing is unnecessary for men whose PSA is under 25.
- The Prostascint scan uses a radioactive tracer molecule that grabs onto PSA wherever it is found. If it shows PSA in areas where there should be none, it is suspicious for cancer. Unfortunately, the test is very expensive, somewhat unreliable, and of little use in a man who has a prostate gland because the tracer all ends up in the prostate, where PSA is abundant. It is sometimes used for evaluating a man who has had a prostatectomy but still has a rising PSA.
The bottom line is that, for a man who has a low PSA and Gleason score, it is usually best to do NO testing for disease spread, because the chance of finding false results is higher than the chance of finding true results that will influence the treatment decisions. Scans that are “normal” do not guarantee that there is no spread; they simply say that there is not enough disease to be reliably detected within the limitations of the scan. If and when a better scan comes along, it will change the decision tree.
Has the cancer already spread outside the limits of the prostate gland?
Once again, there is no scan or other test than can give a reliable answer, but there are good statistics. Statistics, however, can only tell the chance of an occurrence; they cannot tell whether it has occurred in any individual. Dr. Alan Partin and his colleagues at Johns Hopkins wanted an answer to this question, and they have given us the best answer so far.
Think of the prostate as something like a seedless plum, with a pulpy middle and a sort of skin, or “capsule” around the outside. The urethra passes through the middle. Prostate cancer starts in the pulpy part, and often spreads around widely within the gland. If it eventually escapes from the gland, it can go directly through the capsule, or it can spread to the seminal vesicles or to the lymph nodes. Partin’s group found about 5000 men for whom they had records of the PSA, Gleason score, and clinical stage, and who then underwent a radical prostatectomy. They re-reviewed all of the removed prostate glands to answer three questions: 1) was there extraprostatic extension (beyond the capsule)? 2) Was there spread to the seminal vesicles? 3) Was there involvement of any lymph nodes? The results, now refined several times, can be found in the Partin Tables if you click here.
As grade, stage, and PSA increase, the chance of cancer spread outside the prostate increases dramatically. Only in cases where all three factors are favorable is there a really high probability that all cancer is confined to the prostate, where it can reliably be removed by surgery.
SPREAD OUTSIDE THE PROSTATE IS EXTREMELY IMPORTANT.
If the cancer if truly confined to the prostate, then any effective treatment of the prostate is going to result in a cure. If the cancer has escaped the prostate far enough, however, it will not be killed by an attack on the prostate alone.
The pathologists involved in the Partin study were only able to study the prostate that was removed — not the tissues that were left behind in the patient. They could tell whether the cancer had penetrated outside the prostate, but not how far the cells had extended.
When a surgeon removes any cancer, he usually tries to also take a margin of healthy tissue around the cancer, just to be sure. This is impossible in prostate surgery. The bladder is above the prostate, the rectum is behind it, and the nerves controlling erections pass by on both sides. The most difficult part of the operation is the reconnection of the bladder and urethra, which occurs at the very bottom of the surgical field, deep in the pelvis. There simply is no way to take a generous extra margin. The prostate will be removed, but anything that has truly escaped the prostate will be left behind.
With all the variability involved in measuring the three important parameters — grade, stage, and PSA — it is necessary to start condensing a bit into groups of patients for whom the treatment decisions are similar. We call these “risk groups” and in this case the word “risk” is used rather loosely, both to describe the risk of spread outside the prostate and the risk of ultimately developing metastatic disease.
Low Risk has: Grade 3+3 or lower, and
Stage T2A or lower, and
PSA 10 or lower.
Intermediate Risk has: Grade 3+4 or 4+3, or
Stage T2B or T2C, or
High Risk has: Grade 4+4 or higher, or
Stage T3A or higher, or
PSA 20 or higher, or
Any combination of two factors from the Intermediate list.
The above risk groups can be “fine-tuned” a bit more by considering some additional factors. Men whose PSA is rising rapidly, or has risen by more than 2 points in the past year, are statistically at higher risk. Men who have a large number of positive biopsy cores are at higher risk than men whose cancer was found in only one or two cores, even though they might both be called stage T1C. Younger men have more to worry about than older men, simply because they have longer to live and their cancer has more time to grown. All of this, though, is to try to get a handle on how to choose a treatment that is adequate for your case, but without overtreatment.
First, let’s clarify that ALL treatments for prostate cancer are directed at the whole prostate. In many other cancers, only the diseased part of the organ is removed or treated, but in prostate cancer, whether you have surgery or another treatment, it will be directed at the whole prostate, even if your biopsy showed cancer in only one side, or even in only one tiny sample. We know from a long history of prostatectomies that, even when disease is expected in only one part of the gland, very often it will also be present in other parts. Currently, the best methods of looking at the prostate — magnetic resonance imaging and spectroscopy — are just not accurate enough to justify leaving part of the prostate in place. There is ongoing research, to try to identify men who could have treatment of less than the entire prostate, and thus perhaps better retention of sexual potency. But if you contemplate such treatment, be sure that it is done as part of a clinical protocol that is approved by the hospital where it is done. There is a danger that, when treating less than the whole prostate, some cancer cells will survive that would have been killed by conventional treatment.
I don’t really like this term, although it gets used a lot. “Expectant Management” is used sometimes as well. I prefer the term “Deferred Intervention.” In prostate cancer, it is usually not necessary to intervene at once. Many men who have prostate cancer are NOT going to die of it, and perhaps will never even be inconvenienced by it. If you have low risk disease, especially if your PSA is not rising rapidly and you don’t have a high percentage of positive biopsies, you should consider deferring intervention for a time to see if there is any progression. This is even more advisable if you are older, or have other medical conditions that limit your life expectancy, which you can look up by clicking here. You can monitor the PSA and rectal exams at intervals and have annual prostate biopsies. You can choose to intervene in a few months, or a few years, if there is progression.
Prostate cancer grows better in the presence of male hormones. Think of it as putting fertilizer on weeds: it doesn’t create the weeds, but it does make them grow better. If the fertilizer is withdrawn, the weeds will grow less well. Some of the weeds may even die for lack of fertilizer, though probably some will succeed in surviving. Dr. Charles Huggins received the Nobel Prize for his discovery, in the 1930’s, that men with advanced prostate cancer experienced dramatic improvement when they were castrated. In the modern day we rarely use actual castration, but drugs called LHRH Agonists have been developed to shut off the production of male hormones for up to several months after a single injection. Sometimes, additional drugs called anti-androgens are given in conjunction with the LHRH agonist. This is called “combined androgen blockade” but it is still a matter of some controversy as to whether it is superior to the LHRH agonist alone. As alluded to above, this is not a cure for prostate cancer, but it can be a remarkably effective treatment, sometimes able to control the progression of the disease for years, or even decades. It is an excellent choice for a man who already has evidence of spread, or a man who has very high risk disease or a limited life expectancy.
Hormone therapy is also often used in conjunction with radiation therapy, especially for patients with high risk disease. It appears to help in making the radiation therapy more effective locally, and also prevents or delays the appearance of cancer that may already have spread.
Blocking the male hormones has predictable side effects. Almost all men find that their sexual desire diminishes, as does their ability to have erections. Most men have hot flashes, similar to a woman going through menopause. These can range from temporary and mild to prolonged and very troublesome. With most men, the severity diminishes over time. If the hormone suppression is used for only a short period, the changes usually go back to normal when the drug is stopped and normal hormone production returns. Some men find that their sexual desire or performance is still impaired, however, especially if they have had radiation treatment simultaneously.
Men who stay on hormone suppression for a long period will experience changes in their body fat distribution which gives them a more “rounded” shape. They may be vulnerable to osteoporosis, cholesterol and diabetic problems and need to be monitored. Some men find that they have fatigue or lack of motivation that is insidious and troubling. As with most medications, LHRH drugs have their good sides and bad. Discuss your particular situation with your doctor.
This is a surgical procedure to remove the prostate gland entirely, along with some or all of the seminal vesicles and, sometimes, sampling or removal of the nearby lymph nodes. The bladder is then brought down and re-connected to the urethra so that urination is possible. This is a major operation and requires some weeks for full recovery. It has perioperative risks, as does any major surgery. It is always necessary to leave a catheter in place, usually for a matter of weeks, until the re-connection is strong and the man has trained himself to again be continent of urine. Most men regain excellent continence, though some do find that they are more likely after surgery to leak a little urine when they cough, strain, bend over, or change position, and therefore they wear an absorbent pad in their underwear. It is unusual to have more incontinence than this.
Essentially all men will be impotent (unable to have erections) immediately after a prostatectomy. Many years ago, this was always a permanent condition. Now it is possible to spare the nerves controlling erections, if the disease is not extensive, and many men get back their sexual function after some weeks or months, though they often find that they now need potency-enhancing drugs such as Viagra. Some men, though, never regain erections even when the nerves are spared. It is difficult to get good statistics on this. A fair guess would be that about 50% of men who have good erections before surgery will be able to return to acceptable sexual function. A man who already has trouble is less likely to recover function.
If you have a prostatectomy, be sure to ask your surgeon afterward about the stage of your tumor. If you had a T3 tumor, which means there was cancer extension outside the prostate or to the seminal vesicle, you should have radiation therapy after surgery. This is true even if the surgeon was able to get all of the cancer with a clear margin, and even if your postoperative PSA falls to zero. Two important studies, one from the US and another from Germany, have proved that the survival rate after prostatectomy for T3 disease is higher if radiation is added, but not all urologists are yet convinced. At the very least, you should have a consultation with a radiation oncologist.
Radical Perineal Prostatectomy
The surgeon makes an incision through the perineum, the area behind the scrotum and in front of the anus. This provides the most direct approach to the prostate. It has the disadvantage that it is not possible to remove lymph nodes or preserve the nerves that control penile erections by this approach. Although some surgeons still prefer this approach for certain situations, especially for very obese men, it is largely out of favor.
Radical Retropubic Prostatectomy
Here the surgeon’s incision is in the lower abdomen, and the prostate is approached by going down behind the pubic bone. Wider exposure by this approach makes it possible to remove lymph nodes if desired, and to find and protect the nerves controlling erections.
Laparoscopic Radical Prostatectomy
Instead of a large incision, several smaller incisions are made in the lower abdomen for the insertion of several instruments to see the prostate area and manipulate the tissues to remove it. Because there is no large incision, healing is usually faster. The procedure is more difficult for the surgeon, and requires special training and experience.
Robotic Assisted Radical Prostatectomy
This is a refinement of the laparoscopic prostatectomy in which one of the instruments inserted into the abdomen is a robotic arm that has the movements of a tiny surgeon’s hand and wrist. The surgeon doing the operation is actually sitting at a console and manipulating the controls of the robot, while watching a three-dimensional TV image of what is going on inside the body. Some surgeons like this, because they feel it gives them better vision and control. Others prefer the open prostatectomy, because they believe they can do the operation better with the ability to actually feel the prostate and bladder, which the robot cannot do.
The surgeon must take a training course and be monitored by an expert for his first few operations, because this really is a completely new type of surgery. Unusual complications can occur with inexperienced surgeons.
Nobody has done a prospective, randomized trial to prove whether one operation is better than the other but in 2009 the majority of prostatectomies done in the US were done robotically. Many surgeons hope that they will be able to offer better urinary continence and sexual potency by this technique, but so far no one has been able to prove this. There is NO evidence, nor even any reason to think, that it is more effective in removing the cancer. All that can be said with confidence is that the robotic approach reduces the length of hospital stays, gets patients back to work sooner, and reduces blood loss. And, because of the cost of the robot itself, the expensive disposable parts required, and the longer operating time, it significantly increases the cost of the prostatectomy. But having a robot, and offering the ability to do robotic prostatectomies, has become a big marketing issue for any major hospital, even without any proof that it is better.
External Beam Radiation Therapy (EBRT)
In this treatment, as with most radiation therapy for any cancer, a treatment machine called a linear accelerator is used to direct multiple high-energy radiation beams at the target area (the prostate, seminal vesicles, and surrounding tissues) from multiple directions. Treatments are given five days a week for about eight weeks. The treatment itself takes only a few minutes, produces no sensation at all, and produces no immediate side effects. There is no hair loss (other than possible partial loss of pubic hair), no burning, no sickness, and only some patients have fatigue. You do not become radioactive. There is no need to have someone else drive to and from treatments. The only side effects arise from the fact that the prostate is actually in contact with the bladder and the front wall of the rectum. Because the radiation beam passes through the body and out the other side, there is no way that the bladder and rectum can be entirely shielded from the radiation. Most of the technological progress in external beam treatment has been in providing relative sparing of normal tissues, particularly the rectum. But almost all men, as they progress through the weeks of treatment, will experience a gradual increase in the frequency of urination and bowel movements, some urgency symptoms, and some discomfort. For most men, even at their peak, these symptoms are more an annoyance and inconvenience than a real disability. About 90% of men find that these symptoms have disappeared by about 6-8 weeks after treatment is concluded.
The effectiveness of treatment is determined by long-term followup of the PSA level. The PSA may take a full year to fall to its ultimate level, which is usually in the range of about 1, or even less. The value is not as important, however, as the pattern. If the PSA falls to a low level, and then stays steady, with only minor variation, indefinitely, the patient is considered “cured”. The PSA will not fall to zero, however, because there is still a prostate present and small amount of PSA will be produced indefinitely.
If there are any long-term changes following EBRT, they are not likely to be urinary in nature; usually the urinary tract recovers nicely. Long-term problems, if there are any, are usually related to rectal function. Some men find that they simply have more small bowel movements than before, because their rectum is less able to accommodate a large movement. Others may have hemorrhoid symptoms that require treatment. Some men will find that they have to be very careful when passing gas, as their ability to know what is passing is impaired. Others may have painless bleeding with bowel movements, because the blood vessels in the anterior rectal wall are made more fragile by the radiation. Sometimes these problems will resolve in a few months. Sometimes they may require treatment but eventually resolve. Some men simply need to learn to live with them. Luckily, any severe long-term problems are quite rare.
Sexual function after treatment requires some explanation. During EBRT, there is no real change in sexual function, except that orgasm may have a heightened or somewhat unpleasant sensation. You are not radioactive, and you are not contagious; you cannot harm your partner so there is no reason to abstain. Over the subsequent few years, however, there is an increased risk of erectile dysfunction. Perhaps the best way to think of this is as a “premature aging” of your sexual function. Some men are not affected at all, but many men find that over the next 1-3 years they begin to need potency-enhancing drugs, such as Viagra. Of course, erectile dysfunction eventually happens to all men, so it is hard to sort out completely, but it is fair to say that a man who goes through radiation therapy is more likely to need help from drugs in the future than a man who does not. There is no apparent difference in outcome, in this regard, between EBRT and brachytherapy. Whatever it is that the radiation is doing, it seems to be about the same with either method.
Intensity-Modulated Radiation Therapy (IMRT)
Over the years, computer technology has helped to make EBRT more effective and less damaging. IMRT is the result of the ever-more-powerful computers that have come into use in the past few years, plus special linear accelerator technology. (See a more technical description here.) With intensity-modulation, it is possible to increase the radiation dose to the target area while protecting adjacent tissues (such as the rectum) that are vulnerable to radiation damage. This allows us to give a higher radiation dose to the prostate, increasing the likelihood of cure, while limiting the dose to the rectum to reduce complications.
Image-Guided Radiation Therapy (IGRT)
IMRT (above) is basically the ability to “shape” the distribution of radiation dose more precisely. If it is not aimed precisely, however, that ability is wasted. The prostate can actually move around in the body. If the bladder is full, the prostate moves downward. If the rectum is full, the prostate moves upward. Image-guided radiation therapy (IGRT) is IMRT with the additional ability to take a picture of the target area just before treatment, and to aim at the precise position of the prostate gland — right now! IGRT adds somewhat to both the time needed for treatment and the cost of the treatment. There is still no evidence that IGRT actually improves the cure rate, although it is clear that it reduces the short-term side effects and the chance of long-term complications. Most insurance plans are now authorizing IGRT as well as IMRT. (For more information on insurance, check here.) (For more information on self-interest on the part of your radiation oncologist, check here.)
Radioactive Seed Implant
The term brachytherapy comes from the Greek root brachios, meaning short, or close. In this case, it means the implantation of radioactive seeds into the prostate gland, to treat the cancer at “short range”, from within. The “seeds” are tiny stainless-steel capsules, small enough to pass through a needle. When their radioactivity is expended, after a few months, they simply sit in the prostate for the rest of your life. The radioactive isotopes used are Iodine-125, Palladium-103, and Cesium-131. At ROA we use I-125, simply because it is less expensive and easier to use. There are those who prefer Pd-103, but there is no proof that it is more effective. Cesium-131 is quite new and very expensive, and again there is no evidence that it is more effective.
Brachytherapy is very difficult to do properly when the prostate gland is larger than about 60 cubic centimeters, or if it is very broad so that the pelvic bones will interfere with placing the needles. Sometimes, if a man has a prostate that is too large but he really wants a seed implant, we give a dose of LHRH agonist to “turn off” testosterone for a few months. Often this will cause shrinkage of the prostate gland by as much as 30-40%. Symptoms from this treatment are the same as described under hormone therapy.
There are three steps to a prostate seed implant.
First, it is necessary to carefully measure the size and shape of the prostate with an ultrasound device, which is called a volume study. This is very similar to the process used for your prostate biopsy, except that there is no pain, and it takes about fifteen minutes. This information is used by our medical physicist to calculate how many seeds will be required, of what strength, and exactly where they will be placed to achieve the desired radiation dose to the prostate. The seeds are pre-loaded into needles prior to the procedure.
Second is the implant procedure itself. On the appointed day, you come to the operating room and are positioned on the table as you were for the volume study. When you are comfortable, you are anesthetized. Your radiation oncologist and the medical physicist collaborate in implanting the needles containing the radioactive seeds through the perineum (the area between the scrotum and the anus) into the prostate, under constant ultrasound guidance. When they are happy with the seed placement, your urologist does a brief exam of the urethra and bladder to be sure that there is no damage and no seeds are left in the bladder, and puts a Foley catheter into the bladder. The whole procedure takes about an hour. You wake up in the recovery room and go home a couple of hours later, with the catheter connected to a leg bag. The catheter comes out the following day; it is easy to take out yourself, or you can come in to the office.
The third step is a month later, when you return for a CT scan of the prostate to show exactly where the seeds ended up and allow us to calculate the radiation dose administered. This is primarily to allow us to continue to learn from our experience, although in theory it allows us to do a second procedure to correct an implant that is inadequate. Our experience to date is that this is necessary in 1 case of every 350.
The radiation from a brachytherapy procedure is effectively confined to the prostate. Therefore the expected side effects are urinary: frequency, urgency, and burning with urination. There are seldom any rectal or other effects. Curiously, the amount of burning is quite unpredictable. Although we aim for the same radiation dose for all patients, some have almost no burning and others have quite a lot. There are medications to relieve this if necessary, and by about two months most patients have had a major resolution of their symptoms.
Those few patients who do not have complete resolution of symptoms usually have urinary problems, rather than rectal problems, due to the localized radiation to the prostate. Sometimes the frequency and urgency will persist several months, and in rare patients things will never go back to normal. Some patients will experience injury to the urethra that may cause stricture requiring dilations in the future, and other may experience incontinence. Sometimes these problems can be corrected with further treatment, and other times they must be lived with.
Men who already have a lot of prostate-related voiding problems seem to have more such problems associated with brachytherapy, and a higher likelihood of continuing to have voiding problems in the future. For this reason, such men should probably consider options other than brachytherapy.
You will have detectable radioactivity in your body for as much as a year, but this is of such a low level that it basically presents no risk. Although you can have intercourse, we ask that you wear a condom for the first few weeks so that there is no chance of transferring a radioactive seed to your partner. For about four months, you should not have prolonged, close contact with babies, children, or pregnant women. This needs to be put into perspective. It is perfectly safe to sit next to your granddaughter during a movie, but you should not hold her on your lap where her young ovaries would be only inches from your prostate. The range of the radiation is very limited. Your radiation team will give you more specific information.
Sexual function after treatment requires some explanation. You will have no immediate effect upon sexual function except possibly a heightened or unpleasant sensation during orgasm. Over the subsequent few years, however, there is an increased risk of erectile dysfunction. Perhaps the best way to think of this is as a “premature aging” of your sexual function. Some men are not affected at all, but many men find that over the next 1-3 years they begin to need potency-enhancing drugs, such as Viagra. Of course, erectile dysfunction eventually happens to all men, so it is hard to sort out completely, but it is fair to say that a man who goes through radiation therapy is more likely to need help from drugs in the future than a man who does not. There is no apparent difference in outcome, in this regard, between EBRT and brachytherapy. Whatever it is that the radiation is doing, it seems to be about the same with either method.
High Dose Rate Brachytherapy
This is another brachytherapy technique, using only temporary implantation of the radioactive seeds. It does not mean that a higher radiation dose is given to the prostate, but rather that the radiation is deposited at a higher rate. The preliminary measurements and the operative procedures are similar to the permanent-implant brachytherapy above, but instead of implanting the seeds themselves, multiple hollow tubes are inserted into the prostate gland and left sticking out of the skin of the perineum — between the anus and the scrotum. Then the man stays in the hospital for a few days, and several times he is taken on a stretcher to a special shielded room where the tubes are attached to a special radiation machine. Controlled by a computer, this robot-like machine slides a tiny, intensely-radioactive pellet attached to a stiff wire into each of the tubes in turn, allowing it to stay for a few seconds at each of dozens of pre-programmed locations, “painting” the radiation throughout the prostate gland. These treatments are completely painless and take only a few minutes, but it is necessary for the man to stay in bed and be very careful, for several days, not to dislodge the tubes that are emerging between his legs.
The advantage is that the radiation can be very precisely controlled and distributed more evenly around the prostate, or even intensified in certain areas if desired. The disadvantage is greater time commitment and discomfort for the patient, more time and trouble for the doctor and the medical team, and greater expense. Only a few facilities in the country have much experience with this technique and continue to offer it. Many others have tried it, but still primarily do permanent seed implants. Our group is very satisfied with permanent implants.
Combined External Beam Radiation Therapy with Brachytherapy
Some radiation oncologists routinely recommend a combination of five weeks of EBRT with seed brachytherapy. We now do this only very rarely. The theory is that this approach combines the advantage of EBRT — broad coverage outside the prostate — with the advantage of brachytherapy — high radiation dose within the prostate. The fact is, however, that no one has yet proved that this approach is more effective than appropriately selected single-mode treatment. The side effects and the risk of long-term complications are definitely higher when both forms of treatment are used, and the expense is almost double. The few long-term complications that we have seen in our patients are almost all in patients who had combined treatment in the early years of our experience.
For men who have intermediate or high risk disease, we feel we can do a better job by using IGRT to treat the prostate to a high radiation dose while selectively treating the lymph nodes at risk to a moderate dose, and adding hormone suppression.
There may be a reason why combined treatment is popular, despite its hazards and cost, and the lack of favorable statistics. It is simply that it is a compromise. Urologists favor a seed implant: it is an operative procedure with which they are comfortable. Radiation oncologists tend to favor EBRT for all but the lowest-risk cases for its greater coverage of potential spread beyond the prostate. Thus the two specialties sometimes compromise on combined treatment for patients with intermediate risk cancers.
Cryotherapy is similar to high-dose-rate brachytherapy in that thin tubes are inserted into the prostate through the perineum, under anesthesia. Instead of radioactive seeds, however, supercold liquid is circulated through the tubes, freezing the prostate and destroying the cells, both normal and malignant, by disrupting their cell membranes. Great skill and care is needed to freeze the whole prostate without damaging the immediately adjacent wall of the rectum. It is also very important not to freeze the urethra, or the patient will become incontinent. Since the urethra passes through the prostate, it must be warmed even as the prostate is being frozen in a solid ball around it. This is an obvious place for problems if the freezing goes too far, or not far enough. If everything goes perfectly, the chance of cure is very good, about the same as with seed brachytherapy. The incidence of impotence is nearly 100%, however, and the chance of rectal or urethral injury is higher than with brachytherapy, even in the most experienced hands. Since there is now a 20-year track record for brachytherapy, and there is not even a theoretical advantage for cryotherapy, we see no reason to even consider it.
High-Intensity Focused Ultrasound (HIFU)
This treatment is like cryotherapy, but even less proven. High intensity sound waves, instead of freezing, are used to heat and destroy the cells in the prostate. Once again, it is unproven, hazardous, and has not even a theoretical advantage over brachytherapy, which has a 20-year track record of effectiveness and safety. We see no reason to consider it.
WHAT IS THE BEST TREATMENT?
So now we’ve surveyed the biology of prostate cancer, the risk factors in your case, and the treatment options, and it’s time to tell you what the best treatment for you is. Well, not quite yet! First, let’s talk about why it’s so hard to tell which treatment is best.
A little historical perspective.
Before about 1988, when PSA testing became available, there were basically two kinds of prostate cancers. There were early cases, where an alert internist felt a lump in the prostate on a rectal exam, and there were advanced cases, where a man came into the emergency room in the middle of the night, unable to void, and was found to have a rock-hard prostate the size of a baseball.
The advanced cases were treated with hormones and radiation therapy, and very few of them were curable. We did what we could, and we didn’t expect much.
The early cases, though, were often curable. If the patient was young and otherwise healthy, and the prostate cancer was confined to the prostate, the treatment was almost always a prostatectomy. But if the patient was elderly, or obese, or severely diabetic, or had severe heart disease or other problems, he was usually sent for radiation therapy instead of surgery. We radiation oncologists did our best.
To the surprise of no one, the patients who had surgery — and who had been chosen to have surgery because they were younger and healthier — tended to survive longer than those who had radiation! There arose a natural perception that surgery cured prostate cancer better than radiation did. But there were reports from places like Stanford that gave tantalizingly good results when the early, healthy patients were, for whatever reason, treated with radiation therapy. There were even early trials of seed brachytherapy, but via an operative technique where the surgeon opened up the patient’s abdomen and the radiation oncologist tried to implant the prostate with seeds, with rudimentary tools, no computer assistance, and not a great deal of success.
In 1987, PSA was discovered and the prostate world changed forever. At about the same time, Dr. Gleason formalized his histologic grading system. Suddenly there was a flood of younger, healthier men who were discovered to have a rising PSA and, on biopsy, a low risk prostate cancer. Many of these young men were not eager to lose sexual function, and wanted to explore other options like radiation therapy.
At about the same time, computer technology was advancing and ultrasound equipment capable of imaging the prostate was becoming affordable. Several groups, most notably in Seattle, began systematically doing transperineal seed brachytherapy in the way that it is done today. Other groups, using computer power to do 3-D CRT, began increasing the radiation dose to the prostate while restricting the dose to the rectum. Both techniques proved highly effective against early stage disease.
Advanced disease was still a problem, though. Even if a man did not have prostate cancer spread to the bones, it was hard to control a large prostate tumor with a tolerable dose of radiation. Several prospective, randomized trials proved that the simultaneous treatment with hormone suppression (LHRH agonist, chemical castration) and radiation could dramatically increase the survival rate in advanced disease. This has since been extended to intermediate-risk disease, with favorable but less remarkable results.
Please see the sidebar on prospective, randomized trials for more on why there are no good statistics on early prostate cancer and little chance of getting any better ones. This is not a paper on statistics, and I am not a statistician, but it doesn’t take a genius to see the problem. The term “bias”, as used by statisticians, does not imply any dishonesty or malfeasance, but simply a source of error that will tend to push statistical results in a predictable direction, or perhaps even an unpredictable direction.
Selection bias. This was alluded to above in talking about why some patients got surgery and others radiation. If two groups of patients start off with different ages and health status, one expects them to have different long-term survival. When a man first learns that he has prostate cancer, he usually learns it from a urologist. A urologist is a surgeon, who usually enjoys doing radical prostatectomies. If the patient is thin and healthy and has early-stage disease, the urologist is going to be inclined to recommend surgery. If the man is old or sick or has late-stage disease, he is likely to be referred to a radiation oncologist. Even if the urologist assiduously refers all of his patients for a radiation therapy consultation — as many of them do — it is still almost certain that the average surgery patient will be younger and healthier than the average radiation patient, and accordingly can be expected to live longer, regardless of the treatment chosen. Young people live longer than old people!
Upstaging bias. Suppose that we were doing a research project using 300 men with low-risk, stage T1C prostate cancer. We randomly assign 100 men to have radical prostatectomy, 100 to have EBRT, and 100 to have brachytherapy. We want to see which treatment is more effective. Suppose further that, although we don’t know it yet, the three treatments are absolutely equal in cure rate. If the treatments are equal, when a few years have gone by and we assess the survival results, we should expect the three groups to have equal survival. In practice, though, the results usually favor surgery, because of what is called upstaging bias.
All 300 men would have been assigned a clinical stage of T1C. “Clinical stage” is the extent of disease revealed by digital rectal exam (DRE), ultrasound exam, and scans, but prior to any surgery other than the initial biopsy. For the 200 radiation patients, there will never be any more information available on the extent of disease, because they will have no more surgery, and so their survival results will be reported as men with stage T1C disease. The 100 surgery patients, however, will have their prostates removed and examined by the pathologist. At least some of them will be found to have a higher surgical stage than T1C, because they will have disease that has spread outside the prostate. A reasonable expectation is that 25 men in each group of 100 will have unexpected extension out of the prostate (T3) and 5 will cancer spread to the lymph nodes (N1). Thus, only 70 of the 100 surgical patients will be reported as having stage T1C disease, and those will be the most favorable men in the group.
An unwary statistician, analyzing the results, would find himself comparing 100 men in each radiation group with the 70 most favorable men in the surgical group. Since the men with more advanced disease have been removed from the surgical group but are still included in the radiation groups, surgery will appear to be more successful.
What about the 30 men who were found at surgery to have T3 or N1 disease? Suppose we compared their survival with 30 other men (outside our study) with clinical stage T3 or N1 disease who had been, appropriately, treated with radiation therapy. Once again, the patients treated with surgery have better survival! Although the surgical patients had T3 or N1 disease, the extent of that spread outside the prostate was so minimal that it was recognized only after it was removed. It is unfair to compare them with the radiation patients, who had much more extensive disease, detectable by DRE, ultrasound, or scan. Even within a stage group, men with minimal disease are going to have a better chance of cure than men with extensive disease.
Interestingly, even though each man’s treatment was randomly assigned, this upstaging bias made surgery look better than radiation for the early stage patients, and also made surgery look better than radiation for the advanced patients! Yet there was no real difference between the effectiveness of surgery and radiation, as we posited in the first paragraph.
In a genuine randomized prospective clinical trial, the statistician would compare the entire surgical group, including the unfavorable patients, with the two radiation groups, each of which contains an equal number of (unidentified) unfavorable patients, and would find that survival was equal among the three groups. Unfortunately, such a study has never been done, and is unlikely ever to be done. When comparing results between institutions, or even between nonrandom treatment groups in a single institution, upstaging bias will always tend to make surgery look better.
Salvage treatment. We often hear a patient quote his urologist as having said something like this:
“It’s true that radiation and surgery are equally effective for your low-risk prostate cancer, but if you have surgery first and you later need radiation, it can still be given. If you have radiation first, you can never have surgery.”
This statement is pretty much true, since it is very difficult and hazardous to try to do a prostatectomy after radiation. This idea often leads people to conclude that it’s therefore better to have surgery first, in order to preserve another option in case it’s necessary. But think a little farther. If it’s true that the treatments are equally effective — and it does appear to be true! — then what that really means is that whichever treatment you choose — whichever path you take – your chance of being alive and free of cancer ten years later is the same.
Again let’s consider 300 men with identical, low risk prostate cancers with a 90% chance of cure. One hundred men decide to have a radical prostatectomy, 100 have EBRT, and 100 have seed brachytherapy. Since the treatments are equally effective, when we come back ten years later we’ll expect to have 90 men in each group who are cured. In each of the radiation therapy groups, the initial treatment cured 90 out of 100 of the patients; none of them had subsequent surgery. In the surgery group, the initial treatment cured somewhat less than 90 — perhaps only 80 — of the 100 men. The other 10 men were able to be cured by radiation when the surgery was not completely effective. In this example, surgery alone was actually less effective than radiation therapy alone. But surgery, with radiation as a fallback in case it doesn’t work, is as effective as radiation alone! The numbers we used in this example are simply an example. This is not an attempt to prove that radiation is better than surgery in low-risk patients, because it’s not true! But neither is it true that it’s better to start with surgery than with radiation. The outcomes are equal!
In the medical literature, it is usually not possible to tell whether the surgical survival figures include those patients salvaged by radiation. The few papers including that information generally admit that their criterion is whether the patient is ultimately cured, with or without the addition of radiation — which is what really counts — rather than whether the patient is cured by surgery alone.
Doctor preference. Urologists choose to be urologists because, during medical school, they discovered that they liked to do what it is that urologists do. Then they were educated, trained, coached and mentored by other urologists, and they tend to talk frequently with still more urologists. Small wonder that they tend to favor a urological solution to low-risk prostate cancer, especially when there is no convincing evidence that there is any better alternative. For exactly the same reasons, most radiation oncologists will tend to favor radiation treatment for the same low-risk patient. The best and most honest doctors in both fields will recognize this bias and will strongly recommend, or even insist, that their patients get opinions from specialists in both fields before making a decision. It is a fact, though, that the urologist almost always talks to the patient first. A patient who simply wants to get on with treatment, or who wants his doctor to make decisions for him, will more often end up with surgery than with radiation therapy. Click the link at the head of this paragraph for a fascinating glimpse of how different groups of doctors can differ in how they view the very same cases.
Doctor investment and potential conflict of interest. There are two kinds of medical charges. If you have an operation, for instance, the doctor will submit a bill for professional services and the hospital will bill for technical services. Things get muddy, however, if the doctor also owns the building or the expensive equipment, and thus also bills for the technical charge. Now the doctor is not just “selling” you his time and experience as a professional. He is also “renting” you his investment in that building or equipment. He has his own money at risk for that investment, and he needs to pay those bills whether or not the equipment is used. There is an obvious incentive to be sure that the equipment is used so that it generates money to pay for itself, and make a profit. This happens in radiation oncology if a group of radiation oncologists owns the facility and the equipment with which you are getting treated. It can happen in urology if a group of urologists owns the surgical center, or perhaps the robotic machine used for prostatectomy. A new development in the past few years is that some groups of urologists actually own a radiation therapy center and employ a radiation oncologist. The radiation oncologist bills for professional services, but the much larger charge for technical services goes to the urologists who own the business. These arrangements are not illegal, but they may provide situations where the incentives of the doctors are not entirely coincident with the best interests of the patient. ROA does not participate in any arrangements of this kind. It is perfectly acceptable to ask your doctors — in the case of prostate treatment or any other treatment — whether they have an ownership interest in the equipment and facilities that they use, and whether this affects their decisions in your care.
Simple expediency.. The “deferred intervention” option is almost certainly under-used in American medicine. Nobody likes the feeling that he has cancer and is doing nothing about it. For a doctor, it is usually easier to recommend treatment to a prostate cancer patient than it is to recommend no treatment, or deferred treatment. The discussions can sometimes be long and frustrating. In addition, doctors are worried that, if they recommend against treatment but the disease progresses, they might be considered to have been negligent. If they recommend treatment that is not strictly necessary, they will not be faulted when the patient does well in the long run, and in fact may be able to take credit for having “cured” a patient who doesn’t need curing! Even if the patient is harmed somewhat by the effects of the treatment, this is within the range of expectations, and the doctor will not be faulted. The outcome of all this is that a great many men who do not really need treatment will get treated anyway.
Summary on statistics. After all of this, it is worth reiterating that there is simply no statistical information available to show, for low-risk prostate cancer, that any one treatment is better than another. The leading experts in this country, in urology, radiation oncology, and medical oncology feel that the three main options — radical prostatectomy, external beam radiation, and seed brachytherapy — are completely equivalent in effectiveness, or at least are so close in effectiveness that there is no good reason to choose one over the other. There are large national studies on effectiveness and on functional outcomes to bear this out. Click on these links if you want to learn more.
TREATMENT OPTIONS BY RISK GROUP
Some men do not need treatment at all. Discuss this with your doctors and decide whether “deferred intervention” is the right choice for you. There is a good article, and accompanying editorial, in the December 1, 2010 issue of JAMA, the Journal of the American Medical Association. You can’t access it online without a subscription, but the medical librarian at most hospitals will eagerly help you get a copy.
Men in the low risk group have a low risk of cancer spread outside the prostate gland. Therefore, any treatment that adequately removes, or kills, the cancer cells will prove to be effective. No treatment is 100% effective, because even in this low-risk group there are some men whose cancer has already escaped through the bloodstream to take up residence elsewhere, usually in the bones. If even a few cells have escaped, although they may be undetectable by any method, eventually they will declare themselves. But all the men in this group will have a dramatic drop in their PSA with treatment, and in about 90% of these men, prostate cancer will never again be an issue in their life.
If you are going to be treated for low-risk prostate cancer, in my opinion, the three best choices are (in no particular order):
Radical prostatectomy, by whatever method your urologist feels is best for you. External beam radiation therapy with IMRT or IGRT. Prostate seed brachytherapy.
All of these offer an identical chance of cure, so the best way to choose among them is to select the option with a spectrum of inconvenience, discomfort, risk, and long-term effects that is most acceptable to you. This is not a scientific choice, but an emotional and practical one. Read again about these issues in the materials above, and follow the links to still more information. Spend most of your time with your urologist and your radiation oncologist in discussing these factors. When you have made the decision that feels right to you, don’t second-guess yourself. There is no “right” answer; only the right answer for you.
For a chart of the side effects and risks involved in the choices for low-risk cancer, check here.
Men with high-risk disease, unless they have a very limited life expectancy, should have treatment. High-risk disease can advance rapidly and pose a threat even to an elderly man. There is a very high chance that disease has escaped from the prostate gland, and therefore neither radical prostatectomy nor seed brachytherapy is likely to work. It is easy to address the cancer that is still within the gland, but it is the cancer that has escaped that poses the real threat. The best treatment for high risk disease, in my opinion, is:
Hormone blockade combined with external beam radiation therapy.
External beam radiation can address not only the cancer within the gland but the cancer that may have spread to the seminal vesicles, the bladder base, the adjacent lymph nodes, and the soft tissues surrounding the prostate. There is good evidence that radiation therapy is more effective, and produces a higher cure rate, when it is combined with suppression of male hormone production before, during, and after the radiation.
The usual schedule is:
Months 1-2: LHRH agonist injection (leuprolide 30mg or equivalent) lasts four months with bicalutamide (Casodex) 50mg daily by mouth for the first four weeks.
Months 3-4: Radiation therapy daily, 5 days per week, for a total of 40-45 treatments. LHRH agonist is still working.
Months 5-24: LHRH agonist injections, every four months, for two years.
The schedule need not be rigid. During the 8 weeks of radiation you should not plan to travel, but the time for radiation does not have to be exactly during months 3-4 as above. If you have travel plans or obligations that you would prefer not to change, the radiation treatment can be pushed back a few months with no reduction in effectiveness. Once the injection of LHRH drug has been given, the treatment has started. The initial hormone suppression is not a delay in treatment, but an important component of the treatment.
In the low-risk group, there are three good treatments. In the high-risk group, most people agree that there is only one best treatment, as explained above. The intermediate group is where things get confusing. In general, these men have a risk of spread outside the prostate that is higher than the low-risk group. Neither prostatectomy nor seed brachytherapy can address spread outside the gland as well as external beam irradiation can. As a radiation oncologist, I immediately start to think about EBRT.
But not all intermediate-risk cases have the same kind of risk. In this group, it’s best to look closely at just why a particular case qualifies as intermediate, to see whether that gives a clue to what treatment might be appropriate. Here are a few examples:
A man has PSA 6, stage T1C, and three out of twelve biopsies were positive. One biopsy was Gleason 3+4, but the others were Gleason 3+3, and none of the biopsies showed a great deal of cancer. Although the presence of some Gleason 7 disease qualifies as intermediate risk, I would consider this man to have pretty much the same treatment options as a low-risk case.
A man has T1C, PSA 11, and a large prostate with 6 of 12 cores positive for Gleason 3+3 cancer. His PSA last year was 9.5 but biopsies at that time did not show cancer. The fact that his PSA is over 10 puts him into the intermediate group, but he does not have a very rapid rise in PSA. He had only Gleason 3+3 cancer found, so his risk of spread is less than if he had a component of Gleason 4. The fact that he has a large prostate, containing what seems to be a fairly large amount of cancer, implies that perhaps intensive treatment of the prostate itself, by prostatectomy or brachytherapy, might be a good choice.
A man has A PSA that rose from 4 last year to 8 this year. He has no palpable lump so his stage is T1C, but almost every biopsy from his prostate showed large amounts of Gleason 4+3 cancer. Although he technically fits into the intermediate-risk group, the large amount of disease and the fast rise in PSA are very worrisome. I would treat him as I would treat a man in the high-risk group.
Although I don’t often use MRI staging for prostate cancer, I do use it if I’m considering surgery or brachytherapy for a man with intermediate risk. The MRI exam is long and uncomfortable, and not perfect in assessing the extent of disease, but if it shows cancer escaping the prostate it is almost always correct. Such a finding would reclassify the man as high risk, and lead me to recommend EBRT with hormones.
When we do treat men in the intermediate-risk group with EBRT, there is a question as to whether to add hormone suppression. In high-risk men, the benefit is clear, and statistically proven. In the intermediate group, the benefit is smaller and not as clear. At present, the usual practice among radiation oncologists is a compromise: we add only a short course of hormone suppression, often just a single dose of LHRH agonist to suppress testosterone production for two months prior to radiation and during the radiation itself. This short course is still troublesome for many men, but is much less likely to lead to any long-term hormonal problems and more likely to allow for recovery of sexual function.
FOLLOW-UP CARE AND PSA MONITORING
Prostate cancer is almost unique among human cancers, in having a very specific and sensitive, simple blood test for followup. There is no such thing as a blood test that proves that you’re cured, but a PSA that drops after treatment and stays low for the rest of your life is the next best thing. In almost every case, a check of the PSA every six months is all that is necessary.
Whether you have a prostatectomy, EBRT, or brachytherapy, your PSA will fall after treatment. There is no doubt at all that almost all of your prostate cancer has been removed or killed. The question is whether the very last cancer cell is gone — and there is no test for that except the test of time. Your PSA needs to be followed.
After a prostatectomy, there should be no prostate cells left in the body, and therefore no source of PSA. The PSA level falls quickly, within a couple of months, to a level that is undetectable, generally considered as less than 0.01. Any detectable PSA after prostatectomy is a reason to be evaluated for further treatment.
After radiation therapy by either method, there is still a prostate gland present, so there will still be normal prostate cells that are a source of some PSA. The PSA level falls more slowly, taking perhaps six months after brachytherapy and up to a year after EBRT to reach its lowest level, and it does not fall to undetectable levels. Of course, it is gratifying when this is as low as possible, often under 1.0, but the absolute value is much less important than the pattern. If the PSA falls to a low value and stays there forever, we don’t care what the number is.
PSA, as you already know, is only made by prostate cells. But prostate cancer cells, even if they have traveled to other parts of the body, are still prostate cells, and they will still make PSA. Therefore, watching the PSA allows us to watch for any cells that may persist in the prostate area as well as for any cells that may have metastasized. The PSA level alone cannot tell the difference, however. A rise in PSA may signal local disease recurrence, metastatic disease, or both, and signals a need for a re-evaluation.
The PSA is such a sensitive early-warning-system for any recurrence of disease prostate cancer that no other testing is necessary. Bone scans, repeat biopsies, and other tests are going to show nothing useful if the PSA is low and stable. The only exception is with a very few high-risk men who usually have Gleason scores of 5+4 or 5+5 and a low PSA at the time of diagnosis. These men seem to have cancer cells that have lost the ability to make PSA. They need special attention to followup, beyond the scope of this discussion.
Do you sometimes treat only a part of the prostate gland?
In many other cancers — breast cancer, lung cancer, and colon cancer, for instance — we remove just the tumor, rather than the whole organ. In prostate cancer, we generally treat the gland as a whole, for two reasons. First, the prostate gland doesn’t do anything particularly useful. It produces seminal fluid, so any man who has had prostate cancer treatment will produce very little ejaculate, but this is not a problem since it’s rare that a man of prostate cancer age is concerned about becoming a father! Second, it’s not really possible to know exactly where the cancer is within the gland. We get some information from the biopsies, and we can get more information from an MRI scan if we need to, but we can’t be sure. We know from experience that it’s common to operate on a man who seems to have cancer only on one side of the gland, and learn from the pathologist that cancer was actually present on both sides.
If we had the ability to know exactly where the cancer is, within the prostate, it might be possible in some cases to leave a portion of the gland in place, thereby avoiding trauma to the neurovascular bundle along the surface of the gland on that side, and improving the maintenance of potency.
Some doctors are already using IMRT, or placing a few extra seeds with brachytherapy, to give more radiation to a detectable lump of cancer within the prostate. This is always done in addition to an overall curative dose to the entire gland, however.
What happens to the prostate after radiation therapy?
Luckily, malignant cells are usually more sensitive to radiation damage than normal cells. Part of this may be due to the fact that malignant cells are mutants, but certainly much of the difference is due to the fact that cells undergoing mitosis (cell division) are more susceptible to radiation damage than cells that are simply performing their normal functions. Since cancer cells reproduce more rapidly than normal cells, they are more likely to be undergoing mitosis when the radiation is given, and more likely to be killed by it. The normal cells in any gland, however, also reproduce, so many of them are killed as well. In treating prostate cancer with radiation, we expect to kill all of the cancer cells, and many of the normal glandular cells as well.
When we say that a cell is killed by radiation, we don’t mean that it is physically destroyed. We consider it to be “killed” if it is damaged so that it can no longer reproduce, in the same sense that a cat becomes a biological “dead end” if it is neutered. It may continue to be a cat for many years, but will not produce any more cats! A cancer cell that cannot reproduce is no longer a danger, and it doesn’t matter if it exists a few more weeks or months. Eventually it will get old enough that it must either reproduce or die, and then it will really die and fall apart. Your body has been cleaning up dead cells all your life, of course, so the dead material is just absorbed and recycled, and any damage is repaired or becomes a scar.
What does this mean in the prostate? First, it means that the cancer cells will continue to make PSA for a time. It may take a year or more for the PSA to fall as far as it is going to, and the PSA seldom falls to zero, since there are still some normal cells making PSA. The number of normal cells that survive is small, however, so usually the PSA will fall to a low level. The exact level isn’t important; what is important is that it stays low and doesn’t show any rising trend in the future. Second, since the prostate gland is the source of seminal fluid, it means that the volume of ejaculate will be much less after radiation therapy, as well as after surgery.
What does the prostate gland actually look like? Usually it shrinks, slowly, as the glandular cells die. When a large amount of cancer was present, the shrinkage can be quite dramatic. A biopsy of a previously-treated prostate gland looks damaged under the microscope. Think of it sort of like the forest after a fire has gone through: there are still blood vessels and connective tissue and ducts and remnants of glands, but not the lush activity of a healthy gland. After radiation therapy, symptoms of benign prostatic hypertrophy are likely to abate somewhat, and further BPH is very unlikely.
What is the CyberKnife©, and how is it different?
The CyberKnife (CK) has a catchy name and great marketing that sometimes makes it a bit difficult to understand just what it is, what’s different about it, and how it is used to treat prostate cancer. Let’s de-mystify a bit.
The heart of the CK is a linear accelerator that makes a beam of high-energy x-rays, just like every other radiation therapy machine (except outdated cobalt units and huge proton beam facilities). What’s different is that, instead of being mounted on a rotating “gantry”, it is mounted on a computer-controlled robotic arm. If you’ve ever seen the computer-controlled welding robots in an industrial plant, you’ve seen the same technology. When the CK was first developed, the idea of a computer controlling a medical treatment device was revolutionary. Since then, however, computers have come a long way, and the computer controls in later treatment systems, such as Trilogy/RapidArc (TRA) and TomoTherapy (TT) are even more advanced and more flexible than those of the CK.
The radiation beam of the CK is capable of being aimed very precisely — but so is the beam of those other technologies. Of course, it’s not whether you can shoot straight that counts, but whether you know what and where the target is, and can hit it every time. If you’ve read this far, you already understand that 1) the prostate can move around in the body, depending on whether the rectum and bladder are empty or full, and 2) in prostate cancer we are never completely sure whether there might be some spread of cancer outside the prostate.
How does the CK deal with these problems?
The problem of prostate motion is managed just as with newer radiation therapy: with image guidance. Just before the treatment is begun, the treatment system produces an image of where the prostate is actually located at that time, and adjusts the aim accordingly. The CK technology requires implanting several metal (usually gold) pellets into the prostate gland — a minor surgical procedure — in preparation for the series of treatments. Then, just before each treatment starts, two x-ray images are taken of the pelvis, at right angles. The treatment system compares the location of the pellets to their expected location, and adjusts the system until the pellets are where they are supposed to be before starting the radiation treatment. (With TRA and TT, there is no need for an operation to implant pellets, since the treatment unit itself can take a 3-dimensional CT scan that shows the whole prostate and its position with regard to the bladder and rectum.)
Users of the CK make much of the fact that their 2-dimensional localizing system can be used repeatedly during the treatment (which is not possible with the TRA or TT technologies) to guard against movement of the prostate during the treatment. This is important in the CK, because a CK treatment takes more than an hour, compared to about 5 minutes with the newer technologies. The change of a significant movement of the prostate during such a brief treatment is very small.
The problem of whether cancer cells have escaped the prostate is dealt with by the CK in the same way as it is dealt with by brachytherapy and, for that matter, surgery. CK treatments are directed only at the prostate, with no intention of treating any adjacent tissue where cancer cells might have spread. As a result CK treatment, like brachytherapy and prostatectomy, is suitable ONLY for low-risk patients.
The other big claim of the CK is that it can treat (low-risk!) prostate cancer in only five daily treatments, rather than about 40 treatments for TRA or TT. This is done by giving much more radiation with each treatment: 7.25Gy five times, instead of 2Gy forty times. Larger radiaton doses kill cells in a non-linear fashion, so these two treatment schemes are calculated to do approximately the same amount of biological damage to the tumor cells and the surrounding normal cells even though their numerical doses differ. The problem is that this is still experimental. Doctors don’t know for certain, whether this formula will be, in the long run, as effective in killing the cancer cells and as safe for the normal cells. So far, a few hundred men have been treated in this way, and some have been followed as much as four or five years, but in prostate cancer we need to look at longer-term data to decide whether the treatment is both safe and effective.
This is good, valid medical research, and there are some good reasons from radiation biology to think that it will be successful. So far, the men treated in this way seem to be doing well. Many universities and medical research groups are doing similar studies, using not only CyberKnife but other modern IGRT technologies such as TRA and TT. Unfortunately, though, some CK programs are not doing this as a scientific program, but rather marketing the technology as if it were proven, or treating men who do not understand that the treatment is experimental, or who do not have low-risk cancers.
If we eventually prove that five large treatments are safe and effective for early-stage prostate cancer, it will likely become the preferred treatment. It will probably not be done much on the CK at that point, since on newer IGRT equipment each treatment will take about ten minutes instead of more than an hour, and will cost hundreds of dollars instead of thousands.
Which prostate treatment is the “easiest”?
While it’s hard to take a position that any particular treatment is the best, I think it’s pretty clear which is the easiest: external radiation with IGRT. The worst part about it is the inconvenience of eight weeks of treatments. The IMRT/IGRT technology has reduced the dose to the bladder and rectum dramatically. You’ll have some problems with frequent trips to the bathroom, and getting up at night, but in most cases there is no serious discomfort. There is little chance of any real disability; many men go through a course of treatment without missing a day of work, or even telling the people at the office.
What do you think of the MSKCC prostate cancer prediction tool?
I don’t like it. It leads people to think the decision-making in prostate cancer can be boiled down to just a simple number, which isn’t the case. And the survival numbers that come from its calculations frankly confuse me. Even when I use the references that they list as the source of their information, I can’t make sense of their numbers. For instance, when I enter a 70-year-old man with a PSA of 20, a Gleason score of 5+5=10, 8 positive biopsy cores and cancer invading the seminal vesicles (T3B), it calculates that the man will have a 47% chance of being free of cancer progression, 5 years after a radical prostatectomy. That just doesn’t make sense in my experience. I don’t even know a surgeon who would operate on such a man!
If you do choose to use the MSKCC tool, please also read the “frequently-asked questions” on that website. The link is just above the dark blue bar at the top. Question 4 is probably the most important: it clarifies that the data they use are subject to all of the statistical biases explained here under “What is the Best Treatment?” and provides some valuable information about the difference between “cure” and “progression-free survival.”
Let me restate what I think is the best approach to making prostate cancer decisions:
In LOW RISK prostate cancer, when the disease is most likely confined to the prostate gland, the chance of cure is excellent with ANY effective local treatment: prostatectomy, seed brachytherapy, or external radiation therapy. Perhaps the 5-treatment approach, too, when we have more data and more time to evaluate its safety and effectiveness. And don’t forget that many men can just monitor their low-risk prostate cancer, live out their lives, and never require prostate treatment.
In HIGH RISK prostate cancer, when the chance is high that cancer has already escaped the prostate gland, a combination of hormone therapy and external irradiation of the prostate and surrounding areas at risk makes more sense.
In INTERMEDIATE RISK disease, the decision is harder to make. Find a urologist and a radiation oncologist that you trust, and spend plenty of time discussing with them the specifics of your case and the treatment options that would be most appropriate to your problem.
© 2011 Glenn L. Tonnesen