Radiation therapy in the spotlight (Part 1 of 2)

Nancy Ferrari

Senior editor, Harvard Health

Just saying the word “radiation” conjures up fears of cancer-causing agents and images of Hiroshima at the end of World War II. Adding the word “therapy” after “radiation” often fails to ease concerns. The fact that we can’t see it, feel it, smell it, or taste it simply adds to its mystique. But radiation therapy has proven its ability to trump cancer and prolong the lives of millions of patients. And thanks to technological innovations in the last several years, radiation therapy more accurately targets — and more effectively treats — tumors than in decades past.

When physicians talk about radiation, they’re referring to ionizing radiation, which is in the same part of the electromagnetic spectrum as x-rays and gamma rays. Radiation therapy devices deliver targeted doses of radiation to specific spots. It kills its “prey” by damaging the DNA in cancer cells. When the DNA is damaged, the cells can’t replicate successfully and the cancer is halted.

Among the challenges for physicians and prostate cancer patients considering radiation therapy: which type is best? There are two broad categories of radiation therapy — external beam and brachytherapy. Within each category, there are various methods and devices to deliver the radiation. Many physicians have trouble sorting out the pros and cons of each; for an anxious patient with little medical knowledge, the task proves even more daunting.

To help prostate cancer patients better understand what radiation therapy is (and is not) as well as the various delivery methods, or treatment modalities, three experts from Harvard Medical School met to discuss the topic. The panel included these physicians:

  • Irving Kaplan, M.D., an assistant professor of radiation oncology at Harvard Medical School and a radiation oncologist at Beth Israel Deaconess Medical Center in Boston. He has published extensively on various topics related to prostate cancer.
  • Carolyn Lamb, M.D., an instructor in radiology at Harvard Medical School and a radiation oncologist at Mount Auburn Hospital in Cambridge, Mass. She is a member of the American Society for Therapeutic Radiology and Oncology and has published a number of scientific papers on prostate cancer treatment, including the implantation of radioactive seeds.
  • Anthony L. Zietman, M.D., a professor of radiation oncology at Harvard Medical School and a radiation oncologist at Massachusetts General Hospital. He has spent his entire career treating and studying genitourinary tumors, particularly prostate cancer. He has authored over 100 articles on the role of active surveillance in managing the disease, as well as the use of androgen deprivation with radiation and high-dose-rate radiation.

The trio talked about the many options, recent advances in radiation therapy, and possible side effects of treatment. They also discussed eight different methods of delivering radiation; some of them are readily available and some aren’t. One method is rarely used anymore, if at all. Brief explanations of each follow. For a comparison of treatment times, advantages and disadvantages, and other considerations, see Table 1 at the end of this article.

External beam radiation therapy

External beam radiation therapy involves a series of daily treatments that accurately deliver radiation to the tumor from outside of the body (see Figure 1 below). It’s like getting an x-ray, but for a longer period of time. External beam radiation therapy effectively destroys cancer cells, but it can also damage healthy tissues nearby. To limit the collateral damage, a specialist maps out the exact location of your prostate using imaging technologies like CT scanning or magnetic resonance imaging. During treatment sessions, you may lie inside an immobilization device to prevent any movement. Several types of external beam radiation therapy exist:

  • Three-dimensional conformal radiation therapy (3D-CRT). Before treatment, three-dimensional pictures of your prostate are taken to pinpoint the prostate and surrounding structures. Using computer software, radiation oncologists and physicists determine the angles at which the beams of radiation should enter the tissue. In this way, the radiation field “conforms” to the shape of the area to be treated and helps keep radiation away from the bladder and rectum.
  • Intensity-modulated radiation therapy (IMRT) is a form of 3D-CRT that allows doctors to change the intensity of the radiation within each of the radiation beams — increasing the radiation to the prostate while reducing radiation to normal tissues. Like all forms of 3D-CRT, IMRT involves imaging studies and three-dimensional mapping prior to treatment. Because treatment conforms so tightly to the prostate, daily tracking of its location is a must.
  • Proton beam therapy uses beams of protons instead of x-rays to treat cancer cells. Proton therapy exhibits the same precision as IMRT, but it uses a different kind of radiation.
  • CyberKnife uses image guidance and computer-controlled robotics to deliver multiple beams of radiation to the tumor from almost any direction. The system tracks the tumor’s position, detects prostate movement, and automatically adjusts the delivery of radiation, if necessary, to account for any change.
  • TomoTherapy incorporates software for treatment planning with a CT scanner and the radiation delivery device into a single machine. With its circular shape, the machine can deliver radiation therapy continuously from any angle around the patient. Individual beams can also be divided into smaller “beamlets” to conform to the tumor’s contours.
  • Neutron therapy uses neutrons instead of x-rays. A few decades ago, neutron therapy showed promise, and some studies found a statistically significant improvement in five-year disease-free survival over conventional techniques. However, it didn’t seem to prolong survival, and the complication rate was far higher than for other techniques. Today, only a few neutron facilities exist, mainly in Europe, and they are not used for the treatment of prostate cancer.

Figure 1: External beam radiation

External beam radiation

During external beam radiation for prostate cancer, a patient will typically wear a gown or sweat pants that can easily be removed so that the area to be treated can be aligned with a ray of light that matches the path of the radiation. The radiation beam itself is not visible. Marks on the skin or metallic gold implants (called gold fiducials) in the prostate help pinpoint the gland’s location. The patient may also lie in a custom-made body “cast,” to immobilize the pelvis. Depending on the device used to deliver the radiation, each treatment takes about 15 to 20 minutes.

Brachytherapy

Rather than delivering radiation from an external source, brachytherapy delivers radiation, usually in the form of radioactive seeds or pellets, from a source placed inside the body. As a result, it’s sometimes called internal radiation therapy or interstitial radiation therapy. (“Brachy” comes from the Greek for “short,” meaning that the radiation doesn’t travel very far.) Brachytherapy may be either permanent or temporary:

  • Permanent brachytherapy, also called seed implantation, involves placing 60 to 100 radioactive seeds or pellets (depending on the size of the prostate gland) in or near the prostate tumor (see Figure 2 below). The seeds, which are smaller than grains of rice, are left in the prostate permanently and spare, if possible, the bladder and rectum. Over several months, the radioactivity level gradually dwindles to nothing.
  • High-dose-rate temporary brachytherapy uses needles and catheters (thick plastic tubing) to insert radioactive material into the prostate. Given the high intensity of the material, it cannot be left in the body for long. After a set period of time, a remote-controlled machine pulls the material out. The process may be repeated several times in one day or over multiple days. Catheters are removed after the final treatment.

Figure 2: Brachytherapy

Brachytherapy

Most radiation oncologists use 3D treatment planning and a template guide to precisely implant radioactive seeds and to ensure that radiation is distributed evenly throughout the prostate. Ultrasound, delivered through an ultrasound probe, or transducer, allows them to view the prostate throughout the procedure.

An overview of radiation therapy

How does radiation therapy kill cancer? Why doesn’t it destroy normal tissue?

KAPLAN: It damages the DNA in cancer cells. When the DNA is damaged, the cells can’t replicate successfully.

LAMB: Radiation affects tumor cells more than normal tissue because normal tissue does a better job at repairing damage before the DNA sustains a fatal injury. Tumor cells also get more “hits,” because their DNA is more active. That makes them more susceptible to injury.

So, the DNA in tumor cells and normal cells is different, and that’s what accounts for the different effects of radiation on tumor cells versus normal cells?

LAMB: It’s not just the DNA. It’s the whole cell and the cell’s ability to repair itself.

If a patient has radiation for some small areas of cancer within normal prostate tissue, is the entire prostate gland irradiated?

KAPLAN: Yes. The reason why is that prostate cancer is almost always developing in multiple areas of the gland at any one time. Even though a biopsy may show cancer only in a small portion of the prostate, there may be cancer that wasn’t picked up on the biopsy. Or, there could be precancerous changes in other parts of the gland. You don’t want to treat just part of the gland, because you really only have one opportunity to treat the entire thing.

Then why does it take seven or eight weeks of radiation to effectively treat prostate cancer?

LAMB: Well, if you’re trying to make use of the fact that the normal tissues do a better job of repairing themselves, you have to give them time to do that in between doses. Over years and years of treating patients and doing research, we’ve learned that a small daily dose is better than a high total dose because it can control the tumor and allow normal tissues to repair themselves.

There are debates within the prostate cancer community about whether slightly bigger daily doses would be even more effective. The theory is that because prostate cancer grows slower than other cancers it might be more effectively controlled with a larger daily dose. But this needs more study.

What are the different types of radiation?

KAPLAN: I think the thing to understand is that radiation is radiation. When we talk about different types of radiation, we’re really talking about different ways of delivering radiation to the target tissue. Put more simply, it doesn’t matter if you take the train, drive, or fly from Boston to New York. All three methods can get you there.

ZIETMAN: There are two ways to get radiation to the prostate: you either shine it in or stick it in. Shining it in from the outside is external beam radiation. The other way is to put the radiation inside the body — that’s brachytherapy.

Seeing the target

How do you visualize the target? How do you know where the prostate is and whether its position has changed from one day to the next?

KAPLAN: First, you have to understand that for most prostate cancer, we have to treat less and less volume of normal tissue. Reducing the amount of normal tissue that’s affected by radiation has made a huge difference in side effects.

ZIETMAN: One of the things we’ve learned over recent years is that with early detection we no longer have to go after lymph nodes in far-flung areas of the pelvis. We can just treat the prostate because the likelihood of finding cancer in the lymph nodes is so low.

LAMB: But in a high-risk patient, it would be a different story.

ZIETMAN: It might be a different story.

The second thing we’ve learned is that if we are to eradicate the cancer in the prostate, we need relatively high doses of radiation to get the job done. But we need to be careful. Even though we’re treating less normal tissue in terms of volume, we can still damage it because we are using higher doses of radiation. All of the technologies that have been developed are geared toward focusing the radiation where it’s needed to allow higher doses to be given and minimizing the dose to normal tissue. And they all employ contemporary imaging techniques.

Before the early 1990s, we used two-dimensional radiation in which we literally planned the radiation on just one plane through the center of the prostate. It was very unsophisticated. Then with CT imaging and increased computing power, we were able to plan in a third dimension. There have been all sorts of more subtle improvements since then, such as intensity modulation. The best way to understand this is to think about searchlights intersecting and making a diamond in the sky. That’s what we have traditionally done using even beams of external radiation. Now we can modulate those beams to make, metaphorically speaking, an uneven searchlight. It’s stronger in some areas and weaker in others. When these beams intersect, they can actually create areas of radiation with shapes that are more complex than a diamond — shapes like a prostate, for example. Prostates are complicated because of their asymmetry and indentations. This technique allows much better beam shaping.

Is that what’s meant by conformal radiation therapy?

ZIETMAN: Well, “conformal” describes everything that has come since two-dimensional radiation, so all of the three-dimensional techniques are considered conformal because the volume is more accurately delineated. We have 3D-CRT, intensity-modulated radiation therapy, CyberKnife.… These are all sophisticated forms of 3D radiation. And we now incorporate CT and MRI information into our radiation planning. We plan the treatment in 3D.

What’s a patient likely to have done as part of his radiation planning?

ZIETMAN: I think almost all patients will have, at a minimum, a CT scan. Sometimes we’ll incorporate information from other modalities, such as MRI scanning.

LAMB: And we recommend an enema at the time of the simulation so that the rectum is at its smallest. Some centers use gold fiducials, small gold seeds to show where the prostate is. They serve as radiographic landmarks in mapping and to help in image guidance.

Has that replaced tattooing, where marks are made on the body to show the location of certain structures beneath the skin?

LAMB: It hasn’t replaced tattooing; it’s in addition to tattooing.

KAPLAN: Right. You see, the basic problem is that the prostate sits about 2 millimeters in front of the rectum. It sits right below the bladder, it has the urethra running through it, and it has the nerves that allow men to have erections plastered along each side. We’re trying to thread the proverbial needle, so we use all of these techniques to do the best job we can of treating the prostate while minimizing radiation to those areas.

Do you repeat CT or do a CT scan during radiation so that if there is a change in the shape of the gland or tumor, you can account for it?

LAMB: There are assumed to be changes every day. Even within a treatment there can be changes, mostly from rectal filling and emptying. That’s why you need some sort of marker to see how the prostate has shifted.

Some facilities can do a CT at the same time. Others will use some form of localization, most commonly the gold fiducials. Some people use ultrasound to help them see where the prostate is at a particular moment.

If a patient is going to have radiation therapy and the facility is not putting in gold fiducials, should the patient be concerned?

ZIETMAN: There are a number of issues here. First, the patient needs to know whether he’s being treated with an old-fashioned radiation dose or a high radiation dose. A high radiation dose is what we regard as the norm now because there’s plenty of evidence proving that it’s the best way to be treated.

Assuming the patient is being treated with a high dose of radiation, he will want to know that the prostate has been properly targeted and will be tracked every day throughout treatment. That could be done with gold fiducials, it could be done with ultrasound, it could be done with CT. There are many different ways of doing it, but there’s got to be some method of targeting and tracking.

What about someone who needs radiation and lives in a small, remote town? Should he travel to an academic medical center for treatment?

KAPLAN: Well, I think this technology has disseminated fairly rapidly throughout the country. It’s not unique to teaching institutions.

LAMB: In fact, I think some community-based practices implement new technologies even faster than large medical centers. It’s more a matter of asking the right questions than worrying about the name on the door.

Are there red flags a patient should be on the lookout for?

KAPLAN: I think the standard of care is some form of conformal therapy. There are special situations where we may not use it, but I think some sort of 3D is the minimum.

ZIETMAN: Yes, three-dimensional planning and daily tracking are essential. People can also ask about high-dose radiation, but there are situations in which we might not use it because of the risks. It’s a complicated issue.

Radiation dose

Let’s talk about the dose of radiation and how you measure it.

ZIETMAN: A long time ago, radiation was measured in roentgens. That was changed to rads. About 15 years ago, the unit of measurement became “Gray,” abbreviated “Gy.” A reasonable radiation dose for somebody with prostate cancer is between 70 and 79 Gy. There’s some evidence that the higher 70s are better than the lower 70s, so unless there’s a good reason, you probably shouldn’t be using the lower dose. Here at Massachusetts General Hospital, patients get 79 Gy.

What about at Mount Auburn Hospital?

LAMB: Usually 78 Gy, which is pretty much the same.

What would a patient get at Beth Israel Deaconess Medical Center?

KAPLAN: Most of our radiation therapy patients are also receiving adjunct hormone therapy. As a result, we use a slightly smaller radiation dose — between 72 Gy and 75 Gy. With hormones added, the impact is similar to a higher dose of radiation.

So in most patients the extraprostatic tissues, including the lymph nodes, do not have to be treated?

KAPLAN: Yes, that’s correct.

ZIETMAN: I wouldn’t treat the lymph nodes. I rarely treat lymph nodes.

LAMB: I only treat lymph nodes in high-risk patients. I think that’s where IMRT is an important tool to have because it can really decrease the toxicity of pelvic radiation.

How do you determine whether a patient is at low, intermediate, or high risk of having prostate cancer outside the gland?

LAMB: There are different calculators you can use. Memorial Sloan-Kettering Cancer Center has one available online. [Note: See “Prostate nomogram online,” below.] You plug in all the variables, such as Gleason scores. If the patient has more than a 15% risk of lymph node involvement, I consider treating their lymph nodes.

Prostate nomogram online

If you have been diagnosed with localized prostate cancer and want to better understand your risk and treatment options, you may be able to use Memorial Sloan-Kettering Cancer Center’s risk calculator, or nomogram. For more information, log on to www.mskcc.org/mskcc/html/10088.cfm.

ZIETMAN: There are published formulae and strict criteria for what constitutes low, intermediate, and high, but I also go with my gut. Obviously if the Gleason score is an eight, nine, or 10, the patient has high-risk disease. We tend to categorize patients, put them in boxes. But if I don’t want to give a patient a long course of androgen deprivation therapy, I may move him out of one category and into another based on other factors. For example, if a patient has a Gleason score of eight, but cancer was found in only one biopsy core and it can’t be felt during a digital rectal exam, and his PSA is only 4 ng/ml, I might treat him as if he has intermediate disease. I think the boxes have soft, flexible sides.

It sounds like there’s an art to medicine, that it’s more than a science.

KAPLAN: Correct. I think you always have to think about the data when you’re segregating patients into different treatment categories. You have to understand the biology of the disease. Certain factors might, from a numbers standpoint, put a patient into a higher or lower risk group. But from a clinical perspective, that might not make sense. It’s not pure science.

Thoughts on brachytherapy

What is brachytherapy? What advantages does it have?

KAPLAN: There are two types of brachytherapy. One is what we call low dose-rate, which is the permanent implantation of radioactive seeds into the prostate. The radiation decays over time. After several months, they are no longer radioactive. Then there’s something called high dose-rate, which is the temporary implantation of very high-dose radiation sources for very short periods of time over a few days.

I think the high-dose-rate method is more invasive. The needles and catheters that direct the radiation into the prostate have to stay in place for tens of hours because the radioactive material is applied to the prostate multiple times. (See “Radioactive materials for brachytherapy,” below.) It’s great for getting very accurate doses of radiation to the prostate. One of the big questions, though, is whether giving radiation in very high doses over a short period of time is more effective than other forms of radiation.

The implantation of radioactive seeds has been done since at least the 1970s, so it has a good track record. And we’ve gotten better at it because we now use ultrasound to guide seed placement. It’s a relatively simple procedure, but it is surgery, and it requires anesthesia.

How do you decide whether to use low dose-rate or high dose-rate?

ZIETMAN: Let me take a step back. Brachytherapy is a way of giving high doses of radiation to the prostate. You can give that radiation using high dose-rate or low dose-rate, but you’re giving a high dose in both cases. Low dose-rate just describes the slower rate at which the high dose is given; high dose-rate gives it in rapid flashes. I don’t use high dose-rate simply because I’ve got enough other options open to me. My chosen form of brachytherapy is low dose-rate.

What’s an appropriate dose?

ZIETMAN: This is a difficult concept to explain to patients. Because the low-dose-rate radiation is given much more slowly over an extended period of time, it’s less effective over all unless we give higher total doses. That’s why a person getting low-dose-rate brachytherapy will end up receiving 145 Gy or thereabouts, which sounds like an enormous dose. But biologically, it’s not much more than receiving 79 Gy with external beam radiation.

KAPLAN: It is hard to explain the dosing. Instead, we talk about how the biological effect is equivalent to external beam.

ZIETMAN: So, with high-dose-rate brachytherapy, you put the catheters in and you give one big pulse of radiation, a big fraction of radiation — maybe 6 Gy or thereabouts. Then you wait several hours and do it again. And then you repeat that the next day or the next week.

The biological principle underlying high-dose-rate brachytherapy is that you give it quickly and you give large doses for a few days. As Dr. Lamb was explaining earlier, it is possible that these large fractions of radiation have some biological advantages in prostate cancer. Possible advantages, though not yet proven.

Possible?

LAMB: We say “possible advantages” because high-dose-rate brachytherapy has been used only in conjunction with external beam radiation. There’s not much data on using high dose-rate alone, which is what the CyberKnife dose schedule is based on.

ZIETMAN: The problem with high-dose-rate brachytherapy is that you have to give it repeatedly, and to do that, you need to leave the catheters in the perineum, the area between the scrotum and the anus. It’s just not practical to give the entire course of radiation that way, so usually it’s given as a boost for some type of external beam radiation. I haven’t done any high-dose-rate brachytherapy because I think low-dose-rate brachytherapy is much easier for patients. It’s one treatment, it’s quick, you send the patient home the same day, and they’re done. Because it has to be combined with four or five weeks of external beam radiation, high-dose-rate brachytherapy lacks the most attractive features of low-dose-rate brachytherapy, namely speed and convenience.

What radioactive material do you use for brachytherapy?

ZIETMAN: Iodine-125 or palladium-103. They’re both used in low-dose-rate brachytherapy.

What about for high-dose-rate brachytherapy?

KAPLAN: Usually iridium-192. It’s hundreds and hundreds of times stronger than the dose administered by a little seed. That’s why they hook it onto a wire and pull it in and out of the prostate. The wire can move at different speeds, and that’s how it gives varying doses.

What do you use, Dr. Lamb? Dr. Kaplan?

LAMB: We use iodine for low dose-rate. We don’t use high dose-rate either.

KAPLAN: Same here.

Radioactive materials for brachytherapy

Isotopes are different forms of the same element; the number of neutrons in an atom of that element varies. Two isotopes are commonly used in permanent brachytherapy — iodine-125 and palladium-103. Iridium-192 is used for high-dose-rate brachytherapy. As they break down, the isotopes emit gamma ray energy that destroys cancer.

So, even though high-dose-rate brachytherapy is an option, none of you use it?

KAPLAN: That’s correct.

ZIETMAN: Those who do use it say they can put the radioactive material into the prostate and adjust the length of time it’s in the patient. They say that they can tightly shape the radiation to the prostate, and there’s some truth in that. They also say that there are possible biological advantages, but that’s unproven.

So a patient should not necessarily seek care elsewhere if their institution doesn’t offer high-dose-rate brachytherapy?

KAPLAN: That’s right.

ZIETMAN: Chances are, many institutions like Massachusetts General have high-dose-rate brachytherapy. It can be used for gynecologic cancers and skin cancers, where there are clear advantages to using it. We just don’t feel that the evidence is compelling enough to justify its use in treating prostate cancer.

KAPLAN: With any type of therapy, patients need to find a program that they’re comfortable with and that performs a lot of treatments. As physicians, we can’t offer everything to everyone, so we decided to have low-dose-rate brachytherapy be our focus in brachytherapy.

Who is an ideal patient for brachytherapy?

LAMB: I think the ideal patient for brachytherapy is someone with a very low risk of cancer outside the prostate, because brachytherapy focuses so tightly on the prostate itself. Patients with a higher risk of cancer outside the gland should not have brachytherapy. The size of the prostate also matters. A volume less than 60 ml is ideal. They should not have a lot of urinary symptoms and should not have had a transurethral resection of the prostate, or TURP. A brachytherapy patient also has a life expectancy of at least 10 to 15 years and needs to be able to tolerate anesthesia.

ZIETMAN: Yes, for brachytherapy, I like small cancers, small prostates, and a low level of urinary symptoms.

KAPLAN: I agree. They have to meet those criteria. I tell patients that brachytherapy is like a rifle shot on the prostate. It’s not designed to give radiation outside the prostate, so the chance that the cancer has spread has to be low. And the prostate cannot be big because we’ll have trouble getting the seeds in around the pelvic bone.

Thoughts on external beam radiation

Who is an ideal candidate for external beam?

LAMB: Almost anyone can have external beam. Usually, low-risk patients have other choices, such as surgery, brachytherapy, or active surveillance. Intermediate- and high-risk patients have fewer options, so external beam might be their best choice.

KAPLAN: For external beam, I think the ideal candidate is someone who can’t have brachytherapy or someone who has more advanced disease or a greater chance of having cancer outside the prostate.

Short of a definitive pathology report, what criteria do you use to determine whether the cancer has penetrated the prostate capsule?

KAPLAN: It’s a combination of major and minor factors. The major factors are absolute PSA, Gleason score, and rectal exam findings. The minor factors include the number of positive cores from the biopsy, the amount of cancer in the positive cores, and how rapidly the PSA is rising.

What about TomoTherapy?

LAMB: TomoTherapy has some potential advantages because you can do CT scanning as you go. It rotates 360 degrees around the patient. It’s like a CT scanner, but it also delivers radiation.

KAPLAN: It’s a variation of IMRT.

Dr. Zietman, you’ve been involved in the development of proton therapy and neutron therapy. Can you review their advantages and disadvantages?

ZIETMAN: Neutron beam is a form of external beam radiation, and there were a number of centers around the world that offered it. Not many in the United States — maybe two or three — and a couple in Britain. Back in the 1950s, it was thought that neutron therapy might have some biological advantages, but that never panned out. Indeed, there were excessive complications associated with neutron therapy, and all the neutron facilities were subsequently closed.

Proton beam therapy is a sharp, accurate form of radiation that has been used for several decades. There’s no biological advantage in using protons, but the radiation comes in a very controllable form. You can shape the beam nicely, you can stop it dead in tissue, and it has sharp edges. It’s got a long track record of treating eyes, face, skull, and spine tumors. It has proven equivalent to other forms of radiation therapy in treating prostate cancer, but I think it has yet to prove its superiority. Maybe it isn’t superior at all. We have yet to have a head-to-head comparison of protons versus IMRT or protons versus brachytherapy.

A lot of patients from around the world come to see you for proton beam therapy. How do you advise them?

ZIETMAN: Well, the first thing I do is open their eyes about what’s known and what isn’t. There are advantages to using protons in the other body sites I mentioned because they’re relatively close to the surface. Your eyeball, for example, is close to the body’s surface. The radiation is very sharp across short distances. But when you’re treating a prostate, the beam must reach the center of the body, so the edges aren’t sharp; they’re fuzzy. We’ve done planning studies comparing protons and IMRT, and certainly in the high-dose area, we haven’t seen any advantage to protons.

I say to patients, “You are going to be part of a clinical trial, you are going to be prospectively studied because patients have side effects and quality-of-life issues. We need to quantify these problems to compare them to other therapies.” Many patients come to me thinking that proton therapy is a slam-dunk, that there’s no risk of erectile dysfunction. This is absolutely wrong. They think there’s no risk of damage to their bladder or rectum. Absolutely wrong. Once I correct these misconceptions, some of them say, “Well, thank you very much, but I’m going back home to be treated with IMRT or brachytherapy.” I am happy to treat patients with proton beam therapy, but they need to be in a clinical study and have realistic expectations.

There are going to be advances in proton beam radiation over the next several years that will reduce the fuzzy edge — something called intensity-modulated protons — but that’s two or three years away.

Dr. Kaplan, you’ve been championing CyberKnife. Tell us about it.

KAPLAN: CyberKnife is a proprietary device. It’s a robotic arm that can move with very high precision. It has a special x-ray machine attached to its head so that it can move around the patient at many different angles. It delivers a very narrow beam of radiation, what we call a pencil beam. During treatment, the robot can move into, say, 200 different positions, aim, and shoot the radiation. All of those beams converge in a very small area. That’s how we can get a high dose into a small area with very little radiation falling outside that area.

So, it’s really a way of more finely focusing the radiation beam?

KAPLAN: Yes. But that’s only the first half of it. The other half of it is that you need some way to track what you’re doing. One of the keys to this device is that it takes x-ray images, and because we have the gold fiducial markers in the patient, we can verify that the prostate is in the appropriate position before it’s treated. If the prostate has moved, the robot adjusts. What we’re trying to do is take advantage of the theory that giving high doses of radiation in a very short period of time is effective. Patients have five treatments instead of a few dozen.

What is CyberKnife’s track record like?

KAPLAN: The machine has only been available for three or four years, so we’re gathering data as we go along. I think the early, unpublished data have been relatively good and that the results have been similar to other forms of radiation. There’s been nothing out of the ordinary. But it will take a while to prove long-term efficacy in the treatment of prostate cancer.

Dr. Zietman, what are your thoughts on CyberKnife?

ZIETMAN: I just think it has to be done as part of a clinical study because treating patients with these very large doses, or large fractions, comes with great risk.

LAMB: I agree that it should be used only in centers that are studying it carefully. We need to know how to use it to deliver radiation safely.

ZIETMAN: We have a very limited understanding of the biological response of tumors to radiation, particularly in prostate cancer. This has huge implications for what fraction size is safe.

KAPLAN: I should say that the doses and the fractionation schedule that we are using with CyberKnife emulates the five- to 10-year experience that people have had elsewhere using high-dose-rate brachytherapy with four to five treatments in a very short period of time. This method has a much longer track record.

It sounds like the bottom line for patients is that if they are considering protons or CyberKnife, they should enroll in a clinical study.

KAPLAN: Yes, absolutely.

Table 1: Comparison of forms of radiation therapy

Modality Ideal candidates Treatment time and recovery Possible side effects Advantages Disadvantages
3D-CRT (conformal radiation therapy) Older patients with multiple medical conditions; patients whose cancer has spread outside the prostate capsule; men who have had a transurethral resection of the prostate (TURP) or have a history of lower urinary tract symptoms. 35–44 treatments (five times a week for seven to nine weeks); each treatment takes about 15 minutes. Bowel problems (diarrhea, blood in stool, rectal leakage, rectal pain), frequent urination, blood in the urine, urinary incontinence (increases over time), impotence (develops slowly), fatigue. Widely available.Now the standard in outpatient radiation therapy. Length of treatment makes it inconvenient, especially for men living far away from a treatment facility or those who travel frequently.
IMRT (intensity-modulated radiation therapy) Same as 3D-CRT. 38–40 treatments (five times a week for seven to eight weeks); each treatment takes about 15–20 minutes. Same as 3D-CRT. In theory, allows more accurate targeting of the tumor so that there’s less damage to surrounding, healthy tissue. The intensity of each of the beams can be adjusted. Same as 3D-CRT.Not offered at every treatment facility.

In rare cases, may miss part of the tumor if the beam is too narrowly focused.

Proton beam therapy Same as 3D-CRT. Same as 3D-CRT. Same as 3D-CRT. May be able to deliver more radiation to prostate and less to surrounding tissues, causing less damage to nearby structures; protons release their energy after traveling a certain distance, limiting damage to the tissue they pass through. Only five sites in the United States.May not be covered by insurance.

More research is needed to determine whether it reduces side effects.

CyberKnife Same as 3D-CRT. One to five outpatient treatments; each treatment lasts a few hours. Same as 3D-CRT. Corrects for small movements and changes in the prostate during the course of treatment. Limited availability.More research is needed to prove its effectiveness.
TomoTherapy Same as 3D-CRT. Number of treatments varies depending on tumor characteristics. Each treatment lasts about 25 minutes. Same as 3D-CRT. Integrates daily CT scanning to correct for changes in the prostate. Beams rotate 360° around the patient for greater accuracy. Device on the market for only about four years; not available in all areas.
Permanent seed implants (brachytherapy) Men with early-stage cancer and prostate volume of less than 60 ml.May be beneficial in men with inflammatory bowel disease or cancer close to the bowel. Half-day to full-day outpatient procedure with anesthesia. Impotence and urinary and bowel problems.Pain and rectal problems, such as diarrhea and constipation, usually resolve in about a month. One-time treatment. Risk that seeds will migrate or be passed in the urine. Rarely, seeds enter bloodstream and travel to lungs or other parts of the body.
High-dose-rate brachytherapy Intermediate and high-risk patients. Usually three treatments over a few days; treatments last about 15 minutes. Same as permanent seed implants. Radiation concentrated in the prostate, potentially sparing the urethra, bladder, rectum, and nerves.Can be used with external beam radiation in high-risk patients. Needles remain in place until after the final treatment.Requires a hospital stay.

Originally published Jan. 1, 2008; last reviewed April 7, 2011.

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