Treating
prostate cancer
Part V: Radiation therapy
Harvard
Men's Health Watch, September 1, 2008
Along with active surveillance and surgery, radiation therapy (also known as radiotherapy) is one of the major options for managing early prostate cancer, and it also has a well-established role in the treatment of more advanced disease. It has been hard enough for a man with early prostate cancer to choose among these alternatives, and the decision is getting even harder. That’s because radiation therapy is changing; there are now several options to choose from, including advanced methods for delivering external beam therapy, new techniques for providing internal radioactive seed therapy, and evolving strategies for combined radiation and hormonal treatment.
All forms of radiation contain energy; it’s what burns your skin after an ill-advised day at the beach. Radiation therapy delivers much more energy, enough to kill cells. Because cancer cells are growing faster than normal cells and are less able to repair radiation damage, radiation therapy can be used to treat many forms of cancer. The trick is to focus the radiation on the tumor as precisely as possible. In the case of prostate cancer, doctors can focus the energy of radiation from outside the body (external beam radiation therapy) or from the inside, by placing radioactive seeds within the prostate (brachytherapy).
External beam radiation therapy
External beam therapy has been used to treat prostate cancer since the 1950s, but it has improved greatly since the late 1980s.Today’s external beam therapy does not depend on one technique but on a choice between several methods. All aim to deliver more energy to the prostate and less to surrounding tissues. A 2005 trial demonstrates the value of this approach. It compared a conventional dose of radiation (70 Gray, or Gy; the unit is named for Dr. Louis Gray, a pioneer in radiotherapy) with a high dose (79 Gy). After five years of follow-up, the men who received high-dose therapy were the winners. Those with low-risk cancers were 51% less likely to have recurrent disease, while men at moderate risk enjoyed a 44% advantage over the participants who were treated with the conventional dose all without an increase in major side effects.
Radiation oncologists have three ways of administering high-dose external beam therapy:
Three-dimensional (3D) conformal radiation that delivers energy in the form of photons (electromagnetic waves) is the most widely available technique.
Intensity-modulated radiotherapy (IMRT) also delivers photons, but uses a different system to boost radiation to the prostate while diminishing the intensity of radiation that spills over to normal tissues. IMRT is more expensive than 3D conformal therapy and is less widely available.
Proton beam therapy is also available only at selected centers. It delivers energy in the form of protons (charged particles).
All three methods work well; like aerial warfare, they all depend on mapping and targeting for their success. After a man chooses external beam therapy, his first step is to undergo a CT scan. The CT image is relayed to a computer that constructs a precise three-dimensional map of his prostate and seminal vesicles. The map allows the radiation therapist to target precisely the cancerous tissues while shielding the healthy tissues nearby, including the vulnerable bladder and rectum. As a result, doctors can now deliver 15% more radiation with better cancer control and fewer complications (3% rectal bleeding vs. 15%).
Each radiation treatment is based on an initial computerized simulation. The therapist is responsible for placing the patient on the treatment table in precisely the right location and for being sure his bladder contains the same amount of urine each day. The next step is to position lead shielding blocks to protect normal tissues. Finally, the therapist activates the overhead linear accelerator that actually delivers the radiation. Each treatment is painless and quick, lasting just a few minutes. But because the therapeutic dose must be built up gradually, the treatments are repeated five times a week for seven or eight weeks.
Modern radiation therapy can be tricky, and the best results come from experienced centers. But if high-quality treatment is available, external beam radiation is a good choice for many men with early prostate cancer.
As with any form of treatment, the results are best for small, low-grade cancers that are confined to the prostate. Controlled trials have not compared radiotherapy to surgery or deferred treatment, but a prostate cancer registry study suggests that the three approaches have similar results for men with the most favorable prognosis, and those results are excellent, with 10-year cancer-survival rates above 90%. In an observational study of 2,311 men, radiotherapy patients didn’t fare quite as well (83% 10-year survival) as the surgical or watchful waiting patients (94% survival for both). For moderate-grade (Gleason score 5 to 7) and high-grade (Gleason score 8 to 10) cancers that are confined to the prostate, radiation does not seem as successful as surgery, but it appears similar to deferred treatment. Among men with such tumors, perhaps 45% to 75% expect 10-year survival following external beam radiation. The results of radiation therapy are less favorable for cancers that have spread beyond the prostate, but surgery is not an option for men with such advanced disease.
Until comparative trials are completed, it will not be possible for doctors to predict which form of treatment is best. But even now, it is clear that modern external beam radiation therapy procedures produce fewer side effects than surgery. Most men will experience fatigue and weight loss, but most can continue working throughout therapy. About 15% develop rectal symptoms (discomfort, diarrhea, bleeding) during or shortly after therapy, but long-term rectal problems persist in only about 3%. Similarly, bladder problems occur in about 10% early on, but persist in only about 3% of patients. Incontinence and bleeding are much less common than urinary urgency and frequency, which often respond to alpha blockers.
The reverse is true of erectile dysfunction, which becomes progressively more common as time goes by. In general, 40% to 50% of men experience erectile dysfunction within two years of radiation therapy; some respond to the ED pills Viagra (sildenafil), Levitra (vardenafil), Cialis (tadalafil), or other treatments. A 2004 study of 286 radiation-therapy patients reported that 64% were impotent and 4% incontinent five years after treatment; the corresponding rates for 901 radical prostatectomy patients were 79% and 15%, respectively. Bowel urgency and hemorrhoids were more prevalent in the radiation-therapy patients. Radiation therapy, whether delivered by external means or brachytherapy, appears to increase the risk of developing cancers of the bladder and rectum; the potential risk is small, but may be important for younger patients.
Since radiation therapy does not destroy the entire prostate gland, the PSA falls slowly and only rarely to undetectable levels. In addition, the PSA can “bounce” up and down following radiation. On average, it reaches its lowest level about a year and a half after successful therapy. Men with PSAs that fall to 0.5 nanograms per milliliter can expect the best results. Conversely, if the PSA rises from its low point on three consecutive tests taken three to six months apart, relapse is likely. As is the case with relapse following surgery, a rapid rise in PSA (called a short PSA doubling time) is the best predictor of clinical trouble.
Men who experience rapidly rising PSA levels after radical prostatectomy can receive salvage therapy a second attempt to control prostate cancer after recurrence of the disease in the form of salvage radiotherapy; salvage surgery is an option for some men who have relapses after radiation therapy, but the operation is technically difficult and carries a substantial risk of complications. Fortunately, both groups of patients can benefit from androgen-deprivation therapy.
All in all, external beam radiation therapy is a good option for men with prostate cancer. It is usually the treatment chosen by men older than 70 and by men with medical conditions that would make surgery hazardous or decrease life expectancy to 10 years or less. But even younger, healthier men with low-grade prostate cancer can benefit from radiation, and they should consider the merits and drawbacks of this option. Stay tuned for new approaches like the still-experimental CyberKnife technique that delivers external radiation but requires just a few treatments.
Other treatment methods
Surgery aims to cure prostate cancer by removing all malignant cells from the body. Radiation therapy strives for cure by destroying all cancer cells where they reside. And a variety of new ways to destroy the malignant prostate nonsurgically are being explored.The most advanced method is cryotherapy, which uses very cold temperatures to kill cancer cells by freezing them. Early results of cryotherapy were poor, but major technical advances in the 1990s have revived interest in the procedure. Rescinding a 1996 decision, Medicare began paying for the treatment in 2000, and the American Urological Association has accepted cryosurgery as “one of the methods of management of adenocarcinoma of the prostate,” but adds the important proviso that “the long-term curative efficacy of this treatment modality has not been established.” Although some doctors would apply that proviso to all treatment methods, cryotherapy really is very new and should still be regarded as experimental.
Other techniques to destroy the cancer cells are also being developed. High-frequency ultrasound is not approved for routine use in the U.S. but is being marketed by clinics outside the country. Men should understand that it is strictly experimental. Microwave thermal ablation and radiofrequency tumor ablation are among the approaches that are still in their infancy. Stay tuned for developments.
Brachytherapy
External radiation for prostate cancer dates back to 1915, when it was attempted by Dr. Hugh Young. Because of poor results, it was abandoned until the 1950s and 1960s, when better equipment made it possible. The year 1915 also marked the start of brachytherapy, when Dr. Benjamin Barringer of New York attempted to treat prostate cancer by placing radium needles within the gland. Because of many problems, internal radiation was abandoned until the 1970s when it was revived briefly, only to be discontinued again. But since the 1990s, interstitial (internal) radiation has been gaining momentum because improved imaging techniques are allowing doctors to implant tiny radioactive seeds directly in the prostate without surgery.Although it goes by many names, most doctors refer to implant therapy as brachytherapy. That’s because the radioactive seeds or pellets emit radiation that only travels a short distance; “brachy” comes from the Greek word for short. But since the radiation does not travel far, the seeds have to be placed in exactly the right location. Computed tomography and transrectal ultrasound (TRUS) now make that possible.
Brachytherapy is performed under general or spinal anesthesia. First, the doctor places an ultrasound probe in the patient’s rectum and often a Foley catheter in his bladder (see illustration). Next he uses TRUS and a computerized map of the prostate to guide his placement of the pellets, which are inserted through needles placed in the perineum (the area between the anus and scrotum). The procedure is over in an hour or two. Most patients can return home as soon as the anesthesia wears off, but men with bloody urine may have to use a urinary catheter for a day or two. Most doctors advise men to abstain from sex for about two weeks, and then use a condom for several weeks, but there are usually no other restrictions on the patient’s activity.
Brachytherapy
Brachytherapy is a relatively new way to kill prostate cancer cells with radiation. Using ultrasound as a guide, the doctor inserts fine needles into the prostate, then places radioactive seeds directly into the gland.
Most often the seeds are composed of radioactive palladium, gold, or iodine. Because these pellets stop emitting radiation after several months, they can be left in place permanently; in contrast, high-energy iridium seeds only remain in place temporarily. In either case, major rectal and bladder complications are uncommon. Because some seeds are placed near the nerves and blood vessels that surround the prostate, erectile dysfunction develops in about 20% to 70% of patients; ED treatment may help.
Compared to external beam radiation, brachytherapy has the disadvantage of requiring anesthesia but the advantages of requiring only a single treatment and of producing fewer complications. Because it’s newer, there is less long-term experience with brachytherapy, but it appears to be as effective as external beam radiation or surgery for low-grade cancers, but less effective than surgery for high-grade tumors. PSA levels often bounce around for a year or two after brachytherapy, making follow-up more complex than it is after surgery. Still, men who develop progressively and rapidly rising PSA levels after brachytherapy usually benefit from androgen-deprivation therapy.
Antioxidants and radiation therapy
Antioxidant supplements were the rage in the 1990s, but enthusiasm has dried up as study after study has found they provide no protection against either heart disease or cancer. In fact, one antioxidant, beta-carotene, actually boosts the risk of lung cancer in male smokers. In 2005, a Canadian study showed that antioxidant supplements may reduce radiation side effects in patients being treated for head and neck cancer. Unfortunately, however, this potential benefit was accompanied by an increased risk of the occurrence of second cancers and by diminished cancer-free survival. Doctors don’t know if these results apply to men receiving radiation therapy for prostate cancer, but, for now, the best advice is to avoid antioxidants during radiation. It’s a particularly important message for men considering vitamin E in the hope that it may protect the prostate.Combined radiation therapy
External beam radiation therapy and brachytherapy are both effective but is a combination of the two methods better than either one alone? It’s an interesting question, but like so many questions about prostate cancer, it has not yet been answered. In most cases, when these therapies are tried in combination, the seeds are implanted first. After about three months, when the seeds have lost some of their oomph, the patient receives a boost of low-dose external beam radiation. It’s a new approach, and experience is limited; still, early results suggest that combined radiation may provide extra seeds of hope for men with locally advanced, moderate-risk prostate cancer.Combined radiation and hormonal therapy
Many forms of therapy are available for prostate cancer. Since no method is clearly superior to the others, patients and physicians must together choose among the available options. And since no form of therapy is uniformly successful, doctors are increasingly recommending combined treatments, especially for men with more advanced or high-grade tumors.Combined radiation is one example. Another is the use of radiation following surgery. Surgery is the primary treatment. If a radical prostatectomy succeeds in removing all the cancer cells that can be identified, no additional treatment is necessary. But if the surgeon discovers cancer in the seminal vesicles, at the margin of the tissue that has been removed, or in the nearby lymph nodes, the surgery will not be curative. In that case, doctors often recommend a secondary treatment, usually external beam radiation or hormonal therapy.
When the secondary treatment is administered shortly after the primary treatment, it is called adjuvant therapy. But sometimes the ancillary therapy is administered before the main therapy in an attempt to shrink or reduce the stage of the tumor before definitive treatment. When it is administered first, the secondary treatment is called neoadjuvant therapy.
Although combination radiation-hormone therapy for prostate cancer is relatively new, it has proven useful for men with locally advanced disease (stages T2C and T3). The goal is to shrink the tumor and make it more responsive to radiation by depriving it of testosterone and other androgens (male hormones). Although various approaches are under study, they all use androgen-deprivation therapy before, during, or after radiation therapy. Men with low-risk disease do not need combination therapy, nor do men who receive high-dose radiation therapy. But results are encouraging for men with rapidly rising PSAs and locally advanced disease, reporting improved control of the tumor, fewer recurrences, and improved survival. Combination therapy does produce more side effects than radiation alone, and men with heart disease or other important medical problems may not benefit. More study is needed.
Unfortunately, neoadjuvant androgen-deprivation therapy does not appear to improve the results of radical prostatectomy but early androgen-deprivation therapy after surgery may help men who have microscopic deposits of cancer cells in their lymph nodes.
Androgen-deprivation therapy can be very beneficial on its own, often providing good control of advanced prostate cancers. It’s the subject of next month’s final report on prostate cancer therapy.
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