Part V: Radiation therapy
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
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
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
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
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.
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 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
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
© 2000-2007, President and Fellows of Harvard College.