Higher doses of targeted radiation better than expected for aggressive early prostate cancer
ANN ARBOR, Mich. - Early-stage prostate cancer patients with the most aggressive form of the disease may
benefit more from high doses of carefully delivered radiation than previous reports would suggest, a new
multicenter study led by current and former University of Michigan Comprehensive Cancer Center
researchers has found.
X-rays delivered to the exact three-dimensional location of 180 high-risk
tumors kept 79 percent of early-stage patients cancer free for at least five years - a definite
improvement over the usual 50-percent recurrence rate for those with this level of risk who have their prostates removed or
have lower-dose radiation therapy.
Higher doses show a clear positive effect, the study found by comparing results of this new study with years of U-M research into
lower radiation doses for less-severe prostate cancer and other tumors.
The research involved only patients with rarer but more often deadly forms of prostate cancer. But its
results suggest that higher doses of 3-D conformal radiation, as it is called, may help prostate cancer patients
with less-dangerous types of the disease, says study senior author Howard Sandler, M.D., associate
professor and associate chair of radiation oncology in the U-M Health System.
"This new evidence of an advantage from higher doses not only validates the use of this approach in this
subgroup of high-risk patients, it also hints strongly that lower-grade tumors could be vulnerable to
increased radiation delivered with careful planning," says Sandler.
Sandler and former U-M fellow John Fiveash, M.D., now at the University of Alabama-Birmingham, teamed
with researchers from the U-M the Fox Chase Cancer Center in Pennsylvania and the University of
California, San Francisco to pool data for the study.
They looked back at how well patients with the highest-grade kinds of tumors did after treatment with
radiation doses as much as ten percent more intense than conventional levels. As with all 3-D conformal
radiation therapy, patients received the doses after high-resolution images of their individual tumors allowed
doctors to plot the best angles for aiming the radiation beam at the tumor's exact outline, while skirting
important normal tissue like the bladder and hip bones.
3-D conformal radiation therapy was pioneered clinically in the mid-1980s. It combines recent advances in medical imaging, which allow 3-D images to be made of the body with
high resolution, with sophisticated radiation equipment that can produce many thin beams of intense X-rays
and aim them with pinpoint accuracy. It has few side effects.
Physicians can look at a virtual representation of a tumor with a "beam's eye view" that shows them the
irregular cross-section shape of each patient's cancer and predicts exactly where each beam of radiation will
pass through the body. Then, using planning software, careful patient positioning and specially designed
shutters for the X-rays to pass through, they can generate a combination of beams from different angles that
will intersect when they reach the tumor. "This delivers a combined dose of radiation powerful enough to kill
cancer cells, even though the individual beams leave nearby normal tissue relatively unscathed," says
The new study looked at the survival time and cancer-free time -- defined as the period in which patients'
blood showed no increase in prostate-specific antigen, or PSA -- of patients whose cancer cells showed
microscopic evidence of being especially aggressive.
Pathologists rate tumor biopsy samples from 1 to 10 on what is known as the Gleason scale, which ranks
"normal" looking cells low and gives higher scores to more abnormal-looking ones which have the potential to
grow out of control. All patients in the study had the highest Gleason ratings, from 8 to 10 - ratings that
appear relatively rarely among all prostate cancer patients but disproportionately among the 39,000 men
who die from the disease each year.
In addition to Gleason score, which rates the tumor's growth potential, the study also looked at the stage of
each patient's cancer at the time of radiation therapy. Stages, ranging from 1 to 4, rate how far the cancer
has spread within, around and beyond the prostate.
Patients in the study received radiation almost daily for several weeks, resulting in doses that ranged from
the currently conventional - around 66-70 Gray, or Gy - all the way up to 80 Gy. Even though the difference
in dose sounds small, the increase in radiation effect upon the tumor is large.
Of the 180 patients, 61 percent had a Gleason score of 8, and 57 percent had stage 1 or 2 cancer. Their
average age was 72, and follow-up time averaged three years but ranged up to 8 years. Some patients took
hormone-reducing drugs as well, though no effect was seen.
In all, 62.5 percent stayed within PSA limits, showing no recurrence of their cancer, for five years, and 67.3
percent survived five years. But, Sandler says, "the most dramatic effect was seen in stage 1 or 2 patients
with lower pre-treatment PSA levels who received the highest radiation doses - suggesting that the therapy
works best for those who catch their aggressive cancer early. By comparison, recent examinations of
conventional radiation therapy and surgery have shown recurrence rates higher than originally thought."
This study is based on multicentered research. Results are published in the current issue of the International Journal of Radiation Oncology, Biology and Physics (abstract not yet online). See also:
[Int J Radiat Oncol Biol Phys 2000 Jan
15;46(2):391-402 Preliminary report of toxicity following 3D radiation therapy
for prostate cancer on 3DOG/RTOG 9406.
Michalski JM, Purdy JA, Winter K, Roach M 3rd, Vijayakumar S,
Sandler HM, Markoe AM, Ritter MA, Russell KJ, Sailer S, Harms WB,
Perez CA, Wilder RB, Hanks GE, Cox JD
Mallinckrodt Institute of Radiology, St. Louis, MO 63110, USA.]