High-Dose 3D Radiation Works On Prostate Tumors

High-dose radiation therapy appears to be every bit as effective as surgery in treating aggressive prostate tumors -- and is far more effective than standard low-dose radiation for some of the most virulent prostate cancers, according to researchers from the University of California San Francisco.

"Our study involved patients at high risk," said principal investigator Mack Roach III, MD, UCSF associate professor in radiation oncology and medicine. "But the results are similar to what's been reported for more favorable patients treated with surgery. The point is that many patients with high-grade tumors in particular might be better treated with radiotherapy.

"The second point is patients who had high-dose 3-dimensional radiation did much better than those treated with standard radiation therapy," he said.

Such high-dose therapy can only be administered using a recent technology called 3-dimensional conformal radiation, Roach says. This technology allows multiple x-ray beams of radiation to be designed with the use of computer software to pinpoint the exact shape of the prostate. Only the prostate receives the maximum dose of radiation, while minimal doses are delivered to adjacent tissues and organs.

In the UCSF study, 23 percent of 50 patients who received either high-dose or standard radiation therapy were disease-free after four years, nearly equal to the approximately 25 percent reported in two other studies conducted in 1994 at Johns Hopkins Medical Center and Baylor University School of Medicine of men with similarly aggressive tumors who underwent surgery.

In addition to how aggressive a tumor looks, prostate cancers also are measured in terms of how much of the tumor marker called prostate specific antigen (PSA) is produced. The higher the PSA score, the more serious the disease.

In a subset of about half of the study subjects, approximately 80 percent of the men who had moderate PSA scores but aggressive tumors were disease-free after three years if they were treated with high-dose radiation, compared to 15 percent of men with lower PSA scores treated with standard radiation therapy. Standard therapy offers comparatively low doses of radiation to avoid harming other tissues, according to Roach.

Results of the study were presented May 21st at the 32nd annual meeting of the American Society of Clinical Oncology in Philadelphia.

Although both radiotherapy and surgery may produce side effects such as impotence and incontinence, Roach said they tend to be less common with radiation.

"The quality of life is probably a bit better with radiotherapy," he said.

In addition, radiation may be used on some tumors that are inoperable. More than half of the patients in the study weren't considered surgical candidates.

One of the controversies in prostate treatment is whether many tumors should be treated at all, Roach said. Typically, most prostate tumors are slow-growing and many men will die of other causes before the tumor becomes dangerous.

Prostate cancer is the second leading cause of cancer death among men in the United States, after lung cancer, and the most common non-skin malignancy in men. The patients in the UCSF study had high grade tumors considered the most likely to be fatal.

The prognosis for patients who have prostate cancers usually is based on three assessments:

• The first measurement is the PSA blood test;
• A second measurement, made by digital rectal exam, assesses the location and volume of disease, or the "stage" of the tumor;
• A third measurement, which uses a microscope to evaluate how aggressive the tumor looks, is known as the "grade."

Study results indicated a dose response effect, with higher grade tumors requiring greater amounts of radiation.

Roach said patients with very low PSAs, as well as patients with very high PSAs, don't appear to benefit as much from high dose radiation therapy. (Men with low PSA scores are likely to do well whether they receive treatment or not, he said, while any treatment confined to the prostate will have little effect if the cancer has spread to other parts of the body, as is suggested by a very high PSA.)

The study found that radiation is effective on higher grade tumors, particularly in men who also have moderate PSA scores. The UCSF study of 50 high-risk men is part of a sample of more than 500 patients treated since 1987 at four hospitals. The hospitals included UCSF, UCSF/Mount Zion Medical Center, University of California-Davis Medical Center, and the Veterans Administration Medical Center in Martinez, Calif.

The research represents the first analysis of results from using higher than standard doses of radiation on high grade tumors at UCSF.

The study subjects were chosen because they were considered at highest risk for failing treatment and dying of prostate cancer.

Similar outcomes were found when the UCSF researchers expanded the study to nearly 100 patients that included men with slightly less aggressive (lower grade) tumors.

In addition to Roach, study researchers include Shane Meehan, MD; Stewart Kroll, MD; Michael Weill, MD; Lawrence W. Margolis, MD; and Theodore L. Phillips, MD, all of the UCSF Department of Radiation Oncology; Janice Ryu, MD, of the UCD Department of Radiation Oncology; Eric Small, MD, of the UCSF Department of Medicine; Joseph Presti, MD, Veterans Affairs Medical Center of San Francisco; and Peter C. Carroll, MD, UCSF Department of Urology.

The research was supported by a seed grant from the Radiology Society of North America, an American Cancer Society Career Development Award and the National Cancer Institute.

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