High-dose versus conventional-dose external beam radiation therapy

Two randomized trials have compared highdose to conventional-dose external beam radiation therapy. The MD Anderson trial evaluated approximately 300 patients. For the patients with a PSA > 10 ng/mL, there was a clear advantage in terms of freedom from biochemical or disease failure at five years with high-dose radiation (78 Gray) compared to conventional-dose radiation (70 Gray). They didn’t see an advantage for high-dose radiation in patients with a PSA ≤ 10 ng/mL (Pollack 2000, 2002).

The second randomized trial — the Massachusetts General Hospital/Loma Linda University trial — compared high-dose (79 Gray) to conventional-dose (70 Gray) radiation in men who mainly had low-risk disease. Of the 393 patients randomly assigned, approximately 250 had low-risk disease. The number of biochemical failure events at five years was halved for the patients with lowrisk and intermediate-risk disease who were treated with high-dose radiation therapy (Rossi 2005; Zietman 2004).

Radiation therapy patterns of care

Every five years, the Patterns of Care Study (PCS) group surveys about 60 academic or community-based institutions across the United States. It reviews five to 10 randomly chosen patients from each institution to obtain a snapshot of what’s going on nationally. In 2004, it reported the 1999 data and compared them to the 1994 data. Hormonal therapy is being used more frequently with radiation therapy in patients with localized prostate cancer, indicating the penetration of randomized trial data into clinical practice (Zelefsky 2004; [2.1]). When we break out hormonal therapy use by low-, intermediate- and high-risk prostate cancer, we find many men with low-risk disease who are receiving hormonal therapy with radiation therapy (Zelefsky 2004), a situation for which we have no randomized trial data showing any clear advantage.

High doses of radiation are now more frequently used (Zelefsky 2004; [2.1]). This trend is actually ahead of the randomized trial data. Both the PCS (Zelefsky 2004) and the CaPSURE database (Cooperberg 2004) are showing that external beam radiation therapy is being used less frequently and brachytherapy is being used more frequently in early-stage disease. In 1994, of the cases treated with radiation therapy in the United States, only three percent utilized brachytherapy. By 1999, it was up to 36 percent (Zelefsky 2004; [2.1]), and I can assure you by now it’s well above that. The CaPSURE database demonstrates that external beam radiation therapy is being used only a third as frequently in the sites they surveyed (Cooperberg 2004).

Impact of brachytherapy on PSA

We’ve learned that after brachytherapy, we have to sit on our hands for three or four years. If the PSA goes up, we need to ignore it. In fact, we could make a case for not checking the PSA at all in the first three years, which is hard to sell to patients. The median time to the PSA bounce is about 18 months, and it should be heading down again within the third or the fourth year. If it’s not, there is probably something wrong. The PSA after brachytherapy keeps going down, and at seven or eight years, the median PSA is lower than at four or five years.

Androgen deprivation therapy plus radiation therapy

RTOG-8610 (Pilepich 2001) and RTOG-9202 (Hanks 2004) are maturing. Every time they’re republished, the benefit from adjuvant androgen deprivation therapy seems to be confirmed. We now think about the use of adjuvant androgen deprivation with radiation therapy as follows: Patients with low-risk disease don’t need it, and patients with high-risk disease do. We can probably use less hormonal therapy if the patient has a Gleason 7 tumor and a PSA below 20 ng/mL. The patient needs more, maybe two or three years of hormonal therapy, if he has both high Gleason grade and PSA. The patients with intermediate- risk disease are an intriguing group. Anthony D’Amico published the results from a randomized trial in JAMA 2004, in which a little over 200 men with intermediate-risk prostate cancer were randomly assigned to receive radiation therapy alone or with six months of hormonal therapy. Combined androgen blockade was administered two months before, two months during and two months after conventional-dose radiation therapy. Not only did the trial show a disease-free survival advantage, but it has also shown an overall survival advantage at only five years (D’Amico 2004; [2.2]).

Select publications

Dr Zietman is a Professor of Radiation Oncology at Massachusetts General Hospital at Harvard Medical School in Boston, Massachusetts.