Hormones May Benefit Select Early Prostate Cancer Patients

BOSTON—Short-term hormone therapy may benefit patients with localized intermediate- and high-risk prostate cancer, according to three retrospective studies presented at the American Society for Therapeutic Radiology and Oncology (ASTRO) annual meeting.

While the authors said that their results support the use of short-term androgen ablation in these patients, they emphasized that their results do not carry the same weight as the recommendation, based on randomized trials, that long-term hormone suppression be the treatment standard for patients with locally advanced prostate cancer.

The consensus was that validation for hormone therapy in patients with localized disease might come from two prospective randomized clinical trials being conducted by the Radiation Therapy Oncology Group and Dana-Farber Cancer Institute. Both studies are nearing completion.

Anthony V. D’Amico, MD, PhD, chief of genitourinary radiation oncology, Dana-Farber Cancer Institute, expressed the hope that his study would bolster the practice of physicians who now give hormone therapy even though androgen deprivation has not yet been proven conclusively to work in patients with localized disease.

“That’s why the study was done—to provide some support, but not conclusive evidence, that it may help,” he said. “Without randomized trials, no conclusions can be made.”

Dr. D’Amico, associate professor of radiation oncology, Harvard Medical School, reported on a retrospective cohort study of 1,586 men with clinically localized prostate cancer treated between January 1989 and August 1999.

All received external beam radiation therapy, but only 276 also received androgen suppression therapy for 6 months—2 months before, 2 months during, and 2 months after radiation therapy. The main outcome studied was prostate-specific antigen (PSA)-failure-free survival after 5 years.

For low-risk patients, hormone therapy did not make a difference statistically. Five-year PSA-failure-free survival was 92% among those who had radiation therapy plus androgen suppression therapy and 84% among those who had radiation therapy only (P = .09).

Among intermediate-risk patients, however, 86% of those given radiation therapy plus hormone therapy were free from PSA failure after 5 years, compared with 62% of the radiation-therapy-only patients (P = .0008).

High-risk patients also did better with hormone therapy than without it. Slightly more than two thirds (67%) of the group receiving radiation therapy plus hormone therapy achieved 5-year PSA-failure-free survival vs less than half (43%) of those who had radiation therapy without hormone therapy (P = .009).

One limitation of the study, Dr. D’Amico said, was that the median follow-up for patients receiving radiation therapy plus hormone therapy was shorter (by 2 to 6 months depending on the risk group) than for those who received radiation therapy alone.

Another concern, he said, was the definition of intermediate risk by PSA level, biopsy Gleason score, or the 1992 American Joint Commission on Cancer (AJCC) clinical T stage used by other groups studying hormone therapy.

“I get worried when people define intermediate risk as any one of these factors or high risk as any two,” he said. “With these definitions, an intermediate-risk patient can have a PSA of 25 ng/mL and a Gleason of 6, and a high-risk patient can have a PSA of 12 ng/mL and a Gleason of 3+4 equal to 7. That doesn’t make sense to me.”

Dr. D’Amico said: “It is possible that the addition of hormones in intermediate- and high-risk patients, as defined, may lead to a long-term benefit in outcomes, but it is not conclusive.”

Low-Risk Patients Don’t Benefit

Patrick Kupelian, MD, of the Cleveland Clinic Foundation, also looked at biochemical relapse-free survival in a study of 974 men with localized prostate cancer treated with external beam radiation therapy between 1986 and 1999. One fourth (247) of the patients received hormones for 6 months or less. Median follow-up was 43 months.

The researchers found that low-risk patients were least likely to have received hormone therapy and that the few who did showed no significant benefit, compared with those who did not. The 5-year biochemical-relapse-free survival rate for low-risk patients was 94% for those receiving radiation therapy plus androgen suppression and 81% for those who received radiation therapy only.

Based on these results, but emphasizing that longer follow-up is necessary, the authors recommended against giving hormone therapy to low-risk patients. “So far, as far as we can tell,” Dr. Kupelian said, “giving hormones to low-risk patients only adds toxicity to the treatment. Considering the cost of the treatment and its potential side effects, such as hot/cold flashes and loss of libido, hormonal therapy shouldn’t be offered as an option for low-risk patients.”

For intermediate- and high-risk patients, however, the addition of hormone therapy made a significant difference and was recommended by the researchers. In the intermediate-risk group, 98% of those who received hormone therapy, but only 56% of the radiation-therapy-only group, met the 5-year goal. Among high-risk patients, the rates were 85% and 30%, respectively.

Radiation dose also was an important factor, Dr. Kupelian said. Patients receiving hormone therapy also received higher radiation doses—88% had doses higher than 72 Gy. “Comparing the dose groups with or without hormones, there were trends,” he said, “but they did not reach statistical significance in this study.”

Hormones Plus Brachytherapy

Hormone therapy also showed good results in a study of patients treated with permanent radioactive seed implantation (brachytherapy) alone or in conjunction with androgen suppression.

Lucille N. Lee, MD, and her colleagues in the Radiation Oncology Department, Mount Sinai School of Medicine, New York, reviewed the records of 201 patients treated from October 1990 to September 1998 for moderate- to high-risk prostate cancer.

Moderate risk was defined as having one of the following risk factors: PSA greater than 10 ng/mL but less than 20 ng/mL, Gleason score of 7, or stage T2b. High risk was defined as having two or more of these risk factors, or PSA greater than 20 ng/mL, Gleason of 8 to 10, or stage T2c-T3.

Two thirds of the patients underwent androgen suppression for 3 months prior to brachytherapy and for 2 to 3 months afterward. Median follow-up was 42 months.

“Hormone therapy was the most significant factor associated with an improved outcome,” Dr. Lee said: 79% of the 134 patients who underwent hormone therapy were free from biochemical failure after 5 years vs 54% of the 67 patients who had brachytherapy only (P = .00001).

The researchers looked at patients who underwent hormone therapy and received a high radiation dose, Dr. Lee said, in the belief that this was the optimal treatment for this patient population.

“For intermediate-risk patients receiving hormone therapy and high-dose brachytherapy, there was 94% freedom from biochemical failure after 4 years. This is a very favorable outcome that is comparable to that of low-risk patients,” she said. “For high-risk patients, there was a 77% freedom from biochemical failure at 4 years, which suggests there’s some room for improvement.”

Based on this study and prior studies, Dr. Lee concluded, hormone therapy with a high-dose radiation therapy implant is a reasonable treatment option for intermediate-risk patients. For high-risk patients, the group’s current protocol is more aggressive, using hormone therapy in combination with an implant and external beam radiation.