BOSTON—Combining long-term hormone therapy with radiation therapy for locally advanced prostate cancer significantly improves local progression, disease-free survival, freedom from distant metastasis, and biochemical control, according to results of a phase III clinical trial presented at the American Society for Therapeutic Radiology and Oncology (ASTRO) annual meeting.
In this prospective study of 1,520 patients with T2c-T4 prostate cancer, 5-year disease-free survival was 54% for those who received long-term androgen deprivation, compared with 34% for those who were given short-term hormone therapy (P = .0001).
While both groups had close to 80% 5-year overall survival (78% for long-term vs 79% for short-term), only 4.2% of the long-term hormone therapy group died of prostate cancer, compared with 7.2% of those who received short-term hormones.
Gerald Hanks, MD, of Fox Chase Cancer Center, chair of the multicenter trial, told ONI, “For this group of patients, long-term hormones and radiation is the standard of practice. It is the only treatment that has been proven by prospective trials. It’s the best you can get.”
Forty institutions and 100 of their affiliates contributed cases to the trial—the largest phase III study to date of radiation therapy for prostate cancer. Participation was so strong that the Radiation Therapy Oncology Group (RTOG) opened the trial in June 1992 and closed it only 3 years later.
Commenting on the report of the study at the ASTRO meeting, William Shipley, MD, of Massachusetts General Hospital, Boston, said, “The glory of this trial is, it was all done in the PSA era.”
All patients in the study received goserelin(Drug information on goserelin) (Zoladex) and flutamide(Drug information on flutamide) (Eulexin) for 2 months before and 2 months during external beam radiation therapy (65 to 70 Gy). Afterward, they were randomized to one of two groups—one group received no further therapy, the other had an additional 24 months of goserelin alone. The median follow-up was 4.8 years.
In addition to improving disease-free survival, the long-term androgen therapy group showed better results than short-term hormone treatment in terms of clinical local progression (6.2% vs 13%, respectively, P = .0001), distant metastasis (11% vs 17%, P = .001), and ASTRO-defined biochemical failure (21% vs 46%, P = .0001).
The long-term group did have an increase in RTOG grade 3 and 4 bowel complications: 42 patients, compared with 26 patients on short-term therapy.
In a subset of high-risk patients with Gleason score 8-10 tumors, only 12 who received long-term hormone therapy died of prostate cancer, compared with 29 in the short-term group. Their overall survival was also better at 5 years (80% vs 70%).
Referring to two previous studies that also supported long-term hormones for advanced prostate cancer, Dr. Hanks said he foresees no role for short-term hormone treatments in locally advanced prostate cancer. “I think the decision is between none and long-term,” he said. “These three studies have pretty much proven the role of long-term hormones in high-risk cases,” he said.
Although several retrospective studies presented at ASTRO considered hormone therapy for less-advanced patients (see article on page 32), Dr. Hanks reserved judgment on hormone use for low- and intermediate-risk patients until clinical trials now underway are completed.
Making Treatment Decisions
Despite the preponderance of evidence supporting long-term androgen deprivation in advanced disease, some physicians still do not prescribe it. “There are lots of them,” Dr. Hanks conceded. “I don’t know whether it’s because they don’t believe the studies or they make the decision for the patient.”
Androgen depletion is associated with significant side effects. “It means impotence, hot flashes, loss of energy, and osteoporosis. That’s not a trivial package at all. It’s a big package,” Dr. Hanks said.
He argued that the physician should provide full information, but the patient should make the final decision. “The patient has to weigh interference with quality of life against a 50% decreased chance of having prostate cancer at 5 years,” he said.
As chairman of the Department of Radiation Oncology at Fox Chase, Dr. Hanks created a Prostate Cancer Risk Assessment Program that provides this kind of counseling as well as screening.
Some Patients Decline
Each year, one or two patients decline long-term androgen depletion, usually because they want to preserve potency, Dr. Hanks said. Some are younger men early in their marriages, he added. “We’ll treat them as well as we can. With good treatment, we can push [their chances of 5-year disease-free survival] up to 45%, but they’re taking short odds,” he said.
Dr. Shipley noted that in the future, “we may be able to identify which men will benefit from long-term androgen deprivation, and then we’ll be able to spare others from the difficult side effects of these drugs.”
