18 MONTHS OF ADT MAY BE ENOUGH FOR HIGH RISK PROSTATE CANCER 

Long-term androgen blockade in men with high-risk localized prostate cancer can be safely reduced from the current standard of 36 months to 18 months without compromising survival, according to results from a phase 3 trial.

At a median follow-up of 77 months, overall survival rates were comparable in the 36-month and 18-month treatment groups (77.1% vs 76.2%), according to lead study author Abdenour Nabid, MD, associate professor at Centre Hospitalier Universitaire de Sherbrooke in Quebec, Canada.

He spoke at an American Society of Clinical Oncology presscast being held in advance of the 2013 Genitourinary Cancers Symposium, February 14 to 16, in Orlando, Florida.

All of the men in the study were also treated with radiotherapy.

"This may very well change the standard of care in patients with this stage of disease," said presscast moderated Bruce J. Roth, MD, who is professor of medicine in the division of oncology at the Washington University School of Medicine in St. Louis, Missouri.

The study involved high-risk men, defined as having at least 1 of the following risk factors: T3 to T4 disease, a prostate-specific antigen (PSA) level above 20 ng/mL, or a Gleason score above 7. All of the men had node-negative disease.

About 15% of all localized prostate cancers are high-risk, said Dr. Roth.

The combination of radiotherapy plus long-term androgen deprivation is one of the standard treatments for these men.

The typical duration (range, 24 - 36 months) was established in 2 previous clinical trials, according to the study authors. The 36-month duration was chosen "almost randomly," Dr. Roth pointed out. "The optimal duration of androgen blockade is not yet defined," noted Dr. Nabid.

The impetus to shorten the duration of androgen deprivation is to diminish the related adverse effects, which collectively can make patients "quite miserable," said Dr. Nabid.

The longer the therapy, the lower the likelihood that testosterone levels will recover, said Dr. Roth. "There is a price to pay if you permanently reduce testosterone to castrate levels," he noted, referring to the many adverse effects of androgen deprivation, which include an increased risk for cardiovascular disease, hot flashes, loss of libido, erectile dysfunction, weight gain, loss of bone density, loss of muscle mass, and depression.

The study results presented thus far have not included any data on adverse events.

With less androgen deprivation therapy, the cost of treatment for high-risk prostate cancer also goes down, said Dr. Nabid.

"For the benefit of the patients, we hope these results will convince doctors that they can stop hormone therapy after 1 and a half years instead of 2 to 3 years," he said in a press statement.

Survival Data and More

The 630 study participants (average age, 71 years) were randomized to either 36 or 18 months of androgen-blockade therapy, consisting of bicalutamide 50 mg (a nonsteriodal antiandrogen) for 1 month and goserelin 10.8 mg (a luteinizing hormone-releasing hormone [LHRH]) every 3 months before, during, and after pelvic and prostate radiotherapy.

From October 2000 to January 2008, 310 patients were randomized to the 36-month group and 320 to the 18-month group. Most had T2 to T3 disease.

At 5 years, overall survival in the 36-month and 18-month treatment groups was comparable (92.1% vs 86.8%; P = .052); the same was true at 10 years (63.6% vs 63.2%; P = .429).

Similarly, at 5 years, disease-specific survival in the 36-month and 18-month treatment groups was comparable (97.6% vs 96.4%; P = .473); the same was true at 10 years (87.2% vs 87.2%; P = .838).

In addition, there were no significant differences between the 2 treatment groups for a host of other measures: biochemical failure, second course of androgen blockade therapy, pelvic node metastases, bone metastases, and causes of death.

At 77 months, 71 of 310 patients (22.9%) in the 36-month group and 76 of 320 (23.8%) in the 18-month group had died (P = .802).

The main causes of death for all patients were a second cancer (7.3%), prostate cancer (4.9%), and cardiovascular disease (4.4%). Age was the only risk factor that was statistically significant in the study. "Older patients die more rapidly," said Dr. Nabid.

The combination of bicalutamide and goserelin, which is a LHRH agonist, is a strategy known as androgen blockade, and is a somewhat controversial choice, Dr. Roth told Medscape Medical News in an interview. It is "almost universal" clinical practice to either use an LHRH agonist or remove the testicles to achieve castrate levels of testosterone. But the utility of adding an antiandrogen (in this case bicalutamide) is a matter of debate, he said.

This study was sponsored by AstraZeneca Pharmaceuticals. The authors have disclosed no relevant financial relationships.

2013 Genitourinary Cancers Symposium (GUCS): Abstract 3. To be presented February 14, 2013.