How Much Hormonal Therapy Is Sufficient?

A recent trial suggests that the standard duration of hormonal therapy is longer than necessary for many patients. In the study, men with localized, but high-risk prostate cancer who were treated with hormonal therapy for 18 months lived just as long as those treated for 36 months. The phase III trial was conducted at multiple hospitals in Quebec, Canada. Dr. Abdenour Nabid of Sherbrooke University Hospital Center in Sherbrooke, Quebec, is lead author of the study. He presented these results last month at the American Society of Clinical Oncology Genitourinary (ASCO GU) Symposium in Orlando, Florida.

The standard duration of hormonal treatment for localized, high-risk prostate cancer has been 2 to 3 years. According to Tomasz Beer, deputy director of the Oregon Health and Science University Knight Cancer Institute, the new data support a shorter 18-month therapy regimen going forward. Previous studies have also supported an18-month treatment duration.

“The results are practice-changing, but only to some extent,” Beer says. “We need to see complete data in a peer-reviewed publication to definitively decide whether these results are sufficient to define practice.”

The trial enrolled 630 men with node-negative, but high-risk prostate cancer who had been treated with radiation therapy. Patients were randomly assigned to receive either 18 months or 36 months of androgen blockade hormonal therapy. The treatment consisted of bicalutamide (Casodex) for 1 month, along with goserelin (Zoladex) every 3 months. (Androgen deprivation therapy is a form of chemical castration, or blockage of testosterone production, which is a known driver of prostate cancer.)

After a median follow up of 6.5 years, a small difference was seen in the median overall survival of men in the two treatment arms, but the difference was not statistically significant. Of the men who received 36 months of therapy, 77.1% were alive compared to 76.2% of the men treated for 18 months. A total of 147 patients died over the course of the trial—116 of these deaths were attributed to causes other than prostate cancer.

After 10 years, prostate cancer survival rates were similar for the remaining patients in both treatment groups. The death rate from prostate cancer was the same: 87.2% (P = .838). Rates of cancer spread—measured either by higher prostate specific antigen (PSA) levels or spread of the cancer to regional or distant sites—were also similar among the two treatment groups.

This trial was started back in 2000 to better define the duration of hormonal therapy needed for optimal patient outcomes. A European Organization for Research of the Treatment of Cancer (EORTC) study (Bolla, et al. N Engl J Med. 2009; 360:2516-27) previously determined that a 36-month androgen deprivation regimen combined with radiotherapy led to better overall survival compared to 6 months of hormonal therapy with radiotherapy.

The 36-month hormonal/radiotherapy regimen is a standard regimen for treating localized, high-risk prostate cancer patients. The goal of the treatment is to both control the tumor locally and prevent micrometastasis that could lead to full metastasis of the cancer.

Among men with localized prostate cancer, high-risk patients are a minority. High-risk patients are currently identified by several factors, including clinical stage, Gleason score, and PSA level.

“It is good news for patients with prostate cancer if we were able to achieve the same survival benefits with less therapy and consequently fewer side effects and costs,” Beer says.

An ongoing study is assessing whether quality of life differs between patients assigned to the 18-month and 36-month arms.