Men with localized high-risk prostate cancer treated with adjuvant radiotherapy had similar overall and disease-free survival when treated with 18 months of androgen deprivation therapy vs 36 months of androgen deprivation therapy, the current standard of care in this setting. These results were reported at the 2013 ASCO Genitourinary Symposium1 and again at the 2013 ASCO Annual Meeting.2
Potential New Standard?
“[Androgen deprivation therapy] of 18 months could represent a threshold effect with no further gain in survival compared with 36 months of [androgen deprivation therapy]. Duration of side effects and treatment cost could be significantly reduced with a shorter course of [androgen deprivation therapy] compared with 36 months. With longer follow-up, 18 months of [androgen deprivation therapy] may become the standard in this setting,” stated lead investigator Abdenour Nabid, MD, Associate Professor at Sherbrooke University Hospital Center, Sherbrooke, Quebec, Canada.
The side effects of long-term androgen deprivation therapy are difficult for men to tolerate, and include depression, loss of sexual function and libido, reduced bone mineral density, reduced insulin sensitivity, increased serum triglycerides and cholesterol, and loss of muscle mass.
The optimal duration of androgen deprivation therapy in this setting is unknown, Dr. Nabid told listeners. An earlier European Organisation for Research and Treatment of Cancer study found that the standard 36 months of androgen deprivation therapy improved overall survival compared with 6 months in men with high-risk prostate cancer.3 The present study evaluated an intermediate duration of androgen deprivation therapy—18 months—vs 36 months, which cuts the time on treatment in half. The hope was to achieve similar efficacy with fewer side effects.
Study Design
The study was conducted at 10 centers in Quebec, Canada from October 2000 through January 2008 and included 630 men with high-risk prostate cancer, defined as having at least one of the following three risk factors: T3–4 stage, prostate-specific antigen (PSA) > 20 ng/mL, and Gleason score > 7. Participants were aged 18 to 80 (median, 71 years), had no evidence of residual disease or distant metastases, and no history of previous malignancy.
The primary endpoints were overall survival, disease-specific survival, and quality of life. Secondary endpoints were disease-free survival by chemical failure and site of relapse.
Patients were treated with 1 month of bicalutamide and then randomly assigned in a 1:1 ratio to androgen deprivation therapy with goserelin (Zoladex) for 36 vs 18 months. Radiation therapy to the pelvis and prostate was started 4 months after initiation of androgen deprivation therapy and was similar in both arms of the study.
“This was a very high-risk population of patients with prostate cancer,” Dr. Nabid emphasized. About 25% had stage T3–4 disease, 44.3%% had PSA > 20 ng/mL, 60% had Gleason scores > 7, 40% had a Gleason score of 8, and 20% had Gleason scores of 9 or 10. Treatment arms were comparable for high-risk features.
Major Results
At a median follow-up of 78 months (6.5 years), the survival rate was 77.1% in the 36-month group vs 76.2% in the 18-month group, a difference that was not statistically significant.
The biochemical failure rate was higher in the 18-month androgen deprivation therapy group (24.7% vs 19.7%), but this difference was not statistically significant. Among 140 patients who received a second course of androgen blockade, biochemical failure rates were 19.4% for the 18-month group vs 15.5% for the 36-month group.
No differences in frequency and site of metastasis were observed between the two treatment arms. The rate of pelvic node metastasis was 1.3% in both arms, and the rate of bone metastasis was 8% in both arms.
“This was very efficient treatment in either arm. This shows that longer duration of [androgen deprivation therapy] does not prevent bone metastases,” Dr. Nabid said.
Further Analysis
No significant differences were found for causes of death between the two arms. Overall, there were 165 deaths (26.2%). The most common cause was a second cancer: 6.1% in the 36-month arm vs 8.8% in the 18-month arm. The rate of prostate cancer–related death was similar between the two arms: 5.2% and 5.9%, respectively. There were 25 deaths due to other causes, and these were evenly distributed between the two treatment arms.
A multivariate analysis found that age and Gleason score > 7 were the only factors significantly associated with overall survival.
Among participants who were followed for 10 years thus far, overall survival and prostate cancer-specific survival are similar for both groups, he said, and Dr. Nabid expects that this will remain true with additional planned follow-up of 2 to 3 years.
The quality-of-life data are extensive but are not yet analyzed. They will be reported later this year. ■
Disclosure: Dr. Nabid has received research funding from AstraZeneca.
References
1. Nabid A, Carrier N, Martin A-G, et al: High-risk prostate cancer treated with pelvic radiotherapy and 36 versus 18 months of androgen blockade: Results of a phase III randomized study. 2013 Genitourinary Cancers Symposium. Abstract 3. Presented February 14, 2013.
2. Nabid A, Carrier N, Martin A-G, et al: Duration of androgen deprivation therapy in high-risk prostate cancer: A randomized trial. 2013 ASCO Annual Meeting. Abstract LBA4510. Presented June 4, 2013.
3. Bolla M, de Reijke TM, Van Tienhoven G, et al: Duration of androgen suppression in the treatment of prostate cancer. N Engl J Med 360:2516-2517, 2009.
