Longer Androgen Suppression Not Better for Intermediate-Risk Prostate Cancer

December 23, 2014

Extending the duration of androgen suppression in men with intermediate-risk prostate cancer prior to radiotherapy led to more adverse events and did not improve outcomes.

Extending the duration of androgen suppression from 8 weeks to 28 weeks prior to radiotherapy led to more sexual and endocrine adverse events and did not improve outcomes for men with intermediate-risk prostate cancer. The results of the Radiation Therapy Oncology Group (RTOG) 9910 trial suggest that an 8-week schedule of androgen suppression should remain the standard of care for these patients.

These results are published in the Journal of Clinical Oncology.

The 10-year disease-specific survival rates were 95% and 96% for the 8- and 28-week regimens (hazard ratio [HR] = 0.81; P = .45). Ten-year overall survival rates were 66% in the 8-week arm and 67% in the 28-week arm (HR = 0.95, = .62). 

The 10-year cumulative incidences of locoregional progression were 6% and 4% in the 8- and 28-week regimens (HR = 0.65; = .07).

Cumulative incidences of distant metastasis at 10 years were 6% for both therapy arms (HR = 1.07; P = .80). The 10-year prostate-specific antigen (PSA)-based recurrence cumulative incidences were 27% in both therapy arms (HR = 0.97; = .77).

“This study has significant and broad implications for best medical practices. Healthcare providers may use [the 8-week] treatment approach with confidence that its outcomes are accurate, reproducible, and generalizable to their patients,” concluded the study authors.

The open-label trial randomized 1,489 prostate cancer patients 1:1 to either 8 weeks of androgen suppression then radiotherapy with an additional 8 weeks of concurrent androgen suppression for a total of 16 weeks of therapy or to 28 weeks of androgen suppression followed by radiotherapy plus an additional 8 weeks of androgen suppression for a total of 36 weeks.

Men enrolled on the trial had no nodal or distant metastases and had an expected comorbidity survival of at least 10 years. The median age of patients was 71, and 84% of those enrolled had intermediate-risk prostate cancer.

After a median follow up of 9.4 years, 450 (30.2%) of the men died, 54 (12%) of prostate cancer.

The current trial was a clinical follow-up on the observation in animal models that prolonged androgen suppression prior to radiotherapy can improve prostate cancer outcomes.

Early grade 3 endocrine, constitutional, and sexual adverse events were higher in the 28-week are compared with the 8-week arm. The frequency of late onset adverse events were similar between the two groups.

In an accompanying editorial, Anthony V. D’Amico, MD, of the Brigham and Women’s Hospital and Dana-Farber Cancer Institute in Boston, noted that the question of whether the shorter androgen suppression regimen is sufficient or whether any androgen suppression is necessary in men with either favorable or unfavorable intermediate-risk prostate cancer is still an open question. These two questions may be at least partly answered by an additional trial, RTOG 0815. The RTOG 0815 trial will address whether 6 months of androgen suppression can reduce prostate cancer mortality in men with unfavorable intermediate-risk prostate cancer who are treated with high-dose radiotherapy, and whether high-dose radiotherapy alone is enough to minimize prostate cancer mortality. A second analysis, of the Grupo de Investigación Clínica en Oncología Radioterápica (GICOR) R17 trial will ask whether 4 months of androgen suppression along with high-dose radiotherapy can decrease prostate cancer mortality in men with intermediate-risk, unfavorable prostate cancer.

While awaiting these results, “withholding androgen deprivation therapy in men with favorable intermediate-risk prostate cancer and adding 4 or 6 months of androgen deprivation therapy to radiotherapy in men with unfavorable intermediate-risk prostate cancer are reasonable options based on the available evidence,” concludes D’Amico.