March 26, 2014
No Mortality Benefit Found for Androgen Deprivation in Early Prostate Cancer

Washington, D.C.—A new study of more than 15,000 men with early stage prostate cancer raises questions about the widespread use of androgen deprivation as the primary treatment instead of surgery or radiation.

The study, published recently in the Journal of Clinical Oncology, found that those patients receiving primary androgen deprivation therapy (PADT) did not live any longer than those who received no treatment.

Authors of the study, led by researchers from Georgetown University, suggest that risks of serious adverse events associated with the treatment, such as impaired cognition, heart disease, and diabetes, “mitigates against any clinical or policy rationale for use of primary androgen deprivation therapy in these men.” They point out that androgen-deprivation therapy has been shown to improve survival when given with radiation for later stages of disease and is considered the standard of care for men who have metastatic prostate cancer.

“This study is the most comprehensive study on the effectiveness of PADT for men who forgo radiation and surgery for their localized prostate cancer, and it tells us there is no strong reason to use it in most patients,” noted lead investigator, Arnold Potosky, PhD, a professor of oncology and director of health services research at Georgetown. “We found only a small survival benefit for primary androgen deprivation therapy compared to no therapy in men diagnosed with higher-risk localized prostate cancer.”

For the study, researchers linked cancer registries with extensive electronic medical records in three large, integrated health plans. The 15,170 study subjects, diagnosed with localized prostate cancer between 1995 and 2008, had no surgery or radiation therapy. Follow-up continued until December 2010.

Overall, PADT was associated with neither a risk of all-cause mortality (hazard ratio [HR], 1.04; 95% CI, 0.97 to 1.11) nor prostate cancer–specific mortality (HR, 1.03; 95% CI, 0.89 to 1.19) after adjusting for all sociodemographic and clinical characteristics, researchers report. PADT was associated with decreased risk of all-cause mortality only among the subgroup of men with a high risk of cancer progression (HR, 0.88; 95% CI, 0.78 to 0.97), the results indicate.

“We found no mortality benefit from PADT compared with no PADT for most men with clinically localized prostate cancer who did not receive curative intent therapy. Men with higher-risk disease may derive a small clinical benefit from PADT. Our study provides the best available contemporary evidence on the lack of survival benefit from PADT for most men with clinically localized prostate cancer,” the authors conclude.

Background in the article points out that use of PADT for early stage prostate cancer is widespread, despite the lack of randomized clinical trials to test its effectiveness. In fact, the authors note, recent studies have reported it as the second most common treatment, after radiotherapy, for clinically localized prostate cancer among older men age 65 and older.

Potosky suggested that PADT often is considered for patients who are not good candidates for, or who prefer to avoid, surgery or radiation due to their side-effects.

"Primary androgen deprivation therapy may be preferable to some men with early stage prostate cancer who would prefer to do something rather than watch and wait for further signs of progression to occur later and then need treatments," he said. “However, using PADT by itself immediately after diagnosis in the hopes of limiting cancer's progression does not extend survival, according to this study.”

Noting that his research team is using the database to examine rates of potential side effects from the treatment, Potosky added, “Given the aging American population, more men are likely to be faced with prostate cancer so it is very important to understand the whether the risks of primary androgen deprivation therapy outweigh the survival benefit. Ultimately, this is a decision for men and their doctors to make together, and we hope that our study provides some helpful information to guide these decisions.”

U.S. Pharmacist Social Connect