PADT Appears to Offer No Mortality Benefit to Prostate Cancer Patients

Primary androgen-deprivation therapy appears not to be an effective treatment for men with clinically localized prostate cancer.

Primary androgen-deprivation therapy appears not to be an effective treatment for men with clinically localized prostate cancer.

Primary androgen-deprivation therapy (PADT), which is commonly used to treat clinically localized prostate cancer (PCa), offers no apparent mortality benefit compared with receiving no therapy at all, according to the results of a recent study.

The study, published online in the Journal of Clinical Oncology on March 17, 2014, examined data from a comprehensive cancer registry to assess the association of PADT with mortality in a cohort of 15,170 men diagnosed with clinically localized PCa between 1995 and 2008 who were not treated with curative intent therapy and who received follow-up through 2010. With more than 200,000 men diagnosed with PCa annually, the study authors note the importance of determining the long-term effect of PADT.

“In 2010, the US Food and Drug Administration notified manufacturers of ADT-injectable agents to add new warnings to their products regarding the potential risks of coronary heart disease and diabetes,” the study authors write. “Given the aging American population, it is imperative to determine whether these risks outweigh any mortality benefit from PADT.”

A recent study reported that 1 in 8 men aged 65 and older receives PADT for treatment of PCa, which is out-of-step with recommended guidelines and costs Medicare approximately $42 million per year. Additional long-term adverse events associated with PADT include impaired cognitive function, loss of muscle strength, anemia, and bone loss or fractures.

“Because men are more accepting of PADT than surgical castration, there has been remarkably widespread adoption of PADT, despite a lack of evidence for improved prostate cancer survival or overall survival,” writes Joel B. Nelson, MD, in an article accompanying the study. “This practice is even more astounding given the long-term consequences of ADT, best summarized as accelerating the aging process.”

Of the 15,170 men included in the study, 3435 received PADT within the first year. Among patients who received PADT, 58% were considered high-risk, compared with 18% in the no-PADT group.

There were 4921 deaths in the cohort during follow-up, with 1049 (32%) of the deaths attributed to PCa. Men receiving PADT were nearly twice as likely to die as were those in the non-PADT group (hazard ratio of 1.96) and nearly 3 times as likely to die from PCa (hazard ratio of 2.91). After adjusting for sociodemographic and clinical characteristics, the researchers found that use of PADT was not associated with a reduction in death from any cause (hazard ratio of 1.04) or a reduction in death from PCa (hazard ratio of 1.03).

The researchers did find a statistically significant overall mortality benefit from the use of PADT in a subgroup of patients with high risk PCa, but the benefit was small and the results should not be taken as definitive, according to the study authors.

“In summary, we found that most men diagnosed with clinically localized PCa who do not receive curative-intent therapy receive no apparent mortality benefit from PADT compared with receiving no therapy,” the authors write.

In his accompanying article, Dr. Nelson notes that other studies have indicated that early PADT for low-risk, clinically localized prostate cancer does not delay the use of second-line therapies and that PADT appears to increase the use of chemotherapy for castration-resistant prostate cancer.

“PADT is not curative,” Dr. Nelson writes. “ADT should be reserved for its established role: as palliation for metastatic prostate cancer, in men with node-positive prostate cancer after radical prostatectomy, or in combination with radiation therapy in intermediate or high-risk prostate cancer.”