Risks of Testosterone-Lowering Treatment for Prostate Cancer Outweigh the Benefits

A large study in this month’s JAMA Internal Medicine concludes that androgen-deprivation therapy (ADT) does not extend the lives of men with early-stage prostate cancer.

The new paper, which echoes other research into the same topic, further undermines a treatment strategy that remains widespread despite “no data to support” its use and severe side effects such as depression, impotence, bone fractures, diabetes and heart disease.

“Health care providers and their older patients should carefully weigh our findings against the considerable adverse events and costs associated with primary ADT before initiating this therapy in men with clinically localized prostate cancer,” wrote the study team, which was led by Grace Lu-Yao, PhD, an epidemiologist at the Cancer Institute of New Jersey and professor of medicine at Rutgers Robert Wood Johnson Medical School.

Lu-Yao and her colleagues pulled the Medicare records of 66,717 senior men who were diagnosed with prostate cancer between 1992 and 2009, and they compared outcomes in areas of the country where ADT is more and less commonly prescribed.

Overall, after a median follow-up of 110 months, ADT was not associated any reduced chance of death from all causes‑‑or even just cancer‑‑in the 15 years after initial diagnosis.

Among patients with moderately differentiated cancers, the 15-year overall survival rate was 20.0% in areas with high primary ADT use compared to 20.8% in areas with low use (95% confidence interval (CI), −2.2% to 0.4%), and the 15-year prostate cancer survival was 90.6% in both high- and low-use areas (95% CI, −1.1% to 1.2%).

Among patients with poorly differentiated cancers, the 15-year cancer-specific survival was 78.6% in high-use areas compared to 78.5%, in low-use areas (95% CI, −1.8% to 2.4%), and the 15-year overall survival was 8.6% in high-use areas compared to 9.2% in low-use areas (95% CI, −1.5% to 0.4%).

Such findings support the conclusions of several earlier studies, which also found that ADT inflicts needless suffering on patients with localized prostate cancers and needless costs on health care systems.

Nevertheless, many doctors still prescribe the treatment for such patients. Current estimates suggest that at least quarter of all prostate cancer patients over the age of 75 are chemically castrated.

An invited editorial that accompanied the JAMA study said that the ongoing popularity of ADT treatment for localized prostate cancer is inexplicable and called the practice “a prime candidate” for inclusion in a national campaign against needless tests and treatments.

Neither the editorial nor the study paper itself recommended against the use of ADT on patients with more advanced or aggressive forms of prostate cancer. To the contrary, ADT has proven its ability both to relieve symptoms and to shrink tumors for such patients. When used in combination with radiation and other treatments, it can also help to extend life.

Studies that demonstrated ADT’s benefits against advanced prostate cancer appear to have led many doctors to begin prescribing it against less aggressive forms of the disease, initially in the absence of any evidence one way or the other and then against a growing body of evidence.