Men with advanced prostate cancer are typically treated with drugs that cause testosterone levels to plummet. Testosterone is a hormone that fuels growing prostate tumors, so ideally this type of treatment, which is called androgen deprivation therapy (ADT), or hormonal therapy, will stall the disease in its tracks.
For that to happen, ADT has to be administered correctly. But according to a new study, men frequently don’t get ADT at the proper dosing intervals. Too many of them get the treatments later then they should, causing testosterone levels to rise unacceptably. “Rapid increases in testosterone following delays in dosing could have implications for cancer progression,” cautions Dr. David Crawford, a urologist at the University of California San Diego, who led the study.
What the researchers did
Dr. Crawford’s team reviewed clinical data from nearly 23,000 men who were given ADT injections between 2007 and 2016. Each man’s treatment varied by how their ADT was formulated. Some types of ADT are given once a month, and others are given at three-, four-, or six-month intervals. The researchers wanted to know how many men were late on their ADT treatments, and how that would affect the amounts of testosterone in their blood.
During this research, the investigators defined “month” in two ways: either as one lasting 28 days, which is how months were defined during the clinical trials that set dosing schedules for ADT, or as a calendar month lasting 31 days. ADT was deemed late if it was given after day 28 by the first definition or after day 32 by the second definition.
What was learned
According to results, 84% of treatments were late by the first definition, meaning that subsequent treatments were given more than 28 days after the preceding ones. Of those treatments, 60% were more than a week late and 29% were late by more than two weeks.
Results obtained with the extended definition of a month followed a similar trend: 27% of injections were given more than 32 days after the preceding treatments, and of those, 13% were tardy by more than a week, and 9% were more than two weeks late.
Men who got late injections were twice as likely to have high testosterone levels as men who got the treatments on time. ADT is supposed to knock testosterone down to below 20 nanograms per deciliter of blood (ng/dL) for the set duration of therapy. The authors stressed that keeping testosterone below 20 ng/dL correlates with better survival, so clinicians should give ADT within approved dosing instructions, and monitor the hormone accordingly.
But among nearly half the men who got late injections, testosterone levels climbed over the therapeutic target. Depending on how months were defined, the levels ranged from nearly four times higher (for the 28-day month) to five times higher (for the extended month), on average, when the injections were given two weeks late.
The authors cited a number of reasons for why ADT is given late so often. Insurance companies sometimes resist financial coverage if the dosing intervals don’t correspond to a calendar month. Scheduling and transportation challenges create logistical problems for patients, and clinicians and patients alike may be unaware of how even short delays in dosing affect testosterone, since it’s rarely measured during the course of therapy.
“This is an important contribution that may explain why some men do not experience the optimal response to hormonal therapies,” said Dr. Marc Garnick, the Gorman Brothers Professor of Medicine at Harvard Medical School and Beth Israel Deaconess Medical Center, and editor in chief of HarvardProstateKnowledge.org. “It also underscores the need for continued testosterone monitoring. Finally, as we indicate, a one-month dose should be repeatedly given every 28 days, and a three-month dose repeatedly given at 12 weeks. On a personal preference level, my general practice is to use the four-week treatments as opposed to longer-acting formulations, which are associated with more frequent departures from optimal testosterone levels.”