One of our biggest disputes around hormone deprivation (ADT) concerns the question of scheduling. Traditionally, ADT involved staying on the therapy drug forever. However, ADT causes significant side effects that negatively impacts both the quality of life as well as posing potential significant medical problems.

Over the last five or so years there has been a move to alter the schedule of using ADT drugs allowing men to have a resting period “off” the drugs (Intermittent ADT). Most men experience an improvement in their quality of life during theses “off” periods and there is also evidence that some of the negative medical problems are also mediated. However, it remains unclear if there is a significant difference in the eventual outcomes of the different dosing schedule, with some doctors expressing concern that intermittent use of ADT drugs are much less effective.

There has also been a small group of doctors have also experimented scheduling ADT drugs based on strict monitoring of testosterone levels (T-Based) where on and off dosing was reliant upon careful monitoring of the testosterone levels with the goal of always keeping the testosterone level below a predetermine level (ideally <20 ng/dl).Questions and debates have been raised about the comparative efficacy of theses different scheduling paradigms.A recent paper in by Blumberg et. al., published in Urology has suggested that intermittent and T-based regimens are less likely to be associated with early onset of castration resistances when compared to traditional continuous therapy.This large study evaluated 1,617 men with prostate cancer who were treated with ADT monotherapy at the Kaiser Permanente Southern California Cancer Registry between January 2003 and December 2006. All the men included in the study received only monotherapy ADT.The subjects were divided into one of three groups:Group 1: These men received calendar-based dosing in which the men were continuously dosed every 3, 4 or 12 months depending upon the formulation of drugs they received.Group 2: These men received intermittent dosing which depended entirely on the men’s PSA numbers.Group 3: These men received T-based dosing regimens which relied on starting and stopping therapy on the testosterone levels.This study, a retrospective analysis of data from 692 of the men who met the study criteria showed that:Men in the T-based group (group 3) showed a significantly lower relative risk of treatment failure (hazard ratio [HR] = 0.65, P = 0.02) compared to those in Group 1 which was the calendar based dosing paradigm.Men in the intermittent based dosing group (group 2) demonstrated a trend toward a lower relative risk treatment failure (HR = 0.80, P = 0.3) compared to those in the calendar group (group 1), but the differences were not statistically significant.Among the other variables analyzed, the researchers found that a Gleason score > 8 (HR = 2.05, P = 0.01) and a pretreatment PSA level > 20 ng/ml (HR = 2.00, P < 0.01) were associated with a higher risk of treatment failure.According to the researchers, “During the time period studied, T-based and intermittent dosing regimen of LHRH agonist had lower rates of early castrate resistance compared with standard calendar dosing, based on measurements for early androgen resistance.”It is possible to conclude that the use of ADT monotherapy should be based on an intermittent schedule using T levels to determine the actual schedule. However, the authors did not follow up with the subjects to evaluate the most important question, what was the over all effect of these dosing schedules on survival.Joel T Nowak, M.A., M.S.W.