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.
I’m in a group 2 scheduling.
My oncologist told me failure to reduce PSA occurs sometime after the second round (year ).
From your reading, how long can one expect to have ADT be effective?
There is no way to predict the timing, some men never have a positive response while I know two different men who are still getting a positive effect for over 15 years! I started hormone therapy 5 years ago and I am still on treatment.
Joel
Dear Joel,
I am trying to find out if the doctor or pathologists can find out when looking into the prostate 6 months after starting hormone treatment , through a second biopsy , the type of cancer that were not affected by the hormone and are still running aggressively and growing in the prostate? Would the pathologists find the cancers that were shrunk by the hormones “lying on their sides asleep” perhaps, or some other signs indicating that they were the ones causing the reduced PSA in the blood, shrunken prostate and also they would find in there (prostate) the cancers that were unaffected by the hormones, still growing, moving and more abundant in numbers than in the original biopsy taken when the cancer was first discovered in the prostate, 6 months earlier. And can the pathologists see and identify these different types of cancers and perhaps have the drugs to kill these aggressive cancers that have grown more and more without being touched by the hormones that the patient was on during the first 6 months.
I’ve been told that the hormones does it’s full work within 6 months after starting the hormone treatment and so that is the waiting time after which time the doctor want to biopsy the prostate again to see what is left over in the prostate. He says that the ones that are not affected by the hormones during this time, is the ones that will eventually kill the patient. He also said he’d like to check the prostate 3 months after start of treatment and then 6 months after start of treatment. Then when they know what type of cancer that they are up against (ones not affected by the hormone treatment), he can determine the treatment of the prostate and also what kind of drugs needed to kill the healthy cancer that was unaffected by the hormone treatment. Do you know if this is at all possible and viable and can be realistically done to find the unaffected , possibly aggresive type of cancer in the prostate and doctors are able to treat those hormone resistant cancer? Thanks.
Wilfred,
You pose an interesting idea, but with current technology this can not be done. First, biopsies are only small samples of tissue which only tell a pathologist about the tissue that was removed in the biopsy needle. Biopsies do not tell the complete story, actually they often tell only a story on a micro-scale. I am sure that you know that men, when first diagnosed, can have prostate cancer, but their biopsy can still be negative. This is because the biopsy only shows what is in the needle, not what is in the complete prostate gland. I don’t know of any doctor who follows the protocol you have proposed. – Joel