A study by Yu et al., of men with a rising PSA after failed radical prostatectomy or radiation therapy who were placed on intermittent androgen deprivation therapy (IADT) indicated that the length of their first “off cycle” correlates with their expected time to developing castrate resistant prostate cancer (CRPC) and to their prostate cancer-specific mortality.
In this study the subject men had an initial “on” treatment cycle of 9 months before going into an “off cycle.” Their PSA levels were assessed once a month during the off-treatment period. The men then returned for a second cycle of ADT when their PSA reached 1 ng/ml for men previously treated with radical prostatectomy or 4 ng/ml for men previously treated with radiation therapy. Originally, 100 men served as subjects, but only 72 of the 100 met the PSA criteria and were considered in the statistical analysis.
For the complete length of the study, all the men remained on an intermittent schedule until they developed castrate resistant prostate cancer (CRPC), which in this study was defined as two consecutive PSA increases while also being castrate and on ADT.
The study found that in men with an “off cycle” of = 40 weeks in the first off-treatment cycle could expect to have a briefer period of time to onset of CRPC (hazard ratio [fusion_builder_container hundred_percent="yes" overflow="visible"][fusion_builder_row][fusion_builder_column type="1_1" background_position="left top" background_color="" border_size="" border_color="" border_style="solid" spacing="yes" background_image="" background_repeat="no-repeat" padding="" margin_top="0px" margin_bottom="0px" class="" id="" animation_type="" animation_speed="0.3" animation_direction="left" hide_on_mobile="no" center_content="no" min_height="none"][HR] = 2.9) and death (HR = 3.8) after adjusting for age, stage, grade, and PSA at diagnosis. Yu et al. conclude that, “In patients who completed the first cycle of [intermittent ADT], a duration of the first off-treatment interval of = 40 weeks defines a subset of patients at higher risk of CRPC and death. Conversely, patients with an off-treatment interval of >40 weeks have a significantly better long-term prognosis.’
A major issue with this study is its failure to disclose the beginning PSA values of the men as they began their first “on cycle” of treatment. Without this being disclosed, we cannot draw any conclusions. The significant factor that might be contributing to the earlier onset of CRPC could in fact be directly linked to the initial PSA levels and not the IADT schedule. Studies like this also come up short as they provide no information or guidance as to how best determine the most advantageous schedule for IADT, including at what PSA number to both start and stop a cycle.
Additionally, this study assumes a parallel to a post surgical PSA of 1.0 to a post radiological PSA of 4.0. I have no idea where these assumptions have come from and if they are valid.
The study also fails to recognize the recent data developing about the potential harms that might come about from the use of early hormone therapy. ADT increases the risk for both coronary and metabolic disease which can, by itself, be fatal. Starting an “on cycle” with a PSA as low as what was used in this study strikes me as being negligent.
Joel T Nowak, MA, MSW[/fusion_builder_column][/fusion_builder_row][/fusion_builder_container]
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