||5R01CA242559-04 Interpret this number
||University Of Michigan At Ann Arbor
||Refining Castration Use for Recurrent Prostate Cancer
Project Background: Nearly all US men diagnosed with prostate cancer have localized
disease. Most are treated, yet roughly one in three have their prostate cancer return via rising
PSA levels. A common treatment for rising PSA is castration with long-acting injectable drugs
termed androgen deprivation therapy (ADT). Understanding the best timing of ADT for these
men is important because most do not have symptoms of recurrent cancer, yet will deal with
major side effects (e.g., diabetes, osteoporosis, obesity, heart disease) in the hopes of survival
benefits. However, there is limited evidence to guide castration timing and use when it comes
to rising PSA levels after treatment. This results in vague guideline recommendations and
widespread practice variation. Whether some men can avoid castration, its side effects, or
castration-resistance without compromising survival remains unclear. Using biostatistical
models informed by real-world practice variation can refine answers to these important issues.
Project Objectives: This study will combine population-based cancer registry and electronic
record data from a national delivery system with biostatistical modeling and randomized trial
data to examine the impact of castration with ADT on progression and survival after localized
prostate cancer treatment. We will take advantage of variable castration practices to identify
populations of men that may and may not benefit from castration for recurrent prostate cancer.
Project Methods: This clinically-relevant, high impact study has three aims. Aim 1: To
examine variation in castration use after localized prostate cancer treatment. We will identify
men treated for localized prostate cancer from 2005-2015 using national cancer registry data.
We will characterize longitudinal castration practices with respect to timing, continuity, and
clinical factors (e.g., PSA, risk group, salvage radiotherapy) using national administrative
claims, pharmacy, and laboratory, as well as randomized trial data. Aim 2: To assess the
impact of castration timing on prostate cancer progression. We will identify prostate cancer
progression to castration-resistant disease among our population-based and randomized trial
data. We will use biostatistical modeling to identify castration practices associated with the
longest times to castration-resistance and survival outcomes. Aim 3: To refine populations of
men most likely to benefit from castration for recurrent prostate cancer, and when. Based on
our models and complementary datasets, we will propose criteria and timing for castration
practices to help maximize outcomes after localized prostate cancer treatment. For some men,
delaying or avoiding castration might be best, for others, earlier castration might be optimal.