The Impact of Intermittent Androgen Suppression Therapy in Prostate Cancer Modeling

Previous studies on prostate cancer modeling under hormonal therapy successfully fit clinical serum androgen data, under the assumption that the levels of intracellular and serum androgen are similar. However, such an assumption may not hold throughout the course of treatment. In this paper, we propose a model that directly accounts for serum androgen and its interaction with intracellular androgen. We establish biological links between the model and clinical data, and discuss in detail parameter ranges and the initialization of model variables. We further investigate parameter sensitivity over time, which gauges the maximum effect of varying each parameter and allows us to fix some parameters, to increase the robustness of the parameter fitting process. By relying on the characteristics of intermittent androgen suppression therapy (IAS), we employ a two-part weighted error function for fitting. We also carry out mathematical analyses to study the dynamic aspects of the system with different androgen thresholds. We find that the proposed model shows superior forecasting ability, compared to its predecessor. Furthermore, we demonstrate the impact of androgen on the dynamics of the androgen-dependent and -independent cancer cells, which suggests the discrete description of androgen dependency may not give a realistic characterization of the cancer population. We show that IAS has certain characteristics that need to be considered for parameter estimation. Our results demonstrate that the model and the fitting scheme are viable for similar applications of prostate cancer modeling under hormonal therapy.

Case: Testicular oligometastasis from prostate cancer — Report of rare isolated recurrence after radiotherapy and intermittent androgen-deprivation therapy

Testicular oligometastasis secondary to prostate cancer is rare. We present a case where a patient with locally advanced prostate cancer was treated with high-dose external beam radiotherapy and two years of androgen-deprivation therapy, followed by intermittent androgen suppression. Three and a half years after initial diagnosis, he was found to have a painless testicular mass. Orchiectomy was performed and histopathology demonstrated metastatic prostatic adenocarcinoma. He remains in clinical remission on intermittent androgen suppression eight years following initial treatment, and over four years after presentation with testicular metastasis.