Is the Success of Adaptive Therapy in Metastatic Castrate-Resistant Prostate Cancer Influenced by Cell-Type-Dependent Production of Prostate-Specific Antigen?

Abstract

AbstractProstate-specific antigen (PSA) is the most common serum marker for prostate cancer. It is used to detect prostate cancer, to assess responses to treatment and recently even to determine when to switch treatment on and off in adaptive therapy protocols. However, the correlation between PSA and tumor volume is poorly understood. There is empirical evidence that some cancer cell types produce more PSA than others. Still, recent mathematical cancer models assume either that all cell types contribute equally to PSA levels, or that only specific subpopulations produce PSA at a fixed rate.Here, we compare time to competitive release of the PSA-based adaptive therapy protocol by Zhang et al. with that of the standard of care based on continuous maximum tolerable dose under different assumptions on PSA production. In particular, we assume that androgen dependent, androgen producing, and androgen independent cells may contribute to the PSA production to different extents.Our results show that, regardless the assumption on how much each type contributes to PSA production, the time to competitive release is always longer under adaptive therapy than under the standard of care. However, in some cases, e.g., if the androgen-independent cells are the only PSA producers, adaptive therapy protocol by Zhang et al. cannot be applied, because the PSA value never reaches half of its initial size and therefore therapy is never discontinued.Furthermore, we observe that in the adaptive therapy protocol, the number of treatment cycles and their length strongly depend on the assumptions about the PSA contribution of the three types. Our results support the belief that a better understanding of patient-specific PSA dynamics will lead to more successful adaptive therapies.