Cell-Level Spatio-Temporal Model for a Bacillus Calmette-Guérin-Based Immunotherapy Treatment Protocol of Superficial Bladder Cancer.

Bladder cancer is one of the most widespread types of cancer. Multiple treatments for non-invasive, superficial bladder cancer have been proposed over the last several decades with a weekly Bacillus Calmette-Guérin immunotherapy-based therapy protocol, which is considered the gold standard today. Nonetheless, due to the complexity of the interactions between the immune system, healthy cells, and cancer cells in the bladder's microenvironment, clinical outcomes vary significantly among patients. Mathematical models are shown to be effective in predicting the treatment outcome based on the patient's clinical condition at the beginning of the treatment. Even so, these models still have large errors for long-term treatments and patients that they do not fit. In this work, we utilize modern mathematical tools and propose a novel cell-level spatio-temporal mathematical model that takes into consideration the cell-cell and cell-environment interactions occurring in a realistic bladder's geometric configuration in order to reduce these errors. We implement the model using the agent-based simulation approach, showing the impacts of different cancer tumor sizes and locations at the beginning of the treatment on the clinical outcomes for today's gold-standard treatment protocol. In addition, we propose a genetic-algorithm-based approach to finding a successful and time-optimal treatment protocol for a given patient's initial condition. Our results show that the current standard treatment protocol can be modified to produce cancer-free equilibrium for deeper cancer cells in the urothelium if the cancer cells' spatial distribution is known, resulting in a greater success rate.