Advanced Bladder Cancer. Aspects of Diagnosis and Treatment

Sammanfattning: Treatment of bladder cancer has seen few advancements in recent decades until the introduction of checkpoint inhibitors during the last few years. Bladder cancer diagnostics have been similarly impaired and the likely advent of novel treatments in the neoadjuvant setting will require new diagnostic tools in the preoperative setting in muscleinvasive bladder cancer.This thesis evaluates three diagnostic tools with a particular focus on guiding treament before or during neoadjuvant or induction chemotherapy. Firstly, we show that presence of a single CTC with CellSearch is associated with earlier progression in patients with advanced bladder cancer as well as metastatic disease on FDG-PET-CT. A significant proportion of bladder cancer cells express EpCAM and can be detected using EpCAM-antigen based methods.Secondly, in the setting of induction chemotherapy, complete metabolic response with FDG-PET-CT is associated with survival compared to a partial response during chemotherapy followed by radical cystectomy in patients with nodepositivebladder cancer. In a similar vein, we find that the CellSearch method is not feasible in monitoring chemosensitivity due to the low sensitivity of the method. Finally, bladder cancers of the luminal-like (GU- and Uro) subtypes display improved outcomes following cisplatin-based neoadjuvant chemotherapy compared to the Ba/Sqsubtype. The methods presented in this thesis are not mutually exclusive but rather constitute reciprocal biomarkers providing information about risk of occult metastatic disease, predicted and actual response to chemotherapy at time-points wheresuch information can be clinically useful. Novel neoadjuvant treatment options for bladder cancer will likely result in a renaissance in preoperative diagnostics as alternative treatments will allow for randomized study designs for biomarkers. Future diagnostic workups will likely entail an extended suite of such biomarkers and diagnostic tools to provide all aspects of a patient’s disease.