Translation of bladder cancer molecular subtypes into clinical practice to personalize treatment decisions from non-muscle invasive to metastatic disease

Several negative pharma-industry sponsored phase III bladder cancer studies have recently been reported (DANUBE/IMvigor010/IMvigor211/ KEYNOTE361), despite exceptional long-term responses in some patients.

The purpose of this proposal is to implement molecular subtypes by RNA-sequencing and single-sample classification throughout the whole spectrum of the bladder cancer disease.

To this end, we have developed routines and introduced The Lund Taxonomy into clinical practice (UROSCANSEQ) in Southern Sweden and apply such molecular classification in the context of prospective observational and randomized trials.

To further personalize treatment, we also investigate an abbreviated clinical pathway for patients with suspected muscle invasive bladder cancer (MIBC) with MRI and integrate FDG-PET-CT evaluating treatment response during induction chemotherapy in patients with regionally metastatic disease.

We aim to clarify if molecular subtype affects risk of local recurrence in intermediate risk non-muscle invasive tumours and/or predict choice of adjuvant instillation therapy (mitomycin or gemcitabine), and if bladder cancer stage T1 with Urothelial-like subtype should be treated with BCG-instillations rather than radical cystectomy (RC).

While evaluating the new diagnostic pathway for MIBC (MRI and endodrill biopsy in local anesthesia) and FDG-PET-CT-investigations, we integrate molecular classification to further disentangle optimized use of perioperative chemotherapy in MIBC.