Cancer in the urinary bladder afflicts around 3000 persons per year in Sweden, most often older men and smokers. Despite being a quite common cancer type it is an understudied cancer type considering the burden to society and health outcomes [1].

To patients with superficial cancer limited to the mucosa of the urinary bladder, the prognosis is good, but once the tumor has grown into the muscle-layer of the bladder wall, the 5-year survival is only around 50%. This life-threatening form of bladder cancer is treated with radical cystectomy (removal of the bladder) and neoadjuvant (pre-operative) cisplatin-based combination chemotherapy aiming to shrink the tumor and eradicate micro-metastatic disease. While adding chemotherapy to surgery does increase survival, the increase is modest with 5% absolute survival increase, and only about a third of the cases show a visible pathologic response in the bladder. Pathologic response is a very good surrogate of outcome, but we currently have no predictive tools to identify responders beforehand. Such a prediction tool would have two main uses: Patients who do not obtain any response could be spared the toxicity associated with cisplatin-based chemotherapy regimens, and patients with a predicted   complete response could potentially keep the bladder with higher quality of life at no additional risk of death.

At the molecular level, our research group has developed a molecular classification system which separates bladder cancer into five distinct subtypes depending on the gene expression and differentiation state of the cancer cells [2]. These subtypes are molecularly as different from each other as cancers from different organs are, but the classification has not yet been translated into clinical use. Thus, although they exist as five distinct types with vast differences at all molecular levels, bladder cancers are still treated as a single disease and new knowledge about their molecular heterogeneity has not yet resulted in benefit to the patients.

In this project we hypothesize that the different molecular subtypes of bladder cancer probably do not respond to systemic therapy in the same way. We will therefore analyze molecular profiles obtained from diagnostic tissue samples before treatment and identify response biomarkers in the context of an optimal subtype-classification [3].

References

1. Carter, A. J.; Nguyen, C. N. A comparison of cancer burden and research spending reveals discrepancies in the distribution of research funding. BMC Public Health 2012, 12.

2. Höglund, M.; Bernardo, C.; Sjödahl, G.; Eriksson, P.; Axelson, H.; Liedberg, F. The Lund taxonomy for bladder cancer classification – from gene expression clustering to cancer cell molecular phenotypes, and back again. The Journal of Pathology 2023, 259, 369–375.

3. Aramendía Cotillas, E.; Bernardo, C.; Veerla, S.; Liedberg, F.; Sjodahl, G.; Eriksson, P. A versatile and upgraded version of the LUNDTAX classification algorithm applied to independent cohorts 2023. BioRxiv, 2023.