Predictive Biomarkers in the Management of Bladder Cancer: Perspectives in an Evolving Therapeutic Landscape

Abstract

Bladder cancer (BC) is a heterogeneous disease with prognosis and therapeutic strategies highly dependent on tumor grade and stage. Predictive biomarkers of therapeutic response have been studied to guide selection of intravesical and/or systemic therapy. A predictive biomarker is measured before the start of treatment and provides information on the likelihood of response to a specific therapy. Many candidate predictive biomarkers for BC have been identified, but few have been rigorously validated or distinguished from simply having treatment-agnostic prognostic capacity. Identifying predictive biomarkers tailored to therapeutic mechanism of action has considerable implications for the sequencing of therapies, as well as bladder preservation strategies in advanced disease states. We evaluate predictive tissue-based, urine-based, and serum-based biomarkers across the spectrum of non–muscle-invasive and muscle-invasive BC and preview predictive biomarkers for emerging targeted therapies.

Theories behind Bacillus Calmette-Guérin failure in high-risk non-muscle-invasive bladder cancer and update on current management

“…In one pilot study, patients with higher levels of IL-8, measured 6-h post-BCG instillation, had a lower rate of progression and recurrence. 22 Interestingly, however, higher baseline levels of IL-8 in urine and peripheral blood leukocytes correlated with a higher risk of tumor recurrence, which highlights the complexity of baseline and stimulated cytokine expression and kinetics. 22 Cytokine panels have been developed to overcome these limitations.…”

“… 22 Interestingly, however, higher baseline levels of IL-8 in urine and peripheral blood leukocytes correlated with a higher risk of tumor recurrence, which highlights the complexity of baseline and stimulated cytokine expression and kinetics. 22 Cytokine panels have been developed to overcome these limitations. One such panel is the Cytokine Panel for Response to Intravesical Therapy (CyPRIT) nomogram, which uses nine inducible urinary cytokines and was developed at the MD Anderson Cancer Center to predict the likelihood of recurrence, with 85.5 % accuracy.…”

“… 21 Tissue biomarkers such as p53 and Ki67, which are potent cell cycle regulators, have been examined as possible predictors of BCG success. 22 Studies have suggested that p53 is not predictive; however, Ki67 has been demonstrated to predict recurrence following BCG therapy. These markers were examined in panels after BCG therapy to predict progression or recurrence; however, no correlation was observed.…”

“…These markers were examined in panels after BCG therapy to predict progression or recurrence; however, no correlation was observed. 22 Immune TME is another area of interest. Pichler et al.…”

“…Studies conducted during BCG therapy and follow-up suggested that a positive FISH result at any time is suggestive of recurrence and progression. 22 Currently, no predictive biomarkers have been approved for bladder cancer by the Food and Drug Administration (FDA). This reflects the heterogeneity of NMIBC and the complexity of the mechanism of action of BCG, and the difficulty in the prediction of the elicited immune response.…”