Identifying novel biomarkers associated with bladder cancer treatment outcomes

Abstract

Bladder cancer is a complex disease with variable prognosis. Recent investigations into the molecular landscape of bladder cancer have revealed frequent genetic alterations and molecular subtypes with therapeutic implications. Consequently, a shift toward personalized treatment of bladder cancer is underway. To this end, several biomarkers have been developed and tested in their ability to predict response to treatment in patients with bladder cancer and potentially help direct therapy. We performed a search of recently published PubMed articles using terms “biomarker,” “bladder cancer,” and the respective treatment discussed (i.e., “neoadjuvant” or “BCG”). In this review, we summarize the latest studies on novel biomarkers in bladder cancer with a focus on those intended to improve risk stratification and treatment selection.

Bladder cancer risk stratification with the Oncuria 10-plex bead-based urinalysis assay using three different Luminex xMAP instrumentation platforms

“…Multiplex assays that evaluate a composite molecular signature in urine have greater utility in detecting and monitoring BC than efforts to identify a single BC biomarker [ 6 , 7 , 10 , 11 ]. Advantages of multiplex immunoassays include increased efficiency and lower costs versus evaluating multiple analytes individually, and high-throughput capabilities that are further enhanced by using the automated features of modern instrumentation platforms [ 25 ].…”

“…Voided urine cytology is noninvasive, economical, and has high specificity for BC but also has suboptimal sensitivity, especially with low-grade and early-stage tumors [ 5 ]. Biological marker evaluation in urine samples has evolved as a noninvasive means to more effectively identify BC, stratify patient risk, and monitor treatment progress [ 6 ].…”

“…Because BC is a heterogeneous disease with varied underlying molecular signatures, no single urine biomarker currently exists that can definitively identify and track disease, or predict the likelihood of recurrence or responsiveness to treatments such as BCG [ 6 – 9 ]. Additionally, the levels of certain individual protein-based markers (e.g., nuclear matrix protein 22, NMP22, and bladder tumor antigen, BTA) are increased in urine in scenarios such as inflammation unrelated to BC [ 10 , 11 ], which can lead to false-positive interpretations.…”

The Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor for Patients with Urothelial Carcinoma of the Bladder Following Radical Cystectomy

“…Importantly, a fraction of high-grade NIMBCs do progress to become invasive. Despite clinical and histological parameters that have been associated with the risk of progression of the disease, new tools and biomarkers for more precise prognostic risk stratification are still needed for incorporation into the standard of care [ 11 ]. On the other hand, muscle-invasive bladder cancers (MIBCs) are clinically aggressive, and even after radical cystectomy [ 12 , 13 , 14 ], up to 50% of patients die of their disease.…”

“…Biomarkers such as total cholesterol levels [ 15 ] and novel biomarkers such as the neutrophil percentage-to-albumin ratio (NPAR) [ 16 ] might help in the selection of the most appropriate candidate for therapies to improve outcomes of urological cancers. Again, there are no tools that can be used to distinguish patients with lethal cancers from those that can be cured [ 11 ]. NLR evaluation could be helpful in the selection of the best candidate to a specific therapy; however, the exact role of the NLR remains controversial.…”