Prognostic Implications of Immunohistochemical Biomarkers in Non-muscle-invasive Blad Cancer and Muscle-invasive Bladder Cancer

Abstract

Urothelial carcinoma of the bladder (UCB) is a very heterogeneous disease and divided into invasive and non-invasive disease. In non-muscle-invasive bladder cancer (NMIBC), recurrence after transurethral resection or instillation-therapy, and progression to invasive disease are issues of concern. In muscle-invasive bladder cancer (MIBC), systemic recurrence after radical treatment is a pressing problem, as the available therapies in this setting are of limited efficacy. For both entities there are only few clinicopathological prognostic biomarkers to identify subgroups at risk to aid in decision making to whom to offer early radical cystectomy in case of NMIBC or neoadjuvant/adjuvant chemotherapy in case of MIBC to improve outcomes. Despite advances in surgery and intravesical therapy, up to 30% of NMIBC-patients suffer progression to MIBC. After cystectomy around 50% of MIBC patients suffer local or systemic recurrence and subsequently succumb to the disease. Standard features, like pathological staging and grading, are not sufficient to identify patients at risk beyond doubt. Recent advances in molecular diagnostics in combination with standard pathological features could be used to improve risk stratification of patients, guide treatment plans and ultimately improve outcomes. Immunohistochemical (IHC) analysis can detect altered regulatory pathway-products. Until now a plethora of prognostic IHC-biomarkers has been reported on in UCB, but only few have been validated and no biomarker is in routine use or recommended by guidelines. In this review we discuss the prognostic potential of the most promising IHC-biomarkers in NMIBC and MIBC with a focus on prognostication of recurrence and stage progression in NMIBC as well as recurrence-free, cancer-specific and overall survival in MIBC.