New Roadmaps for Non-muscle-invasive Bladder Cancer With Unfavorable Prognosis

Abstract

About 70% of bladder cancers (BCs) are diagnosed as non-muscle-invasive BCs (NMIBCs), while the remaining are muscle-invasive BCs (MIBCs). The European Association of Urology (EAU) guidelines stratify NMIBCs into low, intermediate, and high risk for treatment options. Low-risk NMIBCs undergo only the transurethral resection of the bladder (TURB), whereas for intermediate-risk and high-risk NMIBCs, the transurethral resection of the bladder (TURB) with or without Bacillus Calmette-Guérin (BCG) immune or chemotherapy is the standard treatment. A minority of NMIBCs show unfavorable prognosis. High-risk NMIBCs have a high rate of disease recurrence and/or progression to muscle-invasive tumor and BCG treatment failure. The heterogeneous nature of NMIBCs poses challenges for clinical decision-making. In 2020, the EAU made some changes to NMIBCs BCG failure definitions and treatment options, highlighting the need for reliable molecular markers for improving the predictive accuracy of currently available risk tables. Nowadays, next-generation sequencing (NGS) has revolutionized the study of cancer biology, providing diagnostic, prognostic, and therapy response biomarkers in support of precision medicine. Integration of NGS with other cutting-edge technologies might help to decipher also bladder tumor surrounding aspects such as immune system, stromal component, microbiome, and urobiome; altogether, this might impact the clinical outcomes of NMBICs especially in the BCG responsiveness. This review focuses on NMIBCs with unfavorable prognoses, providing molecular prognostic factors from tumor immune and stromal cells, and the perspective of urobiome and microbiome profiling on therapy response. We provide information on the cornerstone of immunotherapy and new promising bladder-preserving treatments and ongoing clinical trials for BCG-unresponsive NMIBCs.

Porcine Small Intestinal Submucosa (SIS) as a Suitable Scaffold for the Creation of a Tissue-Engineered Urinary Conduit: Decellularization, Biomechanical and Biocompatibility Characterization Using New Approaches

“…It is classified as superficial in the case of non-muscle invasive bladder cancer, and as muscle-invasive 1 in the case of advanced stages. Even if 70% of bladder cancers are non-muscle-invasive and can be treated only by transurethral resection of the bladder in the case of low-risk 1, in case of intermediate- and high-risk 1, standards of care recommend the transurethral resection of the bladder, with or without bacillus Calmette–Guerin immunotherapy or chemotherapy [ 2 ]. Conversely, in the case of muscle-invasive urothelial bladder cancer (UBC), the standard treatment consists of a radical cystectomy (RC), followed by the creation of a urinary diversion using a segment of the small intestinal tract of the patient.…”

Prognostic Impact of CD36 Immunohistochemical Expression in Patients with Muscle-Invasive Bladder Cancer Treated with Cystectomy and Adjuvant Chemotherapy

“…Nevertheless, there is a clear need for novel biomarkers to identify MIBC patients who are less likely to benefit from the standard treatment and who can be offered alternative and potentially more effective therapies. In addition, in NMIBC, it could also be relevant to determine which patients may benefit from standard treatment as well as new therapeutic strategies such as immunotherapy [18]. This situation is now changing thanks to our better understanding of the molecular biology of BC, which has allowed us to identify new prognostic and predictive biomarkers that could be used in the future.…”

Preoperative Prognostic Nutritional Index and Systemic Immune-Inflammation Index for Predicting the Long-Term Recurrence-Free Survival of Patients with High-Risk Non-Muscle-Invasive Bladder Cancer After Transurethral Resection of a Bladder Tumour: A Cohort Study

“…The clinical behaviour of NMIBC is largely unpredictable, and even patients treated in accordance to EAU recommendations have a heterogeneous prognosis. Often, high-risk NMIBC patients have high rates of disease recurrence and progression to MIBC and BCG treatment failure [5]. As the highest-risk subtype of NMIBC, high-grade T1 (HGT1) BC presents an almost 40% rate of recurrence and 20% of progression at 5 years [6].…”