Treatment of muscle‐invasive and advanced bladder cancer in 2020

Abstract

Bladder cancer accounts for nearly 170,000 deaths worldwide annually. For over 4 decades, the systemic management of muscle-invasive and advanced bladder cancer has primarily consisted of platinum-based chemotherapy. Over the past 10 years, innovations in sequencing technologies have led to rapid genomic characterization of bladder cancer, deepening our understanding of bladder cancer pathogenesis and exposing potential therapeutic vulnerabilities. On the basis of its high mutational burden, immune checkpoint inhibitors were investigated in advanced bladder cancer, revealing durable responses in a subset of patients. These agents are now approved for several indications and highlight the changing treatment landscape of advanced bladder cancer. In addition, commonly expressed molecular targets were leveraged to develop targeted therapies, such as fibroblast growth factor receptor inhibitors and antibody-drug conjugates. The molecular characterization of bladder cancer and the development of novel therapies also have stimulated investigations into optimizing treatment approaches for muscle-invasive bladder cancer. Herein, the authors review the history of muscle-invasive and advanced bladder cancer management, highlight the important molecular characteristics of bladder cancer, describe the major advances in treatment, and offer future directions for therapeutic development.

Hypomethylation of PlncRNA-1 promoter enhances bladder cancer progression through the miR-136-5p/Smad3 axis

“…Bladder cancer is one of the most common malignant tumors of the urogenital system. Globally, more than 430,000 individuals are annually diagnosed with bladder cancer, with nearly 170,000 mortality cases 1,2 . Depending on the degree of muscle invasion, bladder cancer is divided into nonmuscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) types.…”

“…NMIBC accounts for about 70% of newly diagnosed BC and can be treated by transurethral resection and invasive therapy. However, it often relapses and develops into MIBC 2,3 . MIBC is highly metastatic and has poor prognostic outcomes 4 .…”

Clinical Perspectives of ERCC1 in Bladder Cancer

“…Invasion of the detrusor muscle of the bladder constitutes a major contributor to disease prognosis, as 5-year survival rates reach 96% in the non-invasive population [2]. Initially 20% of patients will present with MIBC, while 15-20% of non-muscle-invasive bladder cancer (NMIBC) will eventually expand to the muscle layer [3]. Management of NMIBC is based on transurethral resection of the bladder tumor (TURBT) and intravesical therapy, like bacillus Calmette-Guérin (BCG) which leads to a 37% further reduction in recurrence rate [4].…”

“…For MIBC patients unfit for cystectomy, a bladder-preserving approach based on concurrent chemoradiotherapy can be adopted. Neoadjuvant chemotherapy (NAC) has been incorporated in current clinical practice based on Phase III studies and a meta-analysis of 11 clinical trials showing a 5-year OS benefit of 5% [3][4][5]. Cisplatin-based adjuvant chemotherapy remains a controversial issue that should be personalised in high-risk MIBC patients with extravesical or node-positive disease or positive margins [3][4][5].…”

“…Neoadjuvant chemotherapy (NAC) has been incorporated in current clinical practice based on Phase III studies and a meta-analysis of 11 clinical trials showing a 5-year OS benefit of 5% [3][4][5]. Cisplatin-based adjuvant chemotherapy remains a controversial issue that should be personalised in high-risk MIBC patients with extravesical or node-positive disease or positive margins [3][4][5]. Current data reveal a significant prolongation in progression-free survival (PFS), however the contribution to overall survival (OS) is unclear [3,6].…”