Novel and emerging approaches in the management of non-muscle invasive urothelial carcinoma

Abstract

Non-muscle invasive bladder cancer (NMIBC) has traditionally been managed with transurethral resection followed by intravesical chemotherapy and/or bacillus Calmette–Guerin (BCG) in a risk-adapted manner. These tumors commonly recur and can progress potentially to lethal muscle invasive disease. A major unmet need in the field of NMIBC is bladder preserving therapy for recurrent high-grade NMIBC after adequate intravesical BCG therapy. The current gold standard treatment for these BCG-unresponsive patients is radical cystectomy, which is associated with considerable morbidity and mortality, particularly in older and frailer patients. It is therefore critical to provide alternative treatment options with acceptable oncological outcomes. In this review we explore novel bladder-sparing treatment options including combination intravesical therapy, enhanced instillation methods, immunotherapy, gene therapy, targeted therapy, photodynamic therapy and BCG variants across the spectrum of NMIBC disease states, ranging from low grade BCG-naïve patients through to high-grade BCG-unresponsive NMIBC.

Tumor-Associated Mast Cells in Urothelial Bladder Cancer: Optimizing Immuno-Oncology

“…At presentation, about 70% of patients with UBC present with disease confined to the mucosa (stage Ta or carcinoma in situ) or submucosa (stage T1) (non–muscle-invasive bladder cancer, NMIBC), which has a good prognosis [ 1 , 2 , 3 , 4 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. NMIBC includes a diverse spectrum of diseases with a wide range of progression and recurrence rates that depend on several clinical and pathologic factors; thus, the key to improving the prognosis of NMIBC is to reduce the risk of recurrence and progression [ 3 , 4 , 7 , 9 , 11 ].…”

“…NMIBC includes a diverse spectrum of diseases with a wide range of progression and recurrence rates that depend on several clinical and pathologic factors; thus, the key to improving the prognosis of NMIBC is to reduce the risk of recurrence and progression [ 3 , 4 , 7 , 9 , 11 ]. Standard treatment of NMIBC involves transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy and/or bacillus Calmette-Guerin (BCG), in a risk-adapted manner [ 3 , 4 , 7 , 9 , 11 , 12 ]. Especially, intravesical BCG is typically reserved for high-risk patients in the first-line setting, or as an option for intermediate-risk patients [ 3 , 4 , 7 , 8 , 9 , 11 , 12 ].…”

“…Standard treatment of NMIBC involves transurethral resection of the bladder tumor (TURBT), followed by intravesical chemotherapy and/or bacillus Calmette-Guerin (BCG), in a risk-adapted manner [ 3 , 4 , 7 , 9 , 11 , 12 ]. Especially, intravesical BCG is typically reserved for high-risk patients in the first-line setting, or as an option for intermediate-risk patients [ 3 , 4 , 7 , 8 , 9 , 11 , 12 ]. Different options exist upon failure of first-line treatment, i.e., following failure of intravesical chemotherapy or BCG, and are largely dependent on the response to prior therapy [ 4 , 9 , 11 , 12 ].…”

“…Especially, intravesical BCG is typically reserved for high-risk patients in the first-line setting, or as an option for intermediate-risk patients [ 3 , 4 , 7 , 8 , 9 , 11 , 12 ]. Different options exist upon failure of first-line treatment, i.e., following failure of intravesical chemotherapy or BCG, and are largely dependent on the response to prior therapy [ 4 , 9 , 11 , 12 ]. Following BCG failure in high-risk NMIBC, the standard of care is radical cystectomy, which is associated with considerable morbidity and mortality, particularly in older and frailer patients [ 3 , 4 , 7 , 12 ].…”

“…Different options exist upon failure of first-line treatment, i.e., following failure of intravesical chemotherapy or BCG, and are largely dependent on the response to prior therapy [ 4 , 9 , 11 , 12 ]. Following BCG failure in high-risk NMIBC, the standard of care is radical cystectomy, which is associated with considerable morbidity and mortality, particularly in older and frailer patients [ 3 , 4 , 7 , 12 ]. Novel therapeutic options for patients who recur after BCG are critical in order to reduce the number of patients needing cystectomy with its associated morbidity, while maintaining acceptable oncological outcomes [ 3 , 4 , 7 , 12 ].…”