Abstract
The clinical course for both early and late stage Bladder Cancer (BC) continues to be characterized by significant patient burden due to numerous occurrences and recurrences requiring frequent surveillance strategies, intravesical drug therapies, and even more aggressive treatments in patients with locally advanced or metastatic disease. For these reasons, BC is also the most expensive cancer to treat. Fortunately, BC offers an excellent platform for chemoprevention interventions with potential to optimize the systemic and local exposure of promising agents to the bladder mucosa. However, other than smoking cessation, there is a paucity of research that systematically examines agents for chemoprevention of bladder cancers. Adopting a systematic, molecular-mechanism based approach, the goal of this review is to summarize epidemiological, in vitro, and preclinical studies, including data regarding the safety, bioavailability, and efficacy of agents evaluated for bladder cancer chemoprevention. Based on the available studies, phytochemicals, specifically isothiocyanates such as sulforaphane, present in Brassicaceae or “cruciferous” vegetables in the precursor form of glucoraphanin are: (a) available in standardized formulations; (b) bioavailable- both systemically and in the bladder; (c) observed to be potent inhibitors of BC carcinogenesis through multiple mechanisms; and (d) without toxicities at these doses. Based on available evidence from epidemiological, in vitro, preclinical, and early phase trials, phytochemicals, specifically isothiocyanates (ITCs) such as sulforaphane (SFN) represent a promising potential chemopreventitive agent in bladder cancer.
Highlights
Bladder cancer (BC) is the fourth most common cancer in men in the United States and eighth most common cause of cancer death [1]
BC originates primarily in the transitional cell epithelium that lines the inner surface of the bladder and is directly exposed to urine, which is known as transitional cell carcinoma (TCC) [4]
NMIBC is typically treated with endoscopic transurethral resection (TUR), which may be followed by an intravesical therapy, depending on the extent of the cancer, tumor grade and the presence of carcinoma in situ
Summary
Bladder cancer (BC) is the fourth most common cancer in men in the United States and eighth most common cause of cancer death [1]. 7075% of newly diagnosed BCs are non-muscle invasive www.impactjournals.com/oncotarget (NMIBC), previously referred to as “superficial” BC, while 25-30% of tumors upon initial diagnosis are muscle invasive (≥ clinical stage T2) [4]. NMIBC is typically treated with endoscopic transurethral resection (TUR), which may be followed by an intravesical therapy, depending on the extent of the cancer, tumor grade and the presence of carcinoma in situ. Given the high risk of recurrence and disease progression, careful surveillance after cancer removal by TUR via cystoscopy is currently the standard clinical practice. Intravesical therapies with Bacillus Calmette-Guerin (BCG) or chemotherapeutic agents (e.g., mitomycin C), delivered via a urethral catheter, are used to prevent or delay recurrence and progression after TUR [7]. Overall survival is poor once distant metastasis (~15% 5 year survival) has occurred [15] with stage being the most important prognostic factor of BC [16]
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