Bladder cancer: shedding light on the most promising investigational drugs in clinical trials

Abstract

Introduction: Urothelial cancers (UC) include tumors of the bladder, upper tract, and proximal urethra. Bladder cancer (BC) arises from urothelial cells lining the bladder and accounts for 90-95% of UC. BC is responsible for approximately 500,000 new cases and has a dismal prognosis with 200,000 deaths annually globally. However, immune checkpoint inhibitors (ICIs) and antibody-drug conjugates are rapidly changing the treatment landscape. Novel therapies are building on this success and are being intensively investigated in clinical trials. Areas Covered: This paper examines the clinical trial data by searching Medline through January 2021 and clinicaltrials.gov and conference proceedings from the latest ASCO and ESMO meetings. We summarize the emerging data from clinical trials and offer insights into mechanisms of novel agents, nuances in clinical trial designs, and future directions. Expert Opinion: Approval of multiple ICIs, Enfortumab Vedotin (EV), Erdatfitinib and switch maintenance strategy with Avelumab, represent major advances in metastatic disease. ICI agents and EV are well poised to move forward for treating the early stages of bladder cancer. Finally, molecular characterization of the tumor offers hope for personalized treatment approaches.

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

“…Urothelial bladder cancer (UBC) is a common disease with high morbidity and mortality rates, accounting for around 2.1% of all deaths due to cancer per year [ 1 , 2 , 3 , 4 , 5 , 6 , 7 ]. As the high rate of recurrence and the need for long-term surveillance greatly increased the economic burden of UBC patients, exploring optimized and personalized therapeutic modalities against UBCs is a rapidly evolving and expanding field in adjuvant and definitive settings [ 4 , 8 , 9 ]. Tumoral depth of invasion and detrusor invasiveness are the most significant variable for progression, recurrence, and survival in UBC [ 6 ].…”

“…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 ]. 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 ].…”

“…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 ].…”