Perioperative Systemic Treatment for Muscle-Invasive Bladder Cancer: Current Evidence and Future Perspectives

Abstract

Radical cystectomy is the primary treatment for muscle-invasive bladder cancer; however, approximately 50% of patients develop metastatic disease within 2 years of diagnosis, which results in dismal prognosis. Therefore, systemic treatment is important to improve the prognosis of muscle-invasive bladder cancer. Currently, several guidelines recommend cisplatin-based neoadjuvant chemotherapy before radical cystectomy, and adjuvant chemotherapy is recommended in patients who have not received neoadjuvant chemotherapy. Immune checkpoint inhibitors have recently become the standard treatment option for metastatic urothelial carcinoma. Owing to their clinical benefits, several immune checkpoint inhibitors, with or without other agents (including other immunotherapy, cytotoxic chemotherapy, and emerging agents such as antibody drug conjugates), are being extensively investigated in perioperative settings. Several studies for perioperative immunotherapy have shown that immune checkpoint inhibitors have promising efficacy with relatively low toxicity, and have explored the predictive molecular biomarkers. Herein, we review the current evidence and discuss the future perspectives of perioperative systemic treatment for muscle-invasive bladder cancer.

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 ].…”

“…By contrast, approximately 25% of bladder cancers invade the muscle layers, and 5% have metastatic disease [ 1 , 2 , 4 , 5 , 8 , 10 ]. MIBC has a propensity to become metastatic, and, once metastatic, it is associated with a 5-year survival of only 15% [ 1 , 10 ].…”

“…MIBC has a propensity to become metastatic, and, once metastatic, it is associated with a 5-year survival of only 15% [ 1 , 10 ]. Current international guidelines recommend platinum-based neoadjuvant chemotherapy (NAC), followed by radical cystectomy (RC) or bladder preservation strategies, with chemoradiation (trimodality therapy) in select patients; adjuvant chemotherapy is also an option for select patients) [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. The most widely used platinum-based NACs include dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimens, and gemcitabine and cisplatin (GC) regimens [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ].…”

“…Current international guidelines recommend platinum-based neoadjuvant chemotherapy (NAC), followed by radical cystectomy (RC) or bladder preservation strategies, with chemoradiation (trimodality therapy) in select patients; adjuvant chemotherapy is also an option for select patients) [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. The most widely used platinum-based NACs include dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimens, and gemcitabine and cisplatin (GC) regimens [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. Although only 5% of patients are metastatic at presentation, nearly 50% of patients with MIBC, undergoing curative-intent treatment, will eventually relapse and develop metastatic disease [ 2 , 4 , 5 , 6 , 7 , 8 ].…”

“…The most widely used platinum-based NACs include dose-dense methotrexate, vinblastine, doxorubicin, and cisplatin (MVAC) regimens, and gemcitabine and cisplatin (GC) regimens [ 1 , 2 , 4 , 5 , 6 , 7 , 8 , 10 ]. Although only 5% of patients are metastatic at presentation, nearly 50% of patients with MIBC, undergoing curative-intent treatment, will eventually relapse and develop metastatic disease [ 2 , 4 , 5 , 6 , 7 , 8 ]. Despite high initial response rates, survival in the metastatic setting is 12–15 months with the most commonly used regimens, including GC, MVAC, or dd MVAC, but only 3–6 months if left untreated [ 2 , 4 , 7 , 8 ].…”