Neoadjuvant Chemotherapy Before Radical Cystectomy: Why We Must Adhere?

Abstract

Aim: To provide a critical literature review on state of the art and novel strategies in the field of neoadjuvant treatments for muscle-invasive bladder cancer (MIBC). Methods: a nonsystematic literature review was performed using PubMed, Scopus and Clinical Trials.gov to retrieve papers related to neoadjuvant treatments for MIBC over the past 15 years. Prospective and retrospective studies were included. Results: Platinum-based treatment is the gold standard and mainly consists of a combination of Cisplatin with Vinblastine, Methotrexate, Doxorubicin, Gemcitabine, Adriamycin or even Epirubicin. The 5-year absolute overall survival benefit of MVAC is 5% and the absolute disease-free survival improves by 9%. CMV treatment is associated with a 10-year overall survival improving from 30% to 36% and a 16% reduction in mortality. Gemcitabine and cisplatin regimen provides complete response in 20% of cases, with non-inferior oncological outcomes compared to MVAC regimen. Recent prospective trials investigating neoadjuvant immunotherapy show high rate of complete response, from 29% with atezolizumab to 39.5% with pembrolizumab. The tyrosine kinase inhibitor pathway is being explored and could offer an interesting strategy to improve survival outcomes. Conclusions: Available evidence suggest better oncological outcomes for MIBC patients receiving neoadjuvant treatment before radical cystectomy. While MVAC remains the standard of care in cisplatin eligible patients, novel strategies are under development for cisplatin ineligible patients whereby immunotherapy seems to hold great promise.

Comparison of sequential versus concurrent chemoradiation regimens in non-metastatic muscle-invasive bladder cancer

“…In addition to the difference in disease stage between groups in our analysis, the sequential group was also significantly younger. Neoadjuvant platinum-based chemotherapy is standard-of-care for the surgical approach [ 16 ], and younger patients are more likely to be considered surgical candidates. Therefore, it could be that a proportion of sequentially treated patients were initially intended as surgical candidates, and received neoadjuvant chemotherapy in preparation for surgery, but later opted for radiation treatment as a bladder-sparing approach.…”

Characteristics of Patients Undergoing Open Radical Cystectomy for Management of Muscle Invasive Bladder Cancer in A Tertiary Centre in Egypt

“…The selection for NAC is usually based on the clinical stage with more priority to locally advanced disease (≥T3), presence of variant histology, multifocality of the tumor, the patients' co-morbidities, the baseline renal function, the delay time during diagnosis and importantly the patient preference [36,37]. The value of neoadjuvant chemotherapy has been demonstrated, Neoadjuvant cisplatincontaining combination chemotherapy (NAC) improves overall survival (OAS) (5-8% at five years), irrespective of the type of definitive treatment used [38][39][40][41]. It is unclear if patients with variant histology will also benefit from NAC [42].…”

Bladder Cancer: Immunotherapy and Pelvic Lymph Node Dissection

“…In addition, nearly half of the patients with MIBC who undergo radical cystectomy (RC) have distant metastases. MIBC is typically treated with RC following neoadjuvant chemotherapy (NAC), which has been shown to improve survival rates by reducing the chances of local recurrence and distant metastasis [ 24 , 25 ]. Neoadjuvant therapy is conducted before surgery to reduce the size of the tumor and lower the pathological stage, so as to extend patient survival and increase the success rate of radical resection [ 26 , 27 ].…”