Abstract
Urothelial carcinoma of the bladder (UCB) and upper tracts (UTUC) is often regarded as one entity and is managed generally with similar principles. While neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC) is an established standard of care in UCB, strong evidence for a similar approach is lacking in UTUC. The longest survival is seen in patients with complete response (pT0) on pathological examination of the RC specimen, but impact of delayed RC in nonresponders may be detrimental. The rate of pT0 following NAC in UTUC is considerably lower than that in UCB due to differences in access and instrumentation. Molecular markers have been evaluated to try to predict response to chemotherapy to reduce unnecessary treatment and expedite different treatment for nonresponders. A variety of potential biomarkers have been evaluated to predict response to cisplatin based chemotherapy including DNA repair genes (ATM, RB1, FANCC, ERCC2, BRCA1, and ERCC1), regulators of apoptosis (survivin, Bcl-xL, and emmprin), receptor tyrosine kinases (EGFR and erbB2), genes involved in cellular efflux (MDR1 and CTR1), in addition to molecular subtypes (Basal, luminal, and p53-like). The current state of the literature on the prediction of response to NAC based on the presence of these biomarkers is discussed in this review.
Highlights
Urothelial carcinoma is the second most common genitourinary cancer in the United States, with an annual incidence for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) of 81,190 and 3820, respectively [1]
While other studies [32,63] have not shown any correlation between ERCC1 expression and pathologic response, which may be due to small sample size, Hemdan et al reported significantly prolonged survival among patients with ERCC1-negative tumors who underwent neoadjuvant chemotherapy (NAC) compared to observation (HR 1.77, p = 0.002), an improvement which was not identified in ERCC1-positive tumors [66]
Invasive urothelial carcinoma is associated with a high mortality rate; increasing use of NAC has continued to improve the Overall survival (OS) in this population
Summary
Urothelial carcinoma is the second most common genitourinary cancer in the United States, with an annual incidence for urothelial carcinoma of the bladder (UCB) and upper tract urothelial carcinoma (UTUC) of 81,190 and 3820, respectively [1]. In 2003, level I evidence in favor of neoadjuvant chemotherapy (NAC) prior to radical cystectomy was published for UCB, the benefit was modest [2]. The largest benefit was observed in complete responders to NAC with patients demonstrating no residual tumor (pT0) on radical cystectomy specimens. Patients with residual MIBC or nodal involvement after NAC are at high risk of recurrence and it is possible that patients who were nonresponders had progression of disease while receiving NAC. Identifying patients who are unlikely to respond could allow better selection of early cystectomy or enrollment in clinical trials. We sought to summarize the available literature and evidence regarding the benefit of pT0 in both UCB and UTUC, as well as the clinical and molecular predictors for the complete response to NAC
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