Use of Neoadjuvant Chemotherapy for High-Risk Upper Tract Urothelial Carcinoma - Beyond the Abstract

Survival for patients with high-risk Upper Tract Urothelial Carcinoma (UTUC) has remained poor over the last two decades despite advances in cross sectional imaging and endoscopy. While a significant survival advantage has been demonstrated with use of neoadjuvant chemotherapy for urothelial carcinoma of the bladder, few studies have explored the use of neoadjuvant chemotherapy in the treatment of patients with high-risk UTUC. The primary rationale for the use of neoadjuvant chemotherapy is pathologic tumor downstaging and eradication of micrometastatic disease that may be missed by conventional staging. In addition, for patients with UTUC, use of chemotherapy applied in a neoadjuvant– as opposed to an adjuvant – setting is indicated given the significant incidence of chronic kidney disease following radical nephroureterectomy. 

Recently, two studies have shown that patients with UTUC had significantly lower pathologic stage distribution of their primary tumors and improved survival following neoadjuvant chemotherapy. These studies are promising but were published a number of years ago, and no further literature has been published on this important topic. In light of this, we set out to validate the use of neoadjuvant chemotherapy by using a contemporary cohort of patients with UTUC who underwent radical nephroureterectomy (RNU) at The Johns Hopkins Hospital from 2003-2017. We compared patients who underwent neoadjuvant chemotherapy prior to RNU versus patients who only underwent RNU alone. Between these two cohorts, we evaluated a number of parameters including baseline characteristics and pathologic variables such as pathologic tumor stage.

We observed that patients treated with neoadjuvant chemotherapy had significantly lower prevalence of invasive tumors (≥pT2) and a significant reduction in the prevalence of advanced tumors (≥pT3). Patients treated with neoadjuvant chemotherapy also had a 9.4% complete remission rate which was defined as the absence of any malignant specimen on surgical resection. Due to short follow up, we are still waiting for survival data to mature. Preliminary survival data shows that 88% of patients treated with neoadjuvant chemotherapy were still alive at the 1-year time point compared to 83% of patients who had RNU alone (p=0.9).

Our paper updates the limited literature on the use of neoadjuvant chemotherapy to treat patients with UTUC. While survival data is needed, these results suggest that multimodal approaches combining neoadjuvant chemotherapy and RNU may be beneficial in treating patients with high-risk UTUC. Further prospective trials are underway to evaluate this treatment paradigm and potentially improve survival outcomes for this cohort of patients. 


Written by:
Ross Liao, Mohit Gupta, MD, and Philip Pierorazio, MD of Johns Hopkin Hospital Baltimore, MD | Twitter: @RossLiao @drphil_urology

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