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Synchronous metastases in upper tract urothelial carcinoma has doubled in the last 10 years: an analysis of staging and treatment trends using the National Cancer Database
Brendan M. Browne, MD, David Canes, MD, Matthew Moynihan, MD, Kristian Stensland, MD.
Lahey Hospital and Medical Center, Burlington, MA, USA.

Introduction:
Upper tract urothelial carcinoma (UTUC) is a relatively rare malignancy, accounting for approximately 5,000 new diagnoses per year. Nephroureterectomy (NU) and endoscopic treatments achieve good outcomes in organ-confined disease, but survival is significantly lower in patients with metastases. Chemotherapy can also be employed for high-risk or systemic disease, with increasing attention to neoadjuvant use as post-NU CKD may be limiting. The National Cancer Database (NCDB), which captures 75% of all cancer diagnoses in the US, allows analysis of diagnosis and treatment trends that may not be apparent in smaller single-center series.
Methods:
Using the NCDB, we identified all patients diagnosed with urothelial carcinoma of the renal pelvis or ureter between 2004-2013. Data comprising baseline tumor (e.g. staging), patient (e.g. age, gender) and facility (e.g. region) factors were extracted from the database. Treatment data including surgery and chemotherapy were also extracted. Data on timing of chemotherapy were available after 2005. Comparisons were conducted using the chi-squared test.
Results:
A total of 48,845 cases of UTUC were included and analyzed. Over the ten-year capture period of the NCDB, the gender and age distribution of new UTUC diagnoses were stable at 60% male, with median age at diagnosis 72 years. The proportion of patients diagnosed with cTa/cT1 increased over ten years (60% to 67%, p<0.001), and the proportion of ≥cT2 decreased from 35% to 28%, (p<0.001). However, presentation with metastatic disease (clinical M1) rose from 4.6% to 8.9% (p<0.001). The rate of nephrectomy/nephroureterectomy was stable at 59% for ≥cT2 and 51-52% for <cT2 disease. Similarly, the rate of adjuvant therapy was stable at 11% (19% for ≥cT2). The rate of neoadjuvant chemotherapy, however, increased from 0.8% in 2006 to 2.3% in 2014 for all stages, and from 0.6% to 4.4% in ≥cT2 disease (p<0.001). Overall, patients with ≥cT2 were more likely to undergo NU than patients with <cT2 (60.8% v. 52.6%, p<0.001). Similarly, ablation/minor excision was more common in <cT2 tumors than ≥cT2 (18.3% v. 3.7%, p<0.001). Patients older than 65 years were more likely to not receive surgery (16.1% vs 11.6%, p<0.001) or to undergo ablation/excision (12.4% v. 8.6%, p<0.001) compared with younger individuals, which remained stable. Men were more likely than women to undergo surgery of any kind (84.3% v. 81.4%, p<0.001) by a small margin.
Conclusions:
While UTUC demonstrates largely stable basic demographic trends over the past ten years, the rate of synchronous metastatic disease has increased despite a decrease in ≥cT2 diagnoses. An apparent concomitant rise in utilization of neoadjuvant chemotherapy and persistent utilization of adjuvant chemotherapy is notable. Observations from any administrative dataset are hypothesis drivers, and potential for reporting bias exists. Further investigation into etiology of the increased rate of metastases is warranted, as this is the first such report. Additionally, variables predicting management, including age and gender, and subsequent survival, as well as comparative effectiveness of UTUC surgical and adjuvant therapies are forthcoming.


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