Risk stratification of upper tract urothelial carcinoma (UC) is central to current clinical guidelines on postoperative surveillance after management with radical nephroureterectomy (RNU). While low-grade upper tract urothelial carcinoma (LG-UTUC) is generally classified as low risk and lacks significant association with cancer-specific mortality, urothelial recurrence in the bladder is not uncommon. Here we describe recurrence patterns and predictive risk factors for urothelial recurrence after RNU for LG-UTUC in order to improve surveillance strategies and treatment outcomes.

METHODS:

Retrospective review of 474 RNUs at our institution from February 2010 to August 2021 identified 87 patients with LG-UTUC. Clinical, pathologic, recurrence, and survival data were obtained. Descriptive statistics, Kaplan-Meier survival curves, Mantel-Cox log rank testing, and logistic regression modeling were utilized to examine the cohort and compare risk factors for any and early recurrence of urothelial malignancy following RNU.

RESULTS:

Among 87 RNUs for LG-UTUC, mean age at surgery was 71.8 years, and most patients were male (74.7%), white (90.8%), and current/former smokers (90.9%). 50.6% had history of UC of the bladder. Median overall survival (OS) was 97.9 months (mos) (Figure 1). Thirty-nine patients (44.8%) with LG-UTUC experienced any UC recurrence over a mean follow up of 34.0 mos. Recurrence was diagnosed at median 7.5 mos post-RNU, and median recurrence-free survival was 14.4 mos. 69.2% of recurrences were low-grade and all but two initially recurred in the bladder. Multivariable analysis of demographics, surgical factors, and tumor characteristics demonstrated that current smoking (OR 4.0, p=0.04) and tumor multifocality (OR 3.5, p=0.04) were associated with recurrence at any time point (Table 1). Tumor multifocality was also significantly associated with early urothelial recurrence within 6 months of RNU on unadjusted analysis.

CONCLUSIONS:

LG-UTUC is at risk of recurrence in the bladder; however, development of metastatic disease and cancer-related mortality is very rare after definitive management with RNU. Current smoking and tumor multifocality are independently associated with recurrence of UC after RNU and may inform surveillance strategies.