SUO 2019: Impact of Variant Histology on Survival and Response to Chemotherapy in Patients with Upper Tract Urothelial Carcinoma

Washington, DC ( The urothelium lines the urinary tract from the renal pelvis to the urethra. While cancers may arise anywhere along the urothelium, the vast majority (90-95%) occur in the lower urinary tract (bladder and urethra) while the remainder (5-10%) occur in the upper tract (ureter and renal pelvis; UTUC).1 On the basis of their morphologically similar histology and much higher incidence of lower tract disease, evidence from patients with bladder cancer has often been used to guide the management of patients with upper tract urothelial carcinoma. However, there are important differences in both embryologic and molecular characteristics as well as management considerations between the two. These details are discussed in much more detail in a recent Center of Excellence article on UroToday but suffice to say that many details in the management of UTUC are extrapolated from bladder cancer literature. In bladder cancer, variant histologies, including micropapillary and others, have been associated with a worse prognosis. In a poster presentation at the Society of Urologic Oncology meeting, Dr. Wilson Sui and colleagues utilized the National Cancer Database to assess the association between variant histologies and survival.

The authors identified all patients with UTUC in the National Cancer Database who underwent treatment between 2003 and 2016. Patients with other cancer diagnoses or metastasis were excluded. The authors then utilized the Kaplan Meier method and Cox proportional hazard models to identify predictors of survival.

Among patients their cohort, the authors identified 27,737 patients with traditional UTUC and 1093 with variant histology. Patients who had variant histology had a higher tumor (T) and nodal (N) stage at the time of diagnosis. Thus, it is not surprising that the authors found that patients with variant histology had worse overall survival (median 30 months, 95% confidence interval 22-38 months) compared with traditional urothelial histology (median 68 months, 95% confidence interval 63-73 months). However, patients with variant histology also had worse survival when stratified by stage. In multivariable analyses, variant histology remained significantly associated with worse overall survival (hazard ratio 1.34, 95% confidence interval 1.2 to 1.5).

In this analysis, adjuvant chemotherapy appeared to be beneficial in both patients with traditional urothelial carcinoma and those with variant histology.

Results from this large dataset support previously published work demonstrating the deleterious effect of variant histology in patients with UTUC,2 mirroring the results from the muscle invasive bladder cancer literature. Given the scarcity of patients with these conditions, it will be important to maximize the information that can be derived from observational studies of these patients. Given the available knowledge consideration of treatment, intensification appears warranted.

Presented by: Wilson Sui, Department of Urology, Vanderbilt University Medical Center, Nashville, Tennessee, USA.

Written by: Christopher J.D. Wallis, MD, PhD, FRCSC, Contact: @WallisCJD on Twitter at the 20th Annual Meeting of the Society of Urologic Oncology (SUO), December 4 - 6, 2019, Washington, DC   


  1. Leow JJ, Chong KT, Chang SL, Bellmunt J. Upper tract urothelial carcinoma: a different disease entity in terms of management. ESMO Open 2016; 1(6): e000126.
  2. Mori K, Janisch F, Parizi MK, et al. Prognostic Value of Variant Histology in Upper Tract Urothelial Carcinoma Treated with Nephroureterectomy: A Systematic Review and Meta-Analysis. The Journal of urology 2019: 101097JU0000000000000523.