Variant histology in upper tract carcinomas: Analysis of the National Cancer Database

Upper urinary tract malignancies are relatively uncommon, with the majority representing urothelial carcinoma (UC). Variant histology (VH) is rare but has been increasingly shown to confer worse prognoses, and standardized approaches to treatment for upper tract cancers with VH have not been established. Our study aimed to analyze outcomes amongst various treatment modalities for upper tract malignancies based on VH subtype. Additionally, we stratified mortality outcomes associated with the upper tract tumors based on their primary location in the renal pelvis (RP) versus ureter.

The National Cancer Database was queried for patients who were diagnosed with upper tract malignancy of the RP or ureter from 2005 to 2016. Populations were grouped based on tumor location (RP vs. ureter) and substratified based on tumor histology (UC vs. VH). Cox regression (CR) was used for multivariable survival analysis.

A total of 63,826 patients with upper tract malignancies met inclusion criteria: 36,692 (57.5%) cases involving the RP and 27,134 (42.5%) cases involving the ureter. VH was noted in 2.5% of all tumors with the squamous cell variant being the most common subtype (62.5%). VH presented with higher stage, increased mortality, and higher proportion of metastatic disease relative to UC.  Patients with VH were less likely to undergo surgical intervention and more likely to receive radiation or adjuvant chemotherapy. Neoadjuvant chemotherapy was not associated with tumor downstaging for VH. On multivariable CR, receiving definitive surgical excision improved survival for patients with any VH, and chemotherapy improved survival for patients with renal VH. On subanalysis of CR by VH subtype, survival benefits for surgery were significant for adenocarcinoma, neuroendocrine, and squamous in a renal location and adenocarcinoma, neuroendocrine, sarcoma, and squamous in a ureteral location. Additionally, benefits of chemotherapy were significant for adenocarcinoma in a renal location and neuroendocrine in a ureteral location.

Patients with upper tract VH are more likely to present at advanced stages and experience higher mortality rates when compared to pure UC. Generally, survival benefits are seen with either surgical excision or chemotherapy for renal VH and with surgical excision for ureteral VH, but mortality rates for these treatment modalities differ amongst specific subtypes.