The prognostic significance of variable histology in upper tract urothelial cancer (UTUC) is little understood. In this study, researchers aimed to determine whether or not UTUC cases with atypical histologies affected patient survival rates. 

In the time span from January 1995 to December 2018, they were able to identify 705 patients who had nephroureterectomy for UTUC at their institution. After controlling for the pathological stage, they used two independent multivariable Cox models to examine whether or not there was a correlation between variant histology and cancer-specific survival CSS and overall survival OS. 

A total of 47 patients (6.7%), with an increasing incidence over time (P=0.003). Variant histology and pure urothelial carcinoma groups shared similar demographic and surgical characteristics. Patients with variable histology had a higher pathological T stage and were more likely to undergo neoadjuvant chemotherapy (38% vs 15%, P<0.001). They found that having a. variant histology significantly decreased both CSS (HR: 2.14; 95% CI 1.33, 3.44; P=0.002) and OS (HR: 1.74; 95% CI 1.15, 2.63; P=0.008). Neither CSS (HR: 1.17; 95% CI 0.72, 1.89; P=0.5) nor OS (HR: 1.20; 95% CI 0.79, 1.84; P=0.4) were significantly linked with variant histology after controlling for pathological T stage. As a biomarker for high-risk disease when the pathological stage is unknown, UTUC with a variant histology is related to advanced disease and poor survival. 

Contrarily, the greater tumor stage at nephroureterectomy explains the lower CSS and OS in patients with variable histology. Therefore, the presence of atypical histology in surgical pathology does not contribute any further prognostic information beyond the stage.