Introduction: While the significance of variant histology is well established in urothelial carcinoma of the bladder, less is known regarding its prognostic implications in the upper tract (UTUC). Furthermore, unlike bladder cancer, variant histology UTUC is rarely diagnosed until the time of nephroureterectomy, presenting unique management challenges. We sought to evaluate the impact of variant histology UTUC on patient survival outcomes at our institution.
Methods: After excluding patients who underwent nephroureterectomy for non-urothelial primary or metastatic tumors and benign disease, we identified 705 unique patients for analysis. All patients had surgery at Memorial Sloan Kettering Cancer Center between January 1995 and December 2018. We tested the association between variant histology and cancer-specific and overall survival using separate multivariable Cox models after adjusting for pathological stage. All analyses were performed using R version 3.6.0.
Results: 47 (6.7%) patients had variant histology on pathology. Variant histology tended to be found in patients treated in more recent years (p=0.003), reflective of evolving pathologic recognition. Other patient demographic and surgical characteristics were similar between variant histology and pure urothelial carcinoma groups. While patients with variant histology were more likely to receive neoadjuvant chemotherapy (38% vs 15%; p<0.001), they were also more likely to have a higher T stage on final pathology (p<0.001). The presence of variant histology was associated with significantly worse cancer-specific (HR 1.96; 95% CI 1.19, 3.24; p=0.008) and overall survival (HR 1.74; 95% CI 1.15, 2.63; p=0.008). After adjusting for pathological T stage, variant histology was not significantly associated with cancer-specific (HR 1.07; 95% CI 0.65, 1.79; p=0.8 ) or overall survival (HR 1.20; 95% CI 0.79, 1.84; p=0.4), indicating the strong associated influence of pathologic stage on survival in these high-risk patients.
Conclusions: The inferior cancer-specific and overall survival in patients with variant histology UTUC can be explained by the higher tumor stage on nephroureterectomy. We cannot exclude the possibility that variant histology is associated with up to a moderate survival benefit or harm; larger studies could provide a more precise estimate of risk. Source of
Funding: This research was supported by the Sidney Kimmel Center for Prostate and Urologic Cancers and funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748.