Why are upper tract urothelial carcinoma two different diseases?

Abstract

In the last few years growing evidence highlighted the differences between upper tract urothelial carcinoma (UTUC) and urothelial bladder carcinoma (UBC) which cannot be explained solely by their different anatomical location. The aim of this review was to summarize current progress in UTUC research and to underline the differences and similarities between UTUC and UBC by focusing on epidemiology, etiology, staging and risk factors as well as on surgical and medical management. UBC and UTUC sharing common risk factors such as smoking and aromatic amines, while aristolochic acid exposure or familiar Lynch syndrome are rather specific for UTUC. The grading of UBC and UTUC are identical, but inherent from their different anatomical locations, there are some differences between their stage classifications. As an example, in contrast to UBC where a clear recommendation for pT3 subclassification exists, in UTUC current research aims to define an adequate subclassification for pelvic pT3 cases aiming to provide a better risk stratification. The primary treatment for both UBC and UTUC is surgery. Similarly to UBC, UTUC patients at high risk of disease progression are treated by radical surgery. However, because of the inaccurate preoperative or transurethral staging of UTUC, many radical nephroureterectomies are performed unnecessarily. Preoperative prediction of pathological stage or patients’ prognosis may reduce this overtreatment by selecting patients for nephron-sparing surgery. To this end, predictive models combining histological and molecular features together with imaging data may be used. The antegrade or retrograde instillation of BCG or mitomycin C, as topical agents is feasible after conservative treatment of UTUC or for the treatment of CIS. However, the prognostic significance of lymph node positivity in UTUC seems to be similar to that of UBC, the therapeutic benefit of lymph node dissection (LND) in UTUC has not been firmly established yet. In addition, the number of lymph nodes to be removed and the sequence of lymphadenectomy also remain to be defined. Systemic neoadjuvant and adjuvant chemotherapies appear to have beneficial effect on UTUC survival, however, this has to be confirmed by large prospective studies. Due to the intensive research of the last few years, our knowledge on UTUC has been largely improved, but many questions remained to be answered. Further research on the molecular background of UTUC holds the potential to identify prognostic or predictive markers which, together with imaging and histologic data, may help to overcome the inaccuracy of ureteroscopic endoscopy and may therefore help to improve therapeutic decision-making. Further, prospective studies should confirm the benefit of LND and adjuvant chemotherapy. Considering the low incidence of UTUC, conduction of such studies is difficult and may only be performed in a multicenter setting.

Urine Cellular DNA Point Mutation and Methylation for Identifying Upper Tract Urinary Carcinoma

“…Patients of Asian ethnicity appear to have more advanced and higher-grade disease compared to others at the time of initial disease diagnosis [ 19 ]. The early detection of UTUC is still a challenge; thus, it is necessary to develop more reliable detection tools [ 20 , 21 , 22 ]. Generally, the number and frequency of mutations in different biological samples may vary depending on the grade and stage of the cancer.…”

Current Knowledge on Genomic Profiling of Upper Tract Urothelial Carcinoma

“…Considering the differences in terms of embryologic precursors, epidemiology, genetics, medical and surgical management and response to therapy, UTUC and BC should be considered two different diseases and have been previously defined as "disparate twins" [41,42].…”

The complex relationship between upper urinary tract and bladder cancer: clinical and predictive issues

“…First of all, UTUC has traditionally been considered the twin tumor of UBC, since both stem from the same tissue, i.e., the transitional lining of the urinary tract ( 2 ). Such consideration, along with its very low frequency (almost 5–10% of all UC), have resulted in outlining treatment strategies for UTUC on the basis of UBC ( 3 ).…”