2017P - Intrinsic molecular difference between bladder and upper tract urothelial carcinomas and its impacts in treatment response

Background

Bladder Urothelial Carcinoma (BLCA) and Upper Tract Urothelial Cancer (UTUC) have been speculated to derive from similar cellular origins. However, recent studies have highlighted both molecular properties and therapeutic response were significantly different between the two entities. Therefore, we aim to further dissect and identify molecular diversity as well as clinical utility between two diseases in East Asian urothelial cancer patients.

Methods

175 BLCA and 56 UTUC patients were enrolled from the K-master consortium and subjected to NGS panels to detect major genomic aberrations.

Results

ERBB2 and ERCC2 mutations were significantly enriched in BLCA, while a mutation in BRIP1 was prominent in UTUC. Pathway analysis further discovered that the RTK pathway is highly activated in BLCA while RAS was predominant in UTUC. BLCA was distinguished by increased proliferation kinetics, whereas UTUC was distinguished by enhanced invasiveness and migratory capabilities. Furthermore, pharmacogenomic analysis revealed that TP53 mutations were significantly enriched in non-responders, while mutations in FGFR3 and KRAS were highly observed in responders. Immune checkpoint blockades demonstrated that BLCA patients exhibited relatively favorable response compared to UTUC patients and MTOR mutations were highly selective in the responder group.

Conclusions

Our results collectively suggest the significance of molecular profiling in guiding personalized treatment approach in urothelial carcinoma patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.