Poster Highlights Session: Urothelial Carcinoma - Translational Studies

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Elie W. Akl, Pier Vitale Nuzzo, Elio Adib, et al. 
The authors conclude:  Higher TMB was associated with higher incidence of irAEs in pts with mUC on ICIs. Moreover, pts with both high TMB and irAEs exhibited better response rates than those with only high TMB or irAEs, suggesting that they may provide complementary tumor and host characteristics. Further evaluation in mUC is needed to confirm this relationship between TMB, irAEs and response in a larger cohort and explore specific mutational signatures that may be associated with irAEs.
Carissa Chu, Martin Sjöström, Emily A. Egusa, et al. 
The authors conclude:  Results of this pre-clinical study suggest that sensitivity to EV is mediated by expression of NECTIN4, which is significantly enriched in luminal subtypes of bladder cancer. Downregulation of NECTIN4 leads to resistance to EV. These findings have implications for biomarker development, patient selection and the inclusion of molecular subtyping in ongoing and future EV clinical trials. Further investigation into Nectin-4 loss as a mechanism of resistance in patients treated on EV is warranted.
Hong Truong, Rania Sheikh, Aliya Khurram, Y et al. 
The authors conclude:  Deleterious germline alterations are commonly present in women with high-risk bladder cancer. The presence of germline variants in some genes, such as BRCA1/2, can guide cancer screening and risk-reducing surgeries for patients and their families. Women with high-risk bladder cancer should be evaluated for suitability of germline testing, especially those who desire preservation of uterus and ovaries at the time of radical cystectomy, to rule out the presence of P/LP variants that increase risk of future gynecologic malignancies.
Amin Nassar, Elio Adib, Elie W. Akl, et al. 
The authors conclude:  CDKN2A alteration status may serve as a predictive biomarker in patients with UC treated with ICBs. Further studies are needed to examine the mechanism of this clinical effect.
Anirban P. Mitra, Andrea Kokorovic, Tanner Miest,  et al. 
The authors conclude:  We identify and characterize FOXF1 as a novel regulatory molecule that potentially drives bladder cancer metastasis. This may be modulated through alterations in intracellular signaling and cellular adhesion. FOXF1may serve as a prognostic biomarker that can identify patients at impending risk for metastasis who may benefit from more aggressive management.