Table 1.

Summary of notable biomarkers investigated in bladder cancer and associated study findings.

Biomarker	Studies	Key findings
p53	Stadler et al.5	p53 status did not predict recurrence after adjuvant MVAC
FGFR3 alterations	Loriot et al.14 Milowsky et al.10 Pal et al.11	Erdafitinib became the only targeted therapy approved for FGFR altered UC Dovitinib failed to demonstrate significant activity in unselected patients with mUC Infigratinib demonstrated modest activity in FGFR3 altered UC
FGFR3 mRNA overexpression	Schuler et al.16 Rosenberg et al.17	Rogaratinib is active in UC with FGFR3 mRNA overexpression
HER2	Hussain et al.26 Powles et al.29 Wulfing et al.105 Choudhury et al.30	Trastuzumab plus chemotherapy in HER2+ UC was active but toxic Lapatinib failed as maintenance therapy in HER2+ mUC Afatinib showed promising activity in a subset of mUC patients with altered HER2/ERBB3
EGFR	Petrylak et al.23 Philips et al.24 Pruthi et al.25	Gefitinib was not active in unselected patients with UC Neoadjuvant erlotinib showed promise in a small cohort of unselected patients with MIBC
PIK3CA	Munster et al.39 Seront et al.40 McPherson et al.41	Pan-isoform PI3K inhibitors show minimal or modest activity in advanced mUC with PI3K pathway alterations. Dosing was limited by significant toxicity
Molecular subtypes / gene expression profiling	Choi et al.42 McConkey et al.51 Seiler et al.43 Rosenberg et al.52 Sharma et al.53 Kim et al.54 Flaig et al.59	Basal subtype tumors benefit most from neoadjuvant chemotherapy Activated wild-type p53 gene expression signature may confer resistance to neoadjuvant chemotherapy Luminal I subtype responds to immunotherapy less often than luminal subtype II Neuronal subtype may respond well to immunotherapy The COXEN score may predict for pathologic downstaging after neoadjuvant chemotherapy
DDR gene alterations	Van Allen et al.65 Plimack et al.69 Miron et al.71 Teo et al.70 Iyer et al.72 Teo et al.75	Sensitivity to platinum-based therapy is associated with alterations of DDR genes such as ERCC2, ATM, FANCC, and RB1 DDR gene alterations are associated with benefit from immunotherapy
PD-L1	Powles et al.80 Galsky et al.81	Low PD-L1 expression in mUC predicts inferior survival on PD-1/PD-L1 inhibitors compared to platinum-based chemotherapy in the first-line
Tumor mutational burden	Balar et al.55 Galsky et al.83	High TMB is associated with high response rate and longer survival on immunotherapy in mUC
Microsatellite instability	Iyer et al.87	MSI is associated with excellent response to immunotherapy in mUC

Abbreviations: DDR = DNA damage response and repair; EGFR = epidermal growth factor receptor; FGFR = fibroblast growth factor receptor; MSI = microsatellite instability; mUC = metastatic or advanced urothelial carcinoma; adjuvant MVAC = methotrexate, vinblastine, doxorubicin, and cisplatin; PD-L1 = programmed cell death ligand 1; PI3K = phosphoinositide 3-kinase; TMB = tumor mutational burden; UC = urothelial carcinoma.