Diagnostic and Prognostic Implications of FGFR3, TP53 Mutation and Urinary Biomarkers in Urothelial Carcinoma in Pakistani Cohort

<b>Background:</b> Urothelial carcinoma (UC) presents with clinically heterogeneous disease. There is an emerging need to explore the prognosis of non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Therefore, we aimed to explore the prognostic value of FGFR3 and TP53 mutations and protein expression and to investigate the diagnostic utility of urine cytology and Xpert bladder cancer monitor (BCM) assay in UC. <b>Materials and Methods:</b> A prospective cross-sectional study was conducted in a cohort of 73 Pakistani patients. Cystoscopy, biopsy, tissue diagnosis, UC grade, and stage followed by immunohistochemistry (IHC) and genotyping were recorded. Voided urine samples were also collected for urine cytology and Xpert BCM. Statistical analysis was performed using SPSS version 26.0. A <i>p</i>-value ≤ 0.05 was considered statistically significant. <b>Results:</b> In our selected patients, the majority were males who had smoking history and the common symptom was hematuria. Our findings suggest FGFR3 IHC expression is strongly linked to low-grade NMBIC (<i>p</i> ≤ 0.01). p53 IHC expression supports the findings of the UC grade (<i>p</i> ≤ 0.01). A highly significant association (<i>p</i> < 0.001) was observed between FGFR3 protein expression and underlying mutations. Pro72Arg polymorphism (<i>p</i> = 0.04) was found to be significantly correlated with p53 IHC findings. While comparing cystoscopy with cytology and Xpert BCM, the sensitivity was found to be 85.7% and 58.5%, respectively. <b>Conclusions:</b> The integrated approach of IHC with genotyping could improve risk stratification and guide personalized management strategies. Moreover, as cytology is less sensitive to diagnose UC, especially low-grade tumours, Xpert BCM can be used as a promising diagnostic test for both primary and recurrent BC settings.