BRAF mutation status and its prognostic significance in 79 canine urothelial carcinomas: A retrospective study (2006-2019).

Abstract

Urothelial carcinoma (UC) is the most common tumour of the canine urinary bladder. Recently, BRAF mutation testing emerged as a diagnostic option, but its prognostic significance is unknown. This study investigates the relationship between BRAF (variant V595E) mutation status and overall survival in UC-bearing dogs. Seventy-nine patients histologically diagnosed with UC of the bladder and/or urethra between 2006 and 2019 were included in this retrospective single-centre-study. Treatment consisted of meloxicam (n= 39, group 1 'Melox'), mitoxantrone and meloxicam (+/- followed by metronomic chlorambucil; n= 23, group 2 'Chemo') or partial cystectomy followed by meloxicam +/- mitoxantrone (n= 17, group 3 'Sx'). Survival was significantly influenced by treatment (p= .0002) and tumour location (p< .001) in both uni- and multivariable analyses. BRAF mutation was identified in 51 tumours (=64.6%) and had no statistically significant influence on overall survival: MST for BRAF-negative patients 359 versus 214 days for BRAF-positive dogs (p= .055). However, in BRAF-positive dogs, survival depended significantly on type of treatment in univariable analysis: MSTs for groups 1-3 were 151, 244 and 853 days, respectively (p= .006); In BRAF-positive group 2 ('Chemo')-patients, adjuvant metronomic chlorambucil after mitoxantrone more than doubled MST compared to patients receiving mitoxantrone alone (588 vs. 216 days; p= .030). In contrast, MSTs were not significantly different in BRAF-negative patients among the three treatment groups (p= .069). Multivariate analysis of these data was not possible due to group size limitations. This study identified tumour location and treatment type, but not BRAF mutation status, as independent prognostic factors for overall survival.