Biomarkers and intermediate-high risk non-muscle invasive bladder cancer: a multivariate analysis of three different cellular pathways with pronostic implications.

To determine the presence of a group of mutations, and establish the prognostic value for recurrence and progression.

Prospective observational study. Intermediate-to-high-risk non-muscle invasive bladder cancer (NMIBC) was evaluated. Data from genetic analyses were included in a database along with clinicopathological variables of interest.

Seventy-four patients. Twenty-five (33.8%) recurred and 3 (4.1%) progressed. Median time to recurrence: 8 months (5.7-12.7). Median time to progression: 14 months (P75: 12). Mutation distribution: KRAS codon 12: one patient (1.4%), BAT25: five patients (6.8%), BAT-26: four patients (5.4%), and D2S123: 6 patients (8.1%). Arg72Pro polymorphism: 50 patients (67.6%) exhibited homozygous mutations, 23 (31.1%) were heterozygous, and 1 patient (1.4%) did not present the mutation. We found an association between presence of MSI at BAT26 and female sex (p < 0.05) and tumor stage and the TP53 Arg72Pro polymorphism. Recurrence-free survival (RFS) was significantly associated with presence of MSI at D2S123, with a HR of 5.44 for patients presenting the mutation (95% CI 1.83-16.16). On multivariate analysis, we found a statistically significant increase in risk of recurrence among patients with MSI at D2S123 (HR 5.15; p < 0.05) and more than 2 previous transurethral bladder resections (TURBs) (HR 5.07; p < 0.05) adjusted for tumor stage and grade. Harrell's concordance index revealed an accuracy of 0.74 (p < 0.05).

An association was found between presence BAT26 MSI and female sex, Arg72Pro polymorphism with tumor stage and D2S123 and more than 2 TUR procedures were associated with RFS adjusted to tumor stage and grade.

Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico. 2020 Aug 24 [Epub ahead of print]

H Garde-García, E Redondo-González, M Maestro-de Las Casas, C Fernández-Pérez, J Moreno-Sierra

Servicio de Urología, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain. ., Servicio de Urología y Unidad de Biología Molecular del Servicio de Análisis Clínicos, Instituto de Investigación Sanitaria (IdISSC), Hospital Clínico San Carlos, Universidad Complutense de Madrid, Madrid, Spain.