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Abstract
Introduction. The selection of the optimal pharmacological treatment for urothelial cancer (UC) depends on the clinical and morphological characteristics of the tumor as well as the somatic status of the patient. Predictive biomarkers that can reduce overtreatment of patients and identify cases that will not respond to chemotherapy are currently lacking in medical practice.
Aim. This study aims to retrospectively evaluate recurrence-free and overall survival in patients with UC based on fibroblast growth factor receptor (FGFR) alterations and neo- and/or adjuvant drug therapy.
Materials and Methods. Molecular genetic testing was performed on 24 samples of surgical material obtained after radical cystectomy in patients with muscle invasive bladder cancer (MIBC). All formalin-fixed and paraffin-embedded tissue samples were subjected to manual microdissection of tumor cells. Nucleic acids (DNA and RNA) were extracted from the sections using phenol-chloroform extraction. The presence of mutations in the FGFR3 gene and translocations involving the FGFR2 and FGFR3 genes in the samples tested was determined using a proprietary test system developed based on highly sensitive methods - digital droplet PCR and real-time PCR.
Results. The group of clinically significant mutations/translocations of FGFR genes included 6 cases (25.0 %): mutations in the FGFR3 gene accounted for 4 cases and 2 cases of FGFR3 translocation. The second group included patients without FGFR2/3 mutational burden (n = 18). Neoadjuvant therapy (NT) was given in 50.0 % of cases in the FGFR aberration group and in 72.2 % of cases in the non-mutation group (p = 0.362). Adjuvant therapy (AT) was administered in half of the cases in each patient group (p = 1.0). The recurrence rate of MIBC with NT did not depend on mutation status and did not affect DFS and OS. When evaluating the relationship between DFS and AT using Cox regression, postoperative therapy alone was associated with a 4.687-fold reduction in the risk of MIBC recurrence (HR 0.213, 95 % CI: 0.062-0.734; p = 0.014), independent of clinical and morphological indicators, including FGFR aberration status.
Conclusion. This retrospective analysis of the efficacy of perioperative drug therapy did not show any dependence of aberration rates in the FGFR2/3 genes on clinical and morphological parameters or oncological survival.
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