Genomic Alterations of Signaling and DNA Damage Repair Pathways in Non-Muscle Invasive Bladder Cancer.

The aim of the study was to demonstrate the most common genetic alterations and evaluate possible targets involving phosphatidylinositol-3-OH kinase (PIK3)/AKT/mammalian target of rapamycin (mTOR) signaling and DNA damage repair (DDR) pathways for personalized treatment in patients with non-muscle invasive bladder cancer (NMIBC). Alterations of these pathways were observed in 89.5% and 100% of patients, respectively. Among them, BARD1 was more frequently altered in low/intermediate-risk cases, but PARP4 was more frequently affected in intermediate/high-risk patients. The possible target feasibility of BARD1 and PARP4 alterations should be evaluated for personalized treatment using PARP-inhibitors in NMIBC. It is important to detect high tumor mutation burden (TMB) in patients in terms of immunotherapy.

Anna Karenina principle in personalized treatment of bladder cancer according to oncogram: which drug for which patient?

Aim: To evaluate the ex vivo efficacy of chemotherapy, immunotherapy and targeted agents with the oncogram method in patients with bladder cancer and determine the most appropriate personalized treatment agent using immune markers. Materials & methods: Bladder cancer tissues were obtained from each patient. After cultivation, cell cultures were divided into 12 groups for each patient and 11 drugs were administered. Cell viability and immunohistochemistry expression were examined. Results: A good response rate was determined to be a 23% viability drop. The nivolumab good response rate was slightly better in PD-L1-positive patients and the ipilimumab good response rate was slightly better in tumoral CTLA-4-positive cases. Interestingly, the cetuximab response was worse in EGFR-positive cases. Conclusion: Although good responses of drug groups after their ex vivo application by using oncogram were found to be higher than control group, this outcome differed on a per patient basis.

Bladder cancer primary cell cultures were shown to be effective for drug sensitivity and also able to be used ex vivo in the process of determining personalized treatment. The ex vivo efficacy of 11 different agents was evaluated with oncogram in bladder cancer cell cultures obtained from patients. Together with clinicopathological features, evaluation of drug responses detected by oncogram can provide important information for pretreatment drug selection when deciding on individualized treatment.

Can we perform frozen section instead of repeat transurethral resection in bladder cancer?

OBJECTIVE: To confirm frozen section (FS) method for muscularis propria (MP) sampling and to compare the FS method with the ReTUR section (RS) procedure to reduce needing for second resection that can cause waste of time for definitive treatment of muscle-invasive bladder cancer. METHODS: A total of 27 patients who admitted to our clinic and was performed transurethral resection of bladder tumor (TUR-BT) due to bladder tumor and had an indication of ReTUR were evaluated prospectively in the study. During the first TUR-BT procedure (as permanent section), FS examination was also performed to the patients. ReTUR was performed 2-6 weeks after the first TUR-BT procedure. RESULTS: Presences of MP were observed in 51.8% and 77.7% of FS and permanent section examinations. In the comparing of the presence of residual tumor in the methods, although 12 of 27 patients were found to have a residual tumor in FS, it was found to be in only 6 of 12 patients in RS. There was no statistical significance between FS and RS methods for MP sampling and detecting of residual tumor. CONCLUSIONS: FS was found to be a comparable method with the RS method (ReTUR procedure) for the sampling of MP and detecting of residual tumor, despite the limitations in the pathological examination FS. Especially in patients with detected residual tumor after the pathological consultation of FS during the procedure, re-resection can be a choice at the end of the first TUR-BT instead of ReTUR.