№79. UROLOGICAL CANCERS DEVELOPEMENT

Relevance. Bladder cancer is the 3rd among all tumors by the number of genetic mutations. Implemention of new techniques in routine clinical practice give us an opportunity to identify genetic changes, open up the prospects for effective treatment depending of the tumor type.

Aim. The purpose of this article is to review the current understanding of the mechanism of bladder cancer and the possibility of its implementation in clinical practice.

Description of the object of study. The article provides an overview of the statistics, pathogenesis of the development and treatment of bladder cancer.

Findings. Bladder cancer is a tumor with a large number of gene mutations. Modern technologies have allowed to establish and structure genetic events arising in the development of bladder cancer. These point gene alterations can serve as potential targets for assessing the prognosis of the course of the disease, as well as the selection of targeted antitumor therapy. Determination of the mutational load and genetic sequencing are methods as close as possible to the understanding of practical specialists.

Keywords: urothelial carcinoma, muscle invasive bladder cancer (MIBC), non-muscle invasive bladder cancer (NMBC), FGFR3, TP53, oncogene, mutation load, genetic profiling.

In connection with the introduction of modern targeted and immuno-oncological antitumor drugs into wide clinical practice, the question remains of increasing the effectiveness of treating metastatic forms of cancer using a combination of these drugs with surgical removal of the primary tumor and metastatic lesions. Our article reviewed the key trials on this problem in the main metastatic tumors of the genitourinary system.

Cytoreductive operations have been well studied in renal cell carcinoma. According to the results of many trials, the benefit in survival is shown when removing the primary tumor and metastatic lesions, however, the patient’s selection for this type of intervention in combination with systemic treatment is influenced by the prognosis, which depends on various risk factors.

The question of cytoreductive operations in urothelial carcinoma is significantly less studied. However, the available trials have demonstrated a positive role on the oncological results of the removal of primary and metastatic tumors.

Also several retrospective studies confirm the benefit from cytoreductive prostatectomy and the removal of metastases in oligometastatic prostate cancer.

Keywords: cytoreductive operation, metastasectomy, renal cell carcinoma, urothelial cancer, prostate cancer.

The results of recent studies will dramatically change the approaches to the treatment of metastatic renal cell carcinoma (mRCC) in the near future. Most of the changes will affect the first-line of therapy, which will lead to the emergence of a new endpoint and the goal of therapy such as a treatment-free survival. Patients on the treatment will be able to receive therapy for a long time, and developing complete responses will not require switching to the second-line. Invading new therapeutic options will increase the oncologist’s arsenal, allow to personalize therapy, plan several lines from the first visit of the patient, and increase the total duration of treatment.

Keywords: metastatic renal cell carcinoma, systemic therapy, nivolumab, ipilimumab, avelumab, axitinib, pembrolizumab, PD-L1 expression, cytoreductive nephrectomy.

Prostate cancer (PCa) is one of the leading causes of death from cancer in men. Violation of the cell life cycle is crucial for the development and progression of prostate cancer. Taxanes, including docetaxel and cabazitaxel, are microtubule stabilizing agents that block mitotic division and lead to apoptosis. Some past studies have shown relatively good tolerability of taxanes and promising efficacy in various regimens. In previous studies, an increase in the survival rate was observed with the use of taxanes in metastatic (both hormone-sensitive and castration-resistant) and mesoprotective (including as part of the combined treatment) process. This article describes modern approaches including new antiandrogenes to the use of this class of drugs in the treatment of metastatic prostate cancer.

Keywords: prostate cancer, cabazitaxel, docetaxel, abiraterone, enzalutamide.

Targeted therapy and immune checkpoint inhibition drastically changed the perspectives of patients with urological cancers. Monotherapy with checkpoint inhibitors is on different stages of clinical investigation, determined by particular tumor prevalence. In this article authors describe current situation in the field of new therapies and express an opinion on their development.

Keywords: immunotherapy, targeted therapy, checkpoint inhibitors, urothelial cancer, renal cell cancer.

Gastric cancer is one of the leading causes of death from cancer in the world. This review provides information on groups of genes that are most frequently subjected to genetic disorders: receptor tyrosine kinase genes; cell cycle regulator genes; Hippo signaling cascade genes; genes of WNT/beta-catenin, Hedgehog and TGF-beta/SMAD4 signaling pathways; chromatin modification genes (ARID1A, MLL1-MLL4, DOT1L, EZH); genes encoding cell adhesion and cytoskeleton molecules (CDH1, FAT1-FAT4, CTNNA1-CTNNA2, RHOA). The known data on the possible role of these genetic disorders in the gastric adenocarcinoma pathogenesis is described in detail and the data on the possibilities of developing targeted drugs are presented.

Keywords: gastric adenocarcinoma, gastric cancer, carcinogenesis, genetic disorders, signaling cascades, oncogenes, tumor growth suppressor genes.

Aim. To assess the significance of immunohistochemical diagnostics in determining the molecular biological properties of tumors and predicting the results of surgical treatment in patients with locally advanced colon cancer of older age groups.

Material and methods. The results of surgical treatment of locally advanced colorectal cancer in patients of different age groups were evaluated. The clinical significance of immunohistochemical markers for predicting long-term results was studied.

Results. The most significant risk factors for postoperative complications were identified. The prognostic significance of such immunohistochemical markers as: the index of proliferative activity of cancer stem cells (ALDH+Ki-67+) and the receptor for chemokines CXCR4 was established.

Conclusion. The use of immunohistochemical diagnostics provides additional information about the potential of tumor malignancy, which is necessary for a reasonable choice of surgical tactics.

Keywords: locally advanced colorectal cancer, immunohistochemical diagnosis, molecular profile of the tumor, geriatric patients.

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