Aim. To perform comparative analysis of functional outcomes of repeat kidney resection and radical nephrectomy in patients with local cancer recurrence after previous organ-sparing surgeries.

Materials and methods. Data on 64 patients who underwent surgical treatment at the Oncourology Department of the N.N. Blokhin National Medical Research Center of Oncology between 2000 and 2022 due to local kidney cancer recurrence after previous nephron-sparing surgeries were retrospectively and prospectively included in the study. Among these, 37 (57.8 %) patients underwent repeat kidney resection (treatment group) and 27 (42.2 %) patients underwent radical nephrectomy (control group). The groups were matched in demographic and clinical characteristics (р >0.05). Median diameter of recurrent tumor in the treatment and control groups was 2.5 and 3.0 cm, respectively (95 % confidence interval 2.0–3.0 cm; Q₁–Q₃ 2.4–4.0 cm). This difference was statistically significant (р = 0.012), but not clinically. Median follow-up duration was 35 (3–131) months (Q₁–Q₃ 13–57 months).

Results. Repeat nephron-sparing surgeries correlated with lower decrease in kidney function compared to organ-resecting surgical treatment. In the early postoperative period, decrease in calculated glomerular filtration rate per the CKD-EPI formula compared to baseline after re-resection and nephrectomy was 16 and 32 % (р = 0.010); long-term, it was 8 ± 41 and 45 ± 22 % (р <0.001), respectively. Complication rates in the groups were similar: 21.6 and 29.6 %, respectively (р = 0.563).

Conclusion. For local kidney cancer recurrence, repeat resection promotes preservation of kidney function without increased complication rate.

Background. The most important problems in improvement of treatment outcomes in patients with renal cell carcinoma (RCC) are search and validation of molecular markers for its early diagnosis and prognosis. Genes suppressing distant metastasizing but not affecting the primary tumor are called metastasis suppressors. Study of these genes and their products not only improves understanding of the mechanisms of tumor progression, but has practical value for diagnosis, prognosis, and establishment of new molecular targets for antitumor therapy. One of such genes is KISS1 with its product kisspeptin (KISS1) protein.

Aim: comparative evaluation of KISS1 concentration in blood serum of practically healthy persons and patients with renal cancer; analysis of correlations between the marker’s level and clinical and morphological characteristics of the disease.

Materials and methods. 140 patients with RCC (88 men, 52 women) aged between 29 and 82 years were included in the study. Among them, clear cell RCC was diagnosed in 84 patients, papillary in 38, chromophobe in 18. The control group was comprised of 40 healthy persons of matched age and sex. Pre-treatment KISS1 concentration in blood serum was measured using a direct enzyme immunoassay kit (Kisspeptin 1 – KISS1, Cloud-Clone Corp., USA).

Results. Median serum KISS1 concentration in the control group was 51.7 pg/mL which was significantly lower than in the total RCC patient group – 243.6 pg/mL (p <0.0001). ROC analysis of diagnostic value of serum KISS1 level was performed both for the total RCC group and for each of its three histological types. In the total group the sensitivity of the test was 75 %, specificity – 80 % (AUC 0.877; 95 % confidence interval (CI) 0.827–0.927; optimal cut-off level 130.8 pg/mL; р <0.0001). For clear cell RCC, both sensitivity and specificity were 85 % (AUC 0.941; 95 % CI 0.902– 0.979; cut-off 141.8 pg/mL; p <0.0001). In non-clear cell RCC types, sensitivity of this marker was only 58 % while the specificity remained 80 % (for papillary RCC AUC 0.787; 95 % CI 0.684–0.889; cut-off level 135.5 pg/mL; p <0.0001, and for chromophobe RCC AUC 0.774; 95 % CI 0.617–0.929; cut-off level 132.1 pg/mL; p <0.001). KISS1 level increased with disease progression: it is significantly higher at more advanced stages above stage I, and in patients with distant metastases compared to those without metastases. Higher serum KISS1 level is also observed in patients with poorly differentiated high-grade (per Furhman) clear cell RCC and papillary RCC (G₃–G₄) than in those with well differentiated low-grade (G1–G2) tumors.

Conclusion. KISS1 level is significantly increased in patients with RCC compared to healthy controls and is a stagedependent marker of this disease. It has relatively high diagnostic sensitivity and specificity (both 85 %) for the most frequent histological type of RCC – clear cell RCC. Thus, clinical significance of kisspeptin in RCC requires further investigation.

Background: The extent of tumor shrinkage has been deemed a predictor of survival for advanced/metastatic renal cell carcinoma (RCC), a disease with historically poor survival.

Objective: To perform an exploratory analysis of overall survival (OS) by tumor response by 6 mo, and to assess the efficacy and survival outcomes in specific subgroups.

Design, setting, and participants: CLEAR was an open-label, multicenter, randomized, phase 3 trial of first-line treatment of advanced clear cell RCC.

Intervention: Patients were randomized 1:1:1 to lenvatinib 20mg orally daily with pembrolizumab 200 mg intravenously once every 3 wk, lenvatinib plus everolimus (not included in this analysis), or sunitinib 50 mg orally daily for 4 wk on treatment/2 wk of no treatment.

Outcome measurements and statistical analysis: Landmark analyses were conducted to assess the association of OS with tumor shrinkage and progressive disease status by 6 mo. Progression-free survival, duration of response, and objective response rate (ORR) were analyzed by the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk subgroup and by the presence of target kidney lesions. Efficacy was assessed by an independent review committee as per Response Evaluation Criteria in Solid Tumors version 1.1.

Results and limitations: Landmark analyses by tumor shrinkage showed that patients enrolled to lenvatinib plus pembrolizumab arm with a confirmed complete response or >75 % target-lesion reduction by 6 mo had a 24-mo OS probability of 91.7 %. A landmark analysis by disease progression showed that patients with no progression by 6 mo had lower probabilities of death in both arms. Patients with an IMDC risk classification of intermediate/poor had longer median progression-free survival (22.1 vs 5.9 mo) and a higher ORR (72.4 % vs 28.8 %) with lenvatinib plus pembrolizumab versus sunitinib. Similarly, results favored lenvatinib plus pembrolizumab in IMDC-favorable patients and those with/without target kidney lesions. Limitations of the study are that results were exploratory and not powered/stratified.

Conclusions: Lenvatinib plus pembrolizumab showed improved efficacy versus sunitinib for patients with advanced RCC; landmark analyses showed that tumor response by 6 mo correlated with longer OS.

Patient summary: In this report of the CLEAR trial, we explored the survival of patients with advanced renal cell carcinoma by assessing how well they initially responded to treatment. We also explored how certain groups of patients responded to treatment overall. Patients were assigned to cycles of either lenvatinib 20 mg daily plus pembrolizumab 200 mg every 3 wk or sunitinib 50 mg daily for 4 wk (followed by a 2-wk break). Patients who either had a ‘‘complete response’’ or had their tumors shrunk by >75 % within 6 mo after starting treatment with lenvatinib plus pembrolizumab had better survival than those with less tumor reduction by 6 mo. Additionally, patients who had more severe disease (as per the International Metastatic Renal Cell Carcinoma Database Consortium) at the start of study treatment survived for longer without disease progression with lenvatinib plus pembrolizumab than with sunitinib.

Background. According to the clinical guidelines from the leading Russian and international societies, treatment of patients with metastatic renal cell carcinoma is based on combination use of immune and targeted drugs. In December of 2022, the first Russian analogue of immune-oncological drug pembrolizumab with trade name Pembroria® was registered in Russia.

Aim. To evaluate safety of the biosimilar, as well as register its effectiveness in the form of objective response estimation in accordance with the RECIST v.1.1 (Response Evaluation Criteria in Solid Tumors version 1.1) criteria. The article presents the results of the first experience of using Pembroria® in real clinical practice. Two clinical observations are presented demonstrating effectiveness and safety of the biosimilar.

Materials and methods. At the clinic of the N. Lopatkin Scientific Research Institute of Urology and Interventional Radiology – branch of the National Medical Research Radiology Center, 21 patients with clear cell renal cell carcinoma who did not previously receive systemic antitumor treatment underwent immunotarget therapy with Pembroria® and a targeted agent: lenvatinib (20 mg/day orally) or axitinib (10 mg/day orally).

Results. The analysis of effectiveness considering short follow-up periods was performed in 18 patients. Median follow-up period was 6 (2–13) months and objective response rate was 50 %, in 28 % of cases stable disease was observed. Survival rates were not evaluated due to short observation time.

Conclusion. Use of Pembroria® medication in patients with metastatic renal cell carcinoma in real clinical practice showed high objective response rate with acceptable toxicity level. No new, previously not described adverse events were registered during Pembroria® administration.

Background. Currently, for patients with localized PC, intact erectile function, and low risk of extracapsular extension radical prostatectomy (RP) with nerve-sparing (NS) technique is indicated. The proven method of intraoperative control for the presence of positive surgical margin is the study of fresh frozen sections.

Aim. To evaluate the method of intraoperative histological examination (cito-histology) in NS RP.

Materials and methods. A prospective clinical study was conducted to examine fresh frozen sections in laparoscopic NS RP. Between February of 2021 and May of 2022, 90 patients diagnosed with prostate cancer underwent laparoscopic NS RP performed by the same surgeon. The patients were divided into 2 groups: group A (n = 40) included patients who underwent laparoscopic NS RP and intraoperative histology; group B (control group) (n = 50) included patients who underwent standard laparoscopic NS RP. Rapid histological and final histological examinations of all removed samples were carried out at the City Clinical Hospital No. 1 named after N.I. Pirogov by one pathologist. The presence of tumor tissue in a stained resection margin was considered positive surgical margin.

Results. Oncological processes in macrosamples obtained by intraoperative histology were observed in 32 (80 %) patients, of which primary positive surgical margin was found in 9 (22.5 %) patients. Conversion of (cito) positive surgical margin status into final negative surgical margin was observed in 4 (10 %) patients. Conversion of the surgical margin status of (cito) negative to positive was observed in 1 (2.5 %) patient due to the targeted examination of the area of interest, and not the entire surface of the prostate. Overall 2-year survival in groups A and B was 100 % and 96 %, respectively; cancer-specific 2-year survival was 100 % and 100 %, respectively. Depending on the pathological group, recurrence-free 2-year survival was: group A (pT2) – 90 %; group B (pT2) – 92 %, group A (pT3) – 91.3 %; group B (pT3) – 77.3 %.

Conclusion. The proposed method of intraoperative histological examination allows to determine the presence and location of positive surgical margin, which indicates to the surgeon the necessity of additional tissue removal in the neurovascular bundle area, reduces the technical and economic burden on pathology department compared to other methods of rapid histological examination, and reduces contraindications to performing the NS technique in RP especially in the intermediate-risk group.

Multiparametric magnetic resonance imaging (mpMRI) has an indisputable advantage in diagnosis of local recurrences of prostate cancer (PCa). Even though mpMRI has been shown to be very informative for detection of local PCa recurrences, high variability in its application and interpretation remains. Experts from the European Society for Urogenital Radiology (ESUR), the Imaging Committee of the European Association of Urology (ESUI), and several members of the PI-RADS committee developed a unified report system called Prostate Imaging Recurrence Reporting (PI-RR) to measure the risk of local recurrence of PCa in men who have had radical prostatectomy and radiation therapy and are being followed up. The principles of mpMRI that form the basis of PI-RR are well known and are stated in the PI-RADS v.2.1 guidelines, which have proven their diagnostic efficiency. The PI-RR system has the potential to become an important tool for improving communication between specialists involved in the process of PCa diagnosis and treatment, for optimizing treatment strategy in patients with local PCa recurrence, and for improving survival rates in patients with PCa after specialized anticancer treatment.

Background. In literature, data on the results of robot-assisted radical prostatectomy (RARP) in patients after transurethral resection of the prostate (TURP) are contradictory.

Aim. To evaluate surgical, functional, and oncological outcomes of RARP after TURP.

Materials and methods. At the Urology Center of the Mariinsky Hospital (Saint Petersburg), RARP was performed on 410 patients. Among them, 28 (6.8 %) patients (1st group) previously underwent TURP due to infravesical obstruction. Among them, 18 (64.3 %) patients were diagnosed with prostate cancer after pathomorphological examination of the tissue resected during TURP, and on them RARP was performed on average 3.2 months later. In 10 (35.7 %) patients, prostate cancer was diagnosed during transrectal biopsy due to increased prostate-specific antigen level; on them RARP was performed on average 42.0 months after TURP. The following parameters were evaluated: operative time, time of bladder neck reconstruction and urethrovesical anastomosis formation, blood loss volume, tumor pathological stage, Gleason score, surgical margin status, rates of urine continence and preservation of erectile function.

Results. Mean operative time was higher in the 1^st group compared to the 2^nd: 210 ± 36 min versus 180 ± 25 min (р <0.0001). In the 1^st group compared to the 2nd, reconstruction of bladder neck was necessary more frequently (82.1 % versus 10.7 %; р <0.0001), urethrovesical anastomosis took longer time (32 ± 2.3 min versus 24.5 ± 3.1 min; р <0.0001), mean blood loss volume was higher (240 ± 39 mL versus 170 ± 32 mL; р <0.0001). Frequencies of positive surgical margin were 14.3 and 10.7 % respectively in the 1^st and 2^nd groups (р = 0.840). Frequencies of all complications were 28.6 and 21.4 %, respectively. Severe complications (≥IIIb grade per the Clavien classification) were observed in 2 (7.1 %) patients in both groups. Frequency of anastomosis stricture after surgery was significantly higher in the 1st group: in 2 (7.1 %) and 1 (3.6 %) case, respectively (р <0.05). In the 1^st group, total urinary continence was achieved in 14 (50.0 %), 20 (71.5 %), 22 (78.5 %) and 25 (89.3 %) patients at early and 3-, 6and 12-month follow-up after RARP; in the 2^nd group, it was achieved in 18 (64.3 %), 22 (78.6 %), 24 (85.7 %) and 26 (92.9 %) patients in the same follow-up periods. After 6 and 12 months, in the 1^st group among 15 (53.6 %) patients with normal initial erectile function, satisfactory erectile function was preserved in 46.7 and 93.3 % of patients; in the 2^nd group among 19 (67.8 %) patients, in 57.8 and 94.7 % patients, respectively.

Conclusion. RARP after TURP is a relatively complicated surgical intervention with long operative time and high blood loss volume. However, functional and short-term oncological outcomes of RARP in these patients do not differ at 12 months.

Background. The current need for optimization of salvage treatment methods is dictated by the growing expansion of indications for radical prostatectomy in many centers in the developed countries of the world.

Aim. To evaluate the effectiveness, toxicity, and technical characteristics of high-dose rate brachytherapy in treatment of local prostate cancer (PCa) recurrences after radical prostatectomy.

Materials and methods. Between January 2015 and December 2020, salvage high-dose rate brachytherapy was performed in 17 patients at the Russian Scientific Center of Roentgenology and Radiology for local recurrence of PCa after radical prostatectomy. All patients underwent multiparametric magnetic resonance imaging of the pelvis at the stage of primary diagnosis in order to determine macroscopic tissue component in the prostate bed area. To rule out regional and distant metastases, all patients underwent positron emission tomography with ¹⁸F- or ⁶⁸Ga-labeled prostate-specific membrane antigen. All patients included in the study underwent perineal biopsy of the prostate bed and seminal vesicles.

Results. Median follow-up in the treatment group was 35.7 (24–54) months. Overall survival was 100 %. Prostatespecific antigen-specific survival was 88.2 %. There were no local recurrences of PCa in the treatment group. In patients with local PCa recurrence, significant predictors of treatment failure were the presence of clinically extremely high risk of progression at initial diagnosis (p = 0.003), development of biochemical relapse up to 24 months after main treatment (p = 0.001), and increased blood level of prostate-specific antigen above 10 ng/mL during registration of biochemical relapse (p = 0.002).

Conclusion. High-dose rate brachytherapy is a safe and effective salvage treatment for local recurrence of PCa after radical prostatectomy. In addition to the brachytherapy technique, the diagnostic stage is also of great importance providing visualization of the exact location of tumor recurrence.

Radical cystectomy remains the “golden standard” for treatment of patients with invasive bladder cancer. The operation is a technically complex surgical intervention after which there are various complications, including gastrointestinal complications such as intestinal obstruction, peritoneal adhesive disease and others. The use of extraperitoneal access for radical cystectomy with an extraperitoneal location of the artificial bladder in carefully selected patients reduces the number of abdominal postoperative complications and improves results in the immediate postoperative period. A literature review is presented which outlines the results of using extraperitoneal approach in comparison with other options for surgical approaches when performing radical cystectomy with intestinal bladder plastic surgery. It is noted that extraperitoneal access during this operation was previously used by Russian urologists.

Aim. To perform pharmacoeconomic evaluation of chemotherapy schemes GC (gemcitabine, cisplatin) and GemCarbo (gemcitabine, carboplatin) in comparison with immunotherapy drugs atezolizumab, pembrolizumab or avelumab in patients with locally advanced or metastatic urothelial carcinoma.

Materials and methods. Pharmacoeconomic cost–effectiveness analysis, sensitivity analysis in context of changes of initial model parameters were performed.

Results. Literature data analysis allows to make a conclusion of better clinical effectiveness and safety of immunotherapy drugs compared to chemotherapy in patients with urothelial carcinoma. Cost of medications was significantly lower for platinum-based chemotherapy (103,625.61 rubles for GC and 88,733.63 rubles for GemCarbo) compared to a course of immunotherapy (950,092.39 rubles for atezolizumab, 953,340.21 rubles for pembrolizumab, 1,328,999.43 rubles for GC + avelumab). However, the cost of treatment of complications arising during platinum-based chemotherapy was more than 20-fold higher than cost of treatment of immunotherapy complications: 578,853.02 rubles versus 15,336.78– 26,994.52 rubles). Cost–effectiveness analysis favored atezolizumab for which cost–effectiveness ratio was 53,230.69 rubles for 1 month of patient’s life. Atezolizumab had better value than standard 1st line GC chemotherapy by 10,671.80 rubles, as well as immunotherapy courses using pembrolizumab by 9,697.57 rubles and GC + avelumab by 10,824.66 rubles. The highest costs were observed for GemCarbo chemotherapy course: it is 18,522.82 rubles more expensive than atezolizumab course. Sensitivity analysis performed for the cost–effectiveness ratio showed stability of the developed model in regards to increased cost of atezolizumab course up to +18 % and decrease in overall survival with this course up to –15 %.

Conclusion. Atezolizumab is a clinically effective and economically justified option for treatment of adults with locally advanced or metastatic urothelial carcinoma and PD-L1 expression ≥5 % in the healthcare system of the Russian Federation.

According to summary autopsy data, the incidence of accidentally detected neoplasms of the adrenal glands is 6 %. Computed tomography performed for other reasons shows adrenal gland lesions in 4 % of cases. In diagnostic strategy for adrenal gland lesions, the most important factors to consider are hormonal activity and malignant potential. Moreover, absence of clinical manifestations for long periods of time and their mildness frequently lead to underestimation of the seriousness of the situation. Therefore, surgical treatment can be accompanied by multiple negative consequences. Literature describes cases accompanied by hypertensive crises which subsequently turned out to be hormonally inactive adenomas or adrenocortical carcinoma. The article describes a patient in whom hormonal activity masked an extremely rare benign tumor.

Kidney cancer is the 3rd most common disease in oncological urology. In 4–10 % cases, tumor thrombus of the inferior vena cava is diagnosed. In literature, single-digit number of cases of organ-preserving surgical treatment of patients with kidney cancer complicated by tumor thrombus is described. The article presents a rare clinical case of synchronous bilateral morphologically different kidney cancer with tumor thrombus in the left renal vein, perirenal segment of the inferior vena cava, pyeloureteral segment stone in the right ureter.

As new methods of focal treatment become more and more popular in the treatment of prostate cancer, cases of ineffective treatment are gradually revealed, which require correction in the volume of surgical or other method of treatment.

The article describes experience of radical treatment of prostate cancer in case of local recurrence of the disease after ultrasound ablation of the prostate.

A 58-year-old man who 1 year ago had undergone high-intensity focused ultrasound (HIFU) hemiablation of the left prostatic lobe using Focal One robotic platrform due to prostate adenocarcinoma was examined 1 year after the operation. Total prostate-specific antigen blood level was 5.45 ng/mL. The patient underwent a control transrectal biopsy of the prostate from 12 cores, which revealed recurrence of the disease in the contralateral (previously untreated) prostate lobe. The patient underwent robot-assisted radical prostatectomy. Operative time was 80 minutes. The patient was discharged from the hospital on the 7^th day with no postoperative complications. The urethral catheter was removed on the 6^th day after control CT cystography. Erectile function and urine retention were preserved. Total prostate-specific antigen level after 6 months of follow-up did not exceed 0.02 ng/mL.

Robot-assisted radical prostatectomy is an effective and safe method of treatment in patients with recurrent prostatic adenocarcinoma after HIFU if performed by a surgeon with sufficient experience in robot-assisted surgery.

It is established that prostate-specific membrane antigen (PSMA), despite its name, is expressed in many tissues other than the prostate gland, both within physiological conditions and in various pathological processes. Additionally, apart from prostate cancer, other malignant tumors are characterized by increased PSMA expression which, according to many authors, is associated with neoangiogenesis. These factors are reflected in the results of PSMA-radioligand imaging and require comprehensive approach to image interpretation including evaluation of computed tomography and magnetic resonance semiotics. In addition, rare cases of distant visceral prostate cancer metastasis in the form of solitary lesions also should be considered during interpretation of the results of radiologic imaging including positron emission tomography/computed tomography.

We present two clinical cases in which positron emission tomography/computed tomography revealed solitary foci of pathological [18F]PSMA-1007 uptake outside the areas of typical metastatic spread (with exception of advanced disease)of prostate cancer, specifically in the stomach wall and the left cerebellar hemisphere. In the first case histologicalexamination results revealed a metachronous low grade neuroendocrine tumor of the stomach, in the second case a metastatic lesion of the cerebellum was diagnosed as part of the underlying disease.

The question of optimal times and indications for radiotherapy (adjuvant or salvage) after surgical treatment of prostate cancer remains unanswered. Therefore, studies of this problem are essential and important for clinical practice. The article evaluates the effectiveness of adjuvant radiotherapy compared to salvage radiotherapy in the context of recurrence-free survival and associated adverse events. In 3 randomized clinical trials and meta-analysis, adjuvant radiotherapy did not show improved recurrence-free survival compared to salvage radiotherapy. The choice between adjuvant and salvage radiotherapy should be based on individual patient history and the risk of recurrence. Delayed radiotherapy can help some patients to avoid excessive treatment and associated adverse events.

Worldwide, prostate cancer has remained one of the most common malignant neoplasms among men and it is accompanied by high mortality rates. Standard methods for diagnosing prostate cancer have limited sensitivity and specificity, unnecessary biopsies are often performed, and the risk of overdiagnosis of the disease and overtreatment of patients is high. The review considers diagnostic and prognostic biological markers of prostate cancer proposed in recent years. Theoretical foundations for the use of new biomarkers are analyzed. The characteristics and practical significance of biomarkers of various groups (immunohistochemical, molecular and genetic, prostate specific antigen-associated, volatile organic metabolites) are presented. The need for further large-scale scientific research in the field of biomarker application in prostate cancer, criteria for their selection and evaluation are described. The introduction of modern diagnostic and prognostic markers into real clinical practice opens up new opportunities for improvement of prostate cancer diagnosis, individual prognosis, and rationalization of treatment strategy.

In clinical practice, immune checkpoint inhibition based on the use of antibodies against PD-1 (programmed death 1), PD-L1 (programmed death-ligand 1) and CTLA-4 (cytotoxic T-lymphocyte-associated antigen 4) is actively used for treatment of kidney cancer. However, objective response to monotherapy with these drugs is observed only in 9–24 % of patients, and combinations with other anticancer drugs in most cases cause severe adverse reactions. At the same time, there is an increased risk of toxic liver damage, immune-dependent pneumonitis, and rash. Therefore, it is necessary to search for new methods of immunotherapy, the most promising of which is the method of viral mimicry based on epigenetic stimulation of retroelement expression. Double-stranded retroelement transcripts activate antiviral interferon response that induces apoptosis of tumor cells. To achieve this, inhibitors of DNA methyltransferase, deacetylase and histone methyltransferase are used which have been successfully applied to treat various malignant neoplasms. In the experiment, DNA methyltransferase inhibitor 5-aza-2-deoxytidine (decitabine) effectively inhibited clear cell renal cell carcinoma cells proliferation which indicates their potential in treatment of kidney cancer. However, similarly to other neoplasms, activation of retroelements in renal cell carcinoma serves as initiator of the tumor process as it leads to increased expression of oncogenes, inactivation of tumor suppressors, and genomic instability. Therefore, the method of viral mimicry requires a differentiated approach with inhibition of retroelements involved in carcinogenesis and simultaneous stimulation of expression of retrotransposons that are not involved in the mechanisms of tumor development and have immunogenic properties. For this, microRNAs derived from transposons can be used as guides for DNA methyltransferases. An analysis of scientific literature revealed 41 such microRNAs of which decreased expression in kidney cancer was established for miR-95, -887, -652, -585, -511, -502, -495, -493, -487b, -335; increased for miR-1249, -1266, -151a, -211, -2114, -2355, -28, -3144, -340, -342, -374a, -374b, -3934, -421, -545, -576, -582, -584, -616, -769; and specific expression in different tumor subtypes for miR-708, -577, -450b, -326, -3200, -31, -224, -192, -1271. Since activation of retroelements can lead to insertions into new genome loci with formation of new mutations involved in carcinogenesis, a promising direction in integrated immunotherapy of kidney cancer is the use of reverse transcriptase inhibitors.

Prostate cancer is an extremely important problem in current urologic oncology. For a long time, the golden standard of treatment of common forms of prostate cancer at the stage of distant metastases was androgen deprivation therapy directed at suppression of native testosterone level. Combination treatment using long-term androgen deprivation therapy and new generation antiandrogens is currently a scientifically substantiated conceptually new standard of therapy which has replaced treatment paradigm using androgen deprivation therapy as a monotherapy in patients with metastatic hormone-sensitive prostate cancer. The article presents the results of large trials performed in patients with metastatic hormone-sensitive prostate cancer and characterizes the role of one of the most effective and safe drugs, darolutamide, used to treat patients of this subgroup.

Currently, genetically engineered drugs are widely used in oncological clinical practice which has significantly increased treatment cost. One of the most effective ways to decrease cost is substitution of an innovative drug after patent expiration with a reproduced compound – biosimilar.

In this article, a problem of biosimilars is actualized both worldwide and in Russia, characteristics of these products are described, and the path of the agents from the moment of reproduction through preclinical and clinical trials to introduction into real clinical practice is traced, examples of such trials are presented.

The results of clinical trials of effectiveness and safety of Pembroria® in patients with various oncological pathologies are described in detail. The first data from the multicenter prospective post-marketing trial PERFECTION are presented demonstrating similar effectiveness and tolerability results for the biosimilar in a multicohort patient category compared to pembrolizumab molecule.

Manufacturing of high-quality analogs and their introduction into clinical practice create a possibility to provide more patients in need with modern highly effective and safe drugs as well as increases effectiveness of the state healthcare system.