Vol 14, No 3 (2018)
- Year: 2018
- Published: 30.09.2018
- Articles: 18
- URL: https://oncourology.abvpress.ru/oncur/issue/view/53
Full Issue
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
PROGNOSTIC VALUE OF MATRIX METALLOPROTEINASE 9 IN RENAL CELL CARCINOMA
Abstract
Objective: to assess matrix metalloproteinase 9 (MMP-9) expression in renal cell carcinoma cells and cells of intratumoral inflammatory infiltrates depending on clinical and morphological characteristics and postoperative survival.
Materials and methods. We evaluated MMP-expression in 108 renal cancer tissue specimens. The intensity of immunohistochemical staining was estimated by measuring integral optical density in cytoplasm.
Results. We found that the integral optical density of MMP-9 immunostaining in tumor cells and cells of intratumoral inflammatory infiltrates correlates with important prognostic factors for renal cancer, including histological type of cancer, TNM stage, tumor size, Fuhrman nuclear grade, metastasis, and 5-year postoperative survival.
Conclusion. Integral optical density of MMP-9 immunostaining is an additional prognostic factor for renal cell carcinoma.
17-24
CURRENTLY AVAILABLE TREATMENT OPTIONS FOR METASTATIC RENAL CELL CARCINOMA
Abstract
Over the last 10 years, the capacities of second-line systemic therapy for metastatic renal cell carcinoma (mRCC) changed significantly. Targeted therapy is a standard treatment for patients with mRCC. However, the choice of therapeutic agents for such patients remains challenging. In the absence of reliable prognostic biomarkers, physicians can use only the results of randomized clinical trials and their own routine experience with targeted drugs when choosing a regimen of second-line therapy. The article discusses the current situation with second-line therapy with the three new options available for patients with mRCC. It also contains a case report, describing our successful experience of treatment a female patient that received 6 variants of chemotherapy with good effect during 89 months after the diagnosis.
25-36
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER
HYPOXIA-DEPENDANT MECHANISMS OF REGULATING NEOANGIOGENESIS AND APOPTOSIS IN PATIENTS WITH EARLY RECURRENT LOCALIZED PROSTATE CANCER
Abstract
Objective. Examination of the expression of genes responsible for hypoxia-dependent control of transcription, neoangiogenesis, and apoptosis in tumor tissue of the prostate, in patients with localized prostate cancer (РС) with biochemical recurrence (BR) and without recurrences after radical prostatectomy (RPE).
Materials and methods. The main group included 56 patients with localized PC who had been diagnosed with BR within two years after RP. 60 patients with localized PC who did not relapse had a comparative group. 55 patients in whom operative biopsy specimens of the prostate gland were taken within healthy tissues with the removal of benign prostatic hyperplasia were combined into a control group. Determination of the expression level of the BAX, BCL2, VEGFA and HIF1α genes in tumor tissue was performed by real-time polymerase chain reaction.
Results. In patients with localized PC after RPE, development of BR is associated with an increase in the expression of BCL2, VEGFA and HIF1α genes and a decrease in the expression of the BAX gene. In patients with localized PC and early recurrence of tumor tissue through a hypoxia-dependent factor that enhances transcritical processes in tumor cells, neoangiogenesis is activated, which is associated with inhibition of apoptosis of tumor cells by enhancing the expression of the antiapoptotic gene BCL2.
Conclusion. Determination of the expression of BAX, BCL2, VEGFA and HIF1α genes in tumor tissue with localized PC allows further assessment of the risk of disease progression after surgical treatment.
37-42
POSTOPERATIVE COMPLICATIONS OF MINIMALLY INVASIVE THERAPIES FOR PROSTATE CANCER
Abstract
Prostate cancer is the most common cancer among men. Radical prostatectomy (open, laparoscopic, or robotic) remains the main method of surgical treatment for prostate cancer. However, minimally invasive therapies for prostate cancer are becoming increasingly popular in recent years, because they have similar efficacy as open surgery. The most studied minimally invasive therapies are cryoablation, high intensity focused ultrasound (HIFU), and brachytherapy.
Despite the minimization of damage to neighboring structures, minimally invasive procedures can cause a number of complications, like any other surgical interventions. Each method has specific limitations and the most typical complications. Since multiple minimally invasive methods are currently available, we can ensure an individual approach to each particular patient, thus using the advantages of the methods and avoiding possible complications. This article covers the most frequent and severe complications of minimally invasive therapies for prostate cancer, as well as the methods of their prevention and treatment.
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ROBOT-ASSISTED PELVIC LYMPH NODE DISSECTION USING ICG TESTING IN PATIENTS WITH PROSTATE CANCER
Abstract
The objective is to investigate the possibility of using fluorescent testing in robot-assisted radical prostatectomy using indocyanine green (ICG testing) during pelvic lymph node dissection (PLND) in patients with localized prostate cancer.
Materials and methods. Fifteen minutes prior to robot-assisted PLND, intraprostatic transperineal administration of 0.4 ml of indocyanine green (ICG) per lobe under transrectal ultrasound control was performed. Fluorescence map was used. After activation of the FireFly mode, fluorescence of the lymph nodes was evaluated. If a sentinel lymph node was present, lymph node dissection was performed using the FireFly mode. If fluorescence was diffuse, PLND using this option wasn’t performed.
Results. In total, 35 patients with localized prostate cancer underwent surgery. Mean age was 62.0 ± 6.5 years (41–68 years), mean prostatespecific antigen level prior to surgery was 15.6 ± 11.3 ng/ml (1.5–27.0 ng/ml). Postoperative examination revealed micrometastases in the lymph nodes in 7 (20 %) cases. Sentinel lymph nodes were detected in 29 patients. Intraoperative examination revealed sentinel lymph nodes metastases in 6 (17 %) cases, in other cases (83 %) metastases were absent. Morphological examination showed that in 5 (83 %) of 6 patients with lesions in the sentinel lymph node, micrometastases in other lymph nodes were present. In patients without lesions in the sentinel lymph node, no micrometastases in other lymph nodes were observed. PLND complications included lymphocele in 3 (8 %) patients, prolonged drain indwelling time in 5 (14 %) patients.
Conclusion. Initial experience of our clinic shows reproducibility and low complications profile of fluorescence monitoring in the near-infrared region using ICG testing during robot-assisted PNLD. In conditions of continuous increase in the number of performed robot-assisted radical prostatectomies, ICG testing is a promising minimally invasive method for evaluation of regional metastases allowing to detect the sentinel lymph node. This approach allows to decrease the number of complications associated with PLND.
51-57
NEOADJUVANT AND ADJUVANT CHEMOHORMONAL THERAPY IN PATIENTS WITH HIGH-RISK AND VERY HIGH-RISK PROSTATE CANCER: OUR EXPERIENCE
Abstract
Background. The approach to the management of prostate cancer with lymph node metastases has recently moved towards aggressive multimodal treatment with the use of the most rational combinations that are currently available.
Objective: to assess the efficacy and tolerability of chemohormonal therapy (CHT) in patients with high-risk and very high-risk prostate cancer.
Materials and methods. An open prospective clinical trial evaluating the efficacy and tolerability of neoadjuvant and adjuvant CHT in patients with high-risk and very high-risk prostate cancer was initiated in 2016 at the P.A. Herzen Moscow Oncology Research Institute. Patient recruitment is still ongoing.
A total of 64 patients with high-risk and very high-risk prostate cancer (сT3N0–T3N+М0, prostate specific antigen (PSA) ≥20 ng/mL, and Gleason score of 8–10) were recruited since July 2016. All patients were examined prior to treatment initiation and after 3 and 6 courses of therapy. The examination included pelvic magnetic resonance imaging, ultrasound imaging of the abdominal cavity and retroperitoneal space, transrectal ultrasound imaging, and chest radiography or computed tomography. Serum PSA level was evaluated before each course of therapy. Bone scintigraphy was performed before treatment and after its completion. Study participants were divided into two groups. Group A included patients that initially underwent surgical treatment and then 6 courses of CHT no later than 6 weeks after surgery: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. Patients also received hormonal therapy with luteinizing hormone-releasing hormone analogue (aLHRH) given in depot injections every 28 days.
Group B included patients that initially received 6 courses of CHT: docetaxel 75 mg/m2 given intravenously on day 1 of a 21-day cycle and oral prednisolone 10 mg/day. After that, patients underwent radical prostatectomy with pelvic lymphadenectomy no later than 4 weeks after the completion of chemotherapy. Patients also received hormonal therapy with aLHRH given in depot injections every 28 days. The total treatment duration was 6 months.
Results. The group of adjuvant CHT included 24 patients with high-risk prostate cancer (T3b–4N+М0 with at least 5 regional lymph node metastases detected by morphological examination of surgical specimens). All patients had Gleason score 8–10 tumors. Mean age of patients was 63.0 ± 7.7 years (range: 46–72 years). In total, all patients received 142 courses of CHT. By the time of publishing this article, 23 (96 %) of patients completed their treatment.
The group of neoadjuvant CHT included 40 patients with very high-risk prostate cancer (T3b–4N+М0 with metastases to pelvic and retroperitoneal lymph nodes detected by instrumental examination). All patients had Gleason score 8–10 tumors. Mean age of patients was 61.0± 6.4 years (range: 43–69 years). In total, all patients received 236 courses of CHT. By the time of publishing this article, 36 (90 %) of patients completed their treatment. Thirty-five patients (87 %) underwent radical prostatectomy with extensive pelvic and paraaortic lymphadenectomy. Routine pathological examination demonstrated that all patients had signs of tumor destruction. Thirty-three participants (94 %) had grade II therapeutic pathomorphosis, whereas 2 patients (6 %) had grade III therapeutic pathomorphosis.
Median PSA relapse-free survival (PSA-RFS) rate in the neoadjuvant CHT group was 10 months. Serum PSA of 0.1 ng/mL 1 month postoperatively correlated with longer RFS (р = 0.04). Biochemical relapse (PSA level >0.2 ng/mL) was observed in 6 patients (15 %) from this group. Later these patients received hormonal therapy with aLHRH. Median PSA-RFS in the adjuvant CHT group was 11 months.
The main adverse events in the two groups were hematological toxicity, observed in 24 patients (34.29 %), and gastrointestinal toxicity, observed in 9 patients (12.86 %) (diarrhea (n = 6) and stomatitis (n = 3)). Only grade I–II toxicity was registered so far. Two patients (3.1 %) had febrile neutropenia, which required cytostatic dose reduction by 20 %. Relatively good tolerability and acceptable quality of life allowed the vast majority of patients to be treated on an outpatient basis.
Conclusion. So far, we can make only a preliminary conclusion that adjuvant and neoadjuvant CHT is a promising treatment strategy for high-risk and very high-risk prostate cancer.
58-67
NEW TREATMENT STANDARD FOR PATIENTS WITH NON-METASTATIC CASTRATION-RESISTANT PROSTATE CANCER
Abstract
Men with nonmetastatic, castration-resistant prostate cancer and a rapidly rising prostate-specific antigen level are at high risk for metastasis. Until recently there was no standard of treatment for this category of patients. A total of 1401 patients with nonmetastatic, castration-resistant prostate cancer and a prostate-specific antigen doubling time of 10 months or less underwent randomization to double-blind, phase III PROSPER trial. Patients were continuing androgen-deprivation therapy in combination with enzalutamide (at a dose of 160 mg) or placebo once daily. The median metastasis-free survival was 36.6 months in the enzalutamide group versus 14.7 months in the placebo group. Enzalutamide treatment resulted in a 71 % lower risk of radiographic progression or death than did placebo (hazard ratio 0.29; 95 % confidence interval 0.24 to 0.35; p <0.001). Adverse events were consistent with the established safety profile of enzalutamide.
68-77
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
LASER EN-BLOC RESECTION OF NON-MUSCLE-INVASIVE BLADDER CANCER: CLINICAL AND MORPHOLOGICAL SPECIFICITIES
Abstract
Objectives to enhance the morphological diagnostic complex in order to predict postoperative outcomes in a more accurate way and to optimize patients with non-muscular invasive bladder cancer treatment.
Materials and methods. The study included 34 patients from 25 to 71 years old underwent laser en-block resection, the most of them were males – 28. In 9 cases multiple carcinomas (2 or more) were found. Huge tumors (2 cm or more in one dimension) were resected in 6 patients. Results. The major part of tumors removed (n = 22) histologically appeared to be papillary urothelial carcinomas with low grade of malignancy and PUNLMP; in 6 cases G2 was verified, one tumor with high malignancy potention – G3. In 3 patients intramuscular invasion was found (invasive carcinoma T2) excluding them from the study.
Discussion. Laser en-block resection of non-muscle-invasive bladder cancer appears to be the most optimal approach in operative treatment that provides representative histological material. For correct morphological estimate we recommend either to expand the resection zone to 1 cm which allows to remove circular resection margin or to take extra pinch biopsy from tumor crater (vertical margin). In 3 patients from our study positive circular margin was revealed histologically whereas foci of perineural and perivascular invasion were found in one case. A new subgrading of stage T1 depending on intramuscular invasion depth was suggested whereas the main criteria is the muscularis mucosae involvement.
Conclusion. Morphological estimate of circular resection margin provides an ability to predict postoperative outcomes and correct the treatment in one or another way. Subgrading for T1-stage tumors is recommended for following correct postoperative prognosis and possibility of tumor recurrence.
78-84
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. TESTICULAR CANCER
GENETIC ASPECTS OF TESTICULAR DYSGENESIS SYNDROME AND ASSOCIATED CONDITIONS
Abstract
Today it is noted that the most cases of the hypospadias, cryptorchidism, testicular microlithiasis, as well as problems of semen quality and testicular germ cell tumours can be a clinical manifestation of testicular dysgenesis syndrome caused by abnormal development of reproductive organs. In the last decade, technological progress in the molecular genetics has made possible to carry out a directed search for genetic factors associated with reproductive disorders in men. In the review we attempted to analyze available literature data on the testicular dysgenesis syndrome and its constituent condition and also to consider the risk factors associated with its development. We give particular attention to the consideration of genetic factors that determine the manifestation of testicular microlithiasis, cryptorchidism and testicular germ cell tumors, both individual clinical conditions and in the syndrome of testicular dysgenesis. Knowledge of the genetic aspects of reproductive damage will allow us to characterize the complex interconnection of the human genome with the clinical phenotype, clarify the role of unfavorable factors of the environment and the lifestyle of the individual, and suggest new approaches to treatment.
92-106
85-91
REVIEW
MOLECULAR EPIDEMIOLOGY OF RENAL CANCER
Abstract
Kidney cancer consists of renal cell cancer (RCC) accounting for over 90 % of all kidney carcinomas and the transitional cell cancer. Clear cell cancer is a predominant type (80–85 %) of RCC. Smoking, overweight, obesity, hypertension, occupational exposures to pesticides, specifically to trichloroethylene are considered causal risk factors for sporadic i.e. non-hereditary RCC. The majority of sporadic RCC have polygenic etiology. They develop as a result of combined effect of large number of low penetrance genetic susceptibility genes (genetic polymorphism). The interplay of exposures to environmental risk factors and genetic susceptibility of exposed individuals is believed to influence the risk of developing sporadic RCC. Inheritance of high penetrance genes is associated with very high risk of the RCC. To these genes belongs, for example, VHL (von Hippel–Lindau). Germline mutations in VHL are causing VHL syndrome and hereditary type of RCC. Risk of RCC in individuals with germ-line mutations is very high however the proportion RCC associated with these events is very low (>5–7 %). Environmental factors virtually do not influence the risk of these cancers.
The studies in molecular epidemiology based on candidate gene approach have shown that certain types (variants) of polymorphisms of GST, MTHFR, TYMS, VHL genes are associated with RCC. The genome wide association studies identified over twenty locus with single nucleotide polymorphism affecting the risk of RCC. The risk loci so far identified for RCC account for only about 10 % of the familial risk of RCC. Thus more studies with larger sample size are needed. As more RCC susceptibility alleles are discovered, deciphering the biological basis of risk variants should provide new insights into the biology of RCC that may lead to new approaches to prevention, early detection and therapeutic intervention.
107-119
SEQUENTIAL THERAPY OF METASTATIC CASTRATION-RESISTANT PROSTATE CANCER: NEW POSSIBILITIES
Abstract
Currently, doctors have at their disposal a number of drugs prolonging life of patients with castration-resistant prostate cancer (CRPC). The majority is approved for use as the 1st line therapy and, in absence of direct comparison, is considered potentially equally effective. Patients with CRPC need continuous treatment for suppression of disease progression resulting in sequential use of therapeutic agents. Modern standards and recommendations do not provide a clear algorithm for prescription, therefore an individual approach is necessary taking in account various factors of a particular case ranging from previous therapies to patients’ preferences. This article considers the most significant factors affecting CRPC therapy selection and ways of therapy optimization in compliance with the established treatment standards and taking into account the list of drugs approved for use in Russia.
120-127
ANNIVERSARIES
149-151
CLINICAL CASE
METASTASIS OF RENAL CANCER TO BREAST: DESCRIPTION OF CLINICAL CASE
Abstract
The main method of treatment of local stages of clear cell renal cancer is surgical. The question of conducting adjuvant irradiation and chemotherapy after radical operations is open. Patients with solitary distant metastases and a favorable prognosis may become candidates for surgical treatment. Surgical removal of isolated solitary metastases allows to achieve 35–60 % of 5-year overall survival. The patient, observed in N.N. Blokhin National Medical Research Center of Oncology with metastasis of renal cancer in the pancreas, and then in the breast is an extremely rare clinical case presented in this article.
128-132
133
18F-PSMA-1007 POSITRON EMISSION TOMOGRAPHY/COMPUTED TOMOGRAPHY IN THE DIAGNOSIS OF RECURRENT PROSTATE CANCER: CLINICAL OBSERVATION
Abstract
Objective: demonstration of possibilities of 18F-prostate specific membrane antigen-1007 (18F-PSMA-1007) positron emission tomography/computed tomography (PET/CT) for diagnostic prostate cancer recurrence.
The article presents clinical observation of the patient with prostate cancer biochemical recurrence after the multiple treatment. 18F-PSMA-1007 PET/CT demonstrates high sensitivity in prostate cancer recurrence diagnostic, in particular with low prostatic specific antigen level.
134-138
LARGE PAPILLARY UROTHELIAL NEOPLASM OF LOW MALIGNANT POTENTIAL: A CASE REPORT
Abstract
Last World Health Organization 2016/ISUP (International Society of Urologic Pathologists) papillary urinary tumor classification include papillary urothelial neoplasm of low malignant potential (PUNLMP). This type of tumor is characterized by minimal atypia as well as low recurrence and progression rates. The article describes a clinical case of large PUNLMP treatment.
139-142
CONGRESSES AND CONFERENCES
REVIEW OF THE ONCOLOGICAL UROLOGY PROCEEDINGS OF THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY (ASCO) 2018 ANNUAL MEETING
Abstract
The 54th American Society of Clinical Oncology (ASCO) Annual Meeting took place between 1st and 5th June in Chicago (USA) united more than 40,700 professionals of various fields. Oncological urology topics account for a considerable proportion of the Annual Meeting proceedings. In this article, a review of the most significant reports on cancer urology from the ASCO 2018 Annual Meeting is presented.
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