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Cancer Urology

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Vol 14, No 4 (2018)
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https://doi.org/10.17650/1726-9776-2018-14-4

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

16-21 2147
Abstract

Background. Clear cell renal cell carcinoma is the most frequent and most aggressive kidney cancer. Approximately 30 % at the initial diagnosis reveal distant metastases. This is due to the fact that kidney cancer in the early stages is asymptomatic. Very often (about 50 %), kidney cancer is detected by chance, during a routine examination or during treatment for other reasons. In this regard, the development of new methods of early diagnosis of clear cell renal cell carcinoma is actual.

Materials and methods. The levels of mRNA expression and methylation of a number of genes in the surgical material of paired samples (normal kidney tissue and tumor, 21 clinical cases) were studied. Quantitative determination of gene expression was performed using real-time polymerase chain reaction on a Step One Plus instrument (Applied Biosystems, USA) using TaqMan®Gene Expression Assays (Applied Biosystems, USA). High molecular DNA was isolated from tissue by phenol-chloroform extraction. Methyl-specific polymerase chain reaction was performed on a T100 Thermal Cycler amplifier (Bio-Rad, USA).

Results. As a result of joint analysis of the levels of gene expression and methylation, a system of potentially diagnostic markers has been developed, including the determination of the expression of a number of protein coding genes and the hypermethylation of several miRNA genes in tumor samples. Simultaneous determination of expression and methylation allows for the correct identification of tumors as SCRV with a sensitivity of 95.24 % (95 % confidence interval 76.18–99.88 %) and specificity of 95.24 % (95 % confidence interval 76.18–99.88 %).

Conclusion. According to the results of the study, a system was developed based on the determination of the expression levels of the CA9, HIG2, EGLN3,  NDUF4L2  genes and the methylation of the MIR9-1, MIR34b/c,  MIR124a-3,  MIR129-2.  Depending on the requirements for sensitivity, reliability of determination, or ease of implementation, various combinations of these genes are possible.

22-28 878
Abstract

The objective is to perform comparative analysis of intra- and postoperative complications of retroperitoneoscopic radical nephrectomy (RRN) and laparoscopic radical nephrectomy (LRN) for large tumors.

Materials and methods. The study includes examination and treatment data for 108 patients with stage T1—3a renal cell carcinoma.

Results and conclusion. A number of advantages of RRN compared to LRN were demonstrated associated with shorter surgery duration with fast processing of the renal pedicle, lower blood loss, lower use of analgesics in the postoperative period, shorter duration of hospitalization, and quick recovery after the surgery. The rate of intra- and postoperative complications for RRN was 19.2 and 17.3 %, for LRN — 33.9 and 37.5 %, respectively. Complications associated with abdominal organs were absent for RRN. After LRN, the rate of serious complications was significantly higher than after RRN.

30-36 941
Abstract

Objective: to assess safety of left renal vein (LRV) ligation during circular resection of the inferior vena cava in right-side kidney carcinoma with tumor venous thrombosis.

Materials and methods. We selected medical data of 63 renal cell carcinoma patients with tumor venous invasion undergone nephrectomy, thrombectomy, IVC resection with LRV ligation (Group 1; n = 29 (46.0 %)) or preservation of venous outflow from the contralateral kidney (Group 2; n = 34 (54.0 %)). Median age of study participants was 56.0 + 8.8 years (range: 32—72 years); a male to female ratio was 1:1.9. Such parameters as age, gender, median glomerular filtration rate (GFR), stages of chronic kidney disease (CKD), blood loss, and duration of surgery were comparable across the two groups (р >0.05 for all parameters). Median follow-up was 32.8 months (range: 1—226 months). Results. We observed no significant changes in median GFR in the late postoperative period compared to baseline among patients with ligated LRV (65.7 vs 71.2 mL/min/1.73 m2; р >0.05) and patients with preserved venous outflow from the contralateral kidney (60.6 vs 68.4 mL/min/1.73 m2; р>0.5). Patients that underwent LRV ligation were less likely to have reduced GFR compared to those with normal contralateral renal venous outflow (34.5 % vs 44.1 %; p >0.05). However, participants with ligated LRV had CKD upstaging (from stage 0—I to stage I—II) more frequently than participants with preserved venous outflow (27.6 % vs 5.9 %; р = 0.022). None of the patients developed stage III CKD after LRV ligation.

Conclusion. LRV ligation during circular resection of the IVC in right-side renal cell carcinoma patients with tumor venous thrombosis does not lead to a clinically significant decrease in long-term deterioration of renal function.

37-47 2063
Abstract

The current standard of treatment for patients with metastatic kidney cancer is targeted therapy, and the choice of a first-line drug is a difficult task for an oncologist in actual clinical practice. The article offers the data analysis, including information on 15 treated patients, and presents clinical efficacy of the targeted drug pazopanib as the first-line therapy in patients with metastatic kidney cancer with various sites of metastatic foci. The drug showed evidence of a convincing response to treatment, especially for metastatic foci in the lungs and adrenal glands.

48-52 1011
Abstract

This review of renal cell carcinoma describes new diagnostics and treatment standards, new guidelines from international professional organizations, key studies, and some articles of interest for oncological urologists published in 2018.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

53-67 1674
Abstract

Objective: to evaluate the prognostic value of pathogenic germline BRCA1, BRCA2 and CHEK2 mutations on biochemical relapse-free survival (BRFS) and metastasis-free survival (MFS) following radical treatment in patients with localized and locally advanced prostate cancer (PCa).

Materials and methods. Tumor features and outcomes of 102 patients with PCa were analyzed. In all patients nadir prostate-specific antigen (PSA) have been achieved: radical prostatectomy was undergone by 85 patients; 17 patients received radical radiotherapy. Exclusion criteria were postoperative nadir PSA >0.2 ng/mL, adjuvant hormone therapy. During follow-up a total of 65 (63.7 %) patients developed biochemical relapse (BCR), and 39 (38.2 %) patients developed metastatic progression of PCa. All patients were genotyped for clinically significant pathogenic germline mutations 1100delC, I157Tand IVS2+1G>A in the CHEK2gene, 185delAG, 4153delA, 5382insC, 3875del4, 3819del5, C61G, 2080delA in the BRCA1 gene, 6174delT in the BRCA2 gene by polymerase chain reaction real-time using a set “OncoGenetics” (LLC “Research and Production Company DNA-Technology”, Russia, registration certificate № 2010/08415). The second step was the determination of the coding part of the BRCA1 and BRCA2 genes by the Sanger sequencing using a set “Beckman Coulter enomeLab GeXP”.

Results. Pathogenic germline mutations in the CHEK2 gene were identified in 16 (15.7 %) patients: heterozygous missense mutation I157T (c.470T>C, rs17879961) was identified in 15 (14.7 %) patients, heterozygous mutation IVS2+1G>A (c.319+1G>A, rs765080766) was identified in 1 (0.9 %) patient. No cases of the 1100delC mutation in the CHEK2 gene and clinically significant mutations in the BRCA1 and BRCA2 genes were detected. Germline mutations I157TandIVS2+1G>A in the CHEK2gene are statistically significant independent unfavorable prognostic factor for BRFS (hazard ratio (HR) 3.272; 95 % confidence interval (CI) 1.688—6.341, p <0.001) and marginally significant independent unfavorable prognostic factor for MFS (HR 2.186; 95 % CI 0.932—5.126, p = 0.072). Subgroup analysis confirm independent prognostic value of germline CHEK2 mutations in patients with localized PCa (for BRFS HR 3.048; 95 % CI 1.024—9.078; p = 0.045; for MFS HR 5.168; 95 % CI 1.231—21.699; p = 0,025), and its marginally significant prognostic value in patient with locally advanced PCa T3-T4N0M0 (for BRFS HR 3.099; 95 % CI 0.991-9.689; р = 0.052) and TanyN1M0 stage (for MFS HR 5.089; 95 % CI 0.724-35.755; p = 0.102). Germline mutations I157T and IVS2+1G>A in the CHEK2 gene are associated with increased risk of early BCR during 12 months (HR 3.795; 95 % CI 2.06-6.98; p <0.001) and early metastatic progression during 24 months (HR 6.72; 95 % CI 2.02-22.34; p = 0.004) following radical treatment. This study has certain limitations due to its retrospective recruitment and a small sample of patients.

Conclusions. Our results confirm that germline CHEK2 mutations I157T and IVS2+1G>A are an unfavorable prognostic factor for patients with PCa, associated with increased risk of early biochemical relapse and metastatic progression, worse BRFS and MFS.

68-78 976
Abstract

Objective: to develop and substantiate the method of stabilization of urethrovesical anastomosis with retropubic prostatectomy to improve the results of early recovery of urinary retention.

Materials and methods. 58 patients who had undergone radical prostatectomy were enrolled into the prospective study. The patient population was divided into two groups by the blinded randomization. The first control group consists of 29 men who underwent traditional routine surgical treatment. The second main group (29 patients) who underwent novel surgical treatment with making urethrocysteoanastomosis based on original method (Patent for invention № 2559588 from 14 Jul 2015 “Method of propylaxis of urinary incontinence after retropubic prostatectomy”).

Results. At the moment of the hospital discharge the urine continence was achieved by the 20.7 % (n = 6) patients from the first group and 48.3 % (n = 14) patients from the second group. During the follow-up period in a month after surgery urine continence was maintained by the 37.9 % (n = 11) patients from the first group and 72.4 % (n = 23) patients from the second group, in three months after surgery — 62.0 % (n = 18) patients from the first group and 79.3 % (n = 23) patients from the second group. After the 6 months follow-up period 75.9 % (n = 22) patients from the first group and 86.2 % (n = 25) patients from the second group maintain urine continence. One-year follow-up period showed urine continence in 89.7 % (n = 26) patients from the first group and 93.1 % (n = 27) patients from the second group Conclusion. The surgical technique developed and introduced into clinical practice made it possible to stabilize urethrocysteoanastomosis, prevent or significantly shorten the incontinence period within the first year after retropubic prostatectomy, and improve the quality of life of patients.

79-86 903
Abstract

Background. Due to the development of visualization methods of examination in a heterogenous group of patients with prostate cancer recurrence, it has become possible to detect cases of oligometastatic disease.

The objective is to evaluate intermediate term surgical and oncological results of salvage lymph node dissection (sLND) in patients with oligometastatic recurrence of prostate cancer confirmed by positron emission tomography-computed tomography (PET-CT).

Materials and methods. The experience of treatment of 13 patients with recurrent prostate cancer who underwent sLND is presented. The characteristics of patients prior to sLND, surgical and oncological results were evaluated. A comparison of sLND results after PET-CT with choline and 68Ga-prostate specific membrane antigen (68Ga-PSMA) was performed.

Results. Median age was 65years (interquartile range (IQR) 59—70 years), median level of prostate-specific antigen was 2.8 ng/ml (IQR 1.3—4.6 ng/ml). Complications were observed in 4 of 13 patients (grade IIIа or lower per the Clavien—Dindo classification). Median follow-up duration was 46 months (IQR 11—50 months), response to sLND was observed in 6 patients and full response (prostate-specific antigen level <0.2 ng/ml) in 4. Median time to prescription of androgen deprivation therapy after sLND was 13.6 months (IQR 5.2—30.7 months). In 5 patients, for maximum follow-up period androgen deprivation therapy wasn’t performed. No statistically significant differences between patients who underwent sLND after PET-CT with choline and 68Ga-PSMA, were observed except for the follow-up period.

Conclusion. Therefore, sLND in carefully selected patients is a safe intervention allowing to delay or fully cancel androgen deprivation therapy in the presented follow-up period.

87-94 789
Abstract

Radium-223 is the 1st nuclide medicine from the group of alpha emitters, its use is associated with an increase in overall survival, a delay to bone complications and a significant improvement the quality of life, proven placebo-controlled randomized studies in patients with castration-resistant prostate cancer in the presence of bone metastases and no visceral ones. Perhaps the еarly use of radium-223 in combination with enzalutamide or abiraterone in castration-resistant prostate cancer patients with bone metastases, before the start of treatment with taxanes is reasonable.Today, the issue of embedding modern nuclide therapy in the accepted system of treating castration-resistant prostate cancer.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

95-102 1547
Abstract

Objective: to study the frequency of surgical complications and postoperative mortality after radical cystectomy (RCE).

Material and methods. In study included 107 patients who underwent RCE by one surgeon. Starting in 2015, the protocol for accelerated recovery of patients after surgery, ERAS was applied in all patients undergoing RCE. The frequency of complications and mortality was studied depending on the age of the patients and the ERAS protocol. There were 84 male (78.5 %) and 23female (21.5 %) in this study. All patients were divided into 2 groups: 1st group — 89 (83.0 %) people younger 75 years and 2nd group — 18 (17.0 %) people from 75 years and older. Depending on the application of the ERAS protocol, patients in each group were divided into 2 subgroups. Group 1st consists of subgroups: 1(A) — 40 (45.0 %) patients with ERAS protocol, 1(B) — 49 (55.0 %) patients without ERAS protocol. Group 2nd also consists of subgroups: 2(A) — 8 (44.4 %) patients with ERAS protocol, 2(B) — 10 (55.6 %) patients without ERAS protocol. The average age of the patients was 65.5 (32—85) years.

Results. Totally, over the 90-day period after the operation, 55 cases (51.4 %) of complications were recorded: Clavien—Dindo I—II in 1st group — 27 (30.3 %), in 2nd group — 8 (44.4 %). Complications of Clavien—Dindo III—IV in the 1st group — 15 (16.8 %), in the 2nd group — 5 (27.7 %). The overall 90-day mortality was 10 cases (9.3 %): in 1st group — 8 (9.0 %) patients, in 2ndgroup — 2 (11.1 %) patients. According to the comparative study of the use of the ERAS protocol in subgroup 1(A), the incidence of complications of the Clavien—Dindo I—II category was noted in 11 (27.5 %) patients, and in subgroup 1(B) in 16 (32.6 %) patients. Complications of Clavien—Dindo Ш—IV in subgroup 1(A) were observed in 5 (12.5 %) patients and in subgroup 1(B) — in 10 (20.4 %) patients; in subgroup 2(A), the incidence of Clavien—Dindo I—II complications was noted in 3 (37.5 %) patients, and in subgroup 2(B) — in 5 (50.0 %) patients. Complications of Clavien— Dindo III—IV in subgroup 2(A) were observed in 2 (25.0 %) patients and in subgroup 2(B) — in 3 (30.0 %) patients. Thus, the ERAS protocol decreased the number of complications in the subgroup 1(A) compared to the subgroup 1(B) (z = 1.44; p = 0.08) and between the subgroup 2(A) and 2(B) (z = 1.39; p = 0.09). Also there was an increase in the number of complications in older subgroups: in subgroup 2(B) compared with subgroup 1(B) (z = 1.86; p = 0.068).

The 90-day mortality in subgroup 1(A) was in 3 (7.5 %) cases, 1(B) — 5 (10.2 %) cases. The 90-day mortality in subgroups 2(A) was in 1 (12.5 %) case, in subgroup 2(B) was 1 (10.0 %) cases. Repeated hospitalization for the first 90 days was 14 (13.0 %) cases, with differences in the frequency of rehospitalization depending on age and application of the ERAS protocol.

Conclusion. RCE is an acceptable method of treatment in patients of the older age group and should be performed in hospitals with experience of regular treatment of this nosology. Application of the ERAS protocol (accelerated recovery after surgery) in patients undergoing RCE allows, regardless of age, to reduce the incidence of early postoperative surgical complications and mortality.

103-109 1933
Abstract

Worldwide, bladder cancer is the 7th most common cancer type in men and 11th in both sexes. The standardized by age incidence is 9.0 cases per 100.000 people among men and 2.2 cases per 100.000 people among women.

The most common (>90 %) histological form of malignant epithelial tumors of the bladder is transitional cell carcinoma. Transitional cell carcinoma with squamous cell, glandular, or trophoblastic differentiation is rare. Squamous cell carcinoma comprises about 5 % of malignant epithelial bladder tumors, adenocarcinomas from 0.5 to 2.0 %. Small-cell and spindle-cell carcinomas are exceptionally rare (<0.5 %). Primary small-cell, or neuroendocrine, carcinoma is a very rare disease with incidence of <0.5 % of all bladder tumors. Presumably, small-cell carcinoma of the bladder (SCCB) is similar to small-cell carcinoma of the lung and consists of a population of a relatively homogenous cells with scant cytoplasm and hyperchromatic nuclei; extensive necrosis is also common. Histogenesis of SCCB is unknown, but there are 2 hypotheses on development of cancerous cells: from rare neuroendocrine cells and multipotent stem cells of the bladder.

Prognosis is poor for most patients: in the report by I. Trias et al., median survival was less than 1 year, long-term survival for 5 or more years was extremely rare. In more than a half of patients, metastatic lesions of the regional lymph nodes, liver, or bones were observed during diagnosis.

In the Russian literature, the problem of SCCB remains insufficiently investigated due to low incidence of this morphological type. Treatment is mostly administered empirically.

110-117 788
Abstract

The paper reviews the basic avenues of research and the recent developments in clinical research. Bladder cancer remains a mystery disease, it puts oncologists and urologists a lot of questions that hard to answer. According to epidemiological data of 2017 bladder cancer incidence increased in Russia, and bladder cancer of the late stages was diagnosed in the large amount of patients in 2017: in 12.9 % of all patients with newly detected bladder cancer clinical stage III was diagnosed, and in 9.9 % of patients the cancer of the stage IV was diagnosed. The mortality among patients with newly diagnosed bladder cancer was 14.9 % in the 1st year after the disease diagnosis. Cancer research carried out in the last decades focused on the tumor biology, tumor pathogenesis and the development of new diagnostic and treatment methods. Clinical treatment results and biological characteristics of the tumor were compared and some practical conclusions were made. Comparative effectiveness of surgery, radiation therapy and drug therapy for cancer treatment was analyzed. Special attention was paid to the rate of complications developed immediately after the radical cystectomy and in 30 and 90 days after the surgery. This is the problem of great importance because the presence of complications has impact on the cost of the treatment. Clinical studies of PD-1/PD-L1 inhibitors effectiveness in patients with advanced urothelal cancer were described in the paper.

REVIEW

124-138 1056
Abstract

Bladder cancer (BC) is represented by non-muscle-invasive forms at the stage Ta, T1, CIS (NMBC) in 75 % of cases. The gold standard of treatment of NMBC patients is transurethral resection, but its implementation does not always allow the patient to be relieved of the recurrence of the disease. In this regard, patients with a low risk of progression after transurethral resection are administered by intravesical chemotherapy, with high risk (T1G2/3) – using instillation with BCG (Bacillus Calmette–Guerin) vaccine. Searching of NMBC markers for laboratory diagnostics, which would help to determine sensitivity or resistance to the planned type of adjuvant therapy remains an actual problem. The data published mainly in the last 5–7 years about genetic predictors of the response to adjuvant chemotherapy and, to a greater extent, immunotherapy with BCG vaccine, are reviewed in this work. Allele combinations in the genes involved in immune response, xenobiotic biotransformation and other loci that are associated with the response to the adjuvant NMBC therapy in meta-analyzes are systematized. Also, expression profiles of mRNA, microRNA and proteins, as well as panels of methylated loci associated with the effectiveness of chemotherapy and immunotherapy of NMBC are considered. It was demonstrated that the somatic mutations sequencing in the primary tumor and the total mutational load using high-throughput sequencing technologies (NGS) identified a number of potential prognostic markers. Perhaps, the mutational load will be more widely used as a highly informative predictor of immunotherapeutic effect in BC: BCG therapy of NMBC and BC targeted therapy using the inhibitors of immune control points, after the standardization of the analysis. This review is intended to oncologists, geneticists, molecular biologists, urologists, pathologists and other specialists working in the field of molecular genetics in oncological urology.

139-149 3421
Abstract

The treatment landscape for metastatic hormone-sensitive prostate cancer (mHSPC) has rapidly evolved over the past 5 years. Although androgen-deprivation therapy is still the backbone of treatment, the addition of docetaxel or abiraterone acetate has improved outcomes for patients with mHSPC and become standard of care. With multiple treatment options available for patients with mHSPC, treatment selection to optimize patient outcomes has become increasingly difficult. Here, we review the clinical trials involving androgen-deprivation therapy plus docetaxel or abiraterone and provide clinicians with guidelines for treatment. Although surgery and/or radiation are standard of care for localized, intermediate- and high-risk prostate cancer, these treatments are not routinely used as part of initial treatment plans for patients with de novo mHSPC. Recent clinical data are challenging that dogma, and we review the literature on the addition of surgery and radiation to systemic therapy for mHSPC.

CLINICAL CASE

150-154 952
Abstract

Primary tumors of the seminal vesicles (SVs) are uncommon in the routine practice of urologists. Their diagnosis is complicated by an absence of early signs of the disease. Therefore, usually SVs tumors are detected accidentally during instrumental examinations. Primary tumors of the SVs can be benign. In the Medline, PubMed, and Google Scholar databases we have found 25 descriptions of clinical cases of cystadenomas of the SVs, while in Russian medical literature no publications on the topic can be found. The main diagnostic methods are contrast-enhanced computed tomography, magnetic resonance imaging, and fine needle biopsy. Surgery scale varies from SV resection and vesiculec¬tomy to vesicle resection with prostatectomy and orthotopic neobladder reconstruction and lower anterior resection of the rectum. Considering that primary SV tumors are a rare pathology, there’s no consensus on the scale of surgical intervention.

In view of the rarity of the disease and lack of its descriptions in Russian medical literature, we find it interesting to demonstrate a clinical observation of a patient with cystadenoma of the left SV.

UROLOGICAL COMPLICATIONS IN CANCER PATIENTS

118-123 836
Abstract

Background. Radiation therapy for patients with cervical and endometrial cancer is often associated with the development of radiation cystitis which is treated mainly symptomatically.

Objective was the rationale for dendritic cell vaccines in the treatment of the bladder damage after radiation therapy.

Materials and methods. The treatment effectiveness of late radiation damage to the bladder in 26 oncogynecologic patients after chemoradiotherapy was analyzed in the article.

Results. The effectiveness of 25.000.000 autologous dendritic cells vaccine introduced into all the tops of the rhombus of Michaelis for 5 cycles with 2-week intervals was proved. Mucosal erosions, ulcerous defects and telangiectasia during dendritic cell therapy were managed in 100, 81.8 and 78.6 % of cases, respectively, while in control — in 66.7, 50 and 30 % of cases, respectively (p <0.05). One of the mechanisms of action of dendritic cell vaccines in the treatment of radiation injuries may comprise a high phenotypic plasticity of dendritic cells and macrophages and their ability to regulate inflammatory and anti-inflammatory functions and regenerate and repair damaged tissues.

Conclusion. The results of treatment for radiation cystitis resistant to the standard anti-inflammatory therapies demonstrate the obvious benefits of immunotherapy.



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ISSN 1726-9776 (Print)
ISSN 1996-1812 (Online)
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