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Cancer Urology

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Vol 16, No 3 (2020)
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TO THE REVIEWERS: LETTER OF APPRECIATION

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

21-28 1259
Abstract

Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.

Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).
Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p <0.0001). In RCC patients the higher uKIM-1 level was observed at more advanced clinical disease stages: the values increasedfrom 2.0 ± 0.2 ng/ml at the stage I and 3.0 ± 0.5 ng/ml at the stage II—III to 4.4 ± 1.2 ng/ml at the stage IV. In the group of patients with stage IRCC, most representative by the number of cases (n = 44) the uKIM-1 levels correlated with the tumor size and were increased in patients with different histological subtypes of the tumor, including clear cell, papillary and chromophobe RCC. After nephrectomy, a monotonous decrease in uKIM-1 level was observed, and after 6 days its values approached the mean value in the control group. Two days after kidney resection, uKIM-1 increased and then decreased, remaining elevated after 6 days.
Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.

29-37 1395
Abstract

The treatment strategy for metastatic renal cell carcinoma (mRCC) has evolved with the emergence of anti-angiogenic drugs, in particular tyrosine kinase inhibitors (TKIs) targeting the vascular endothelial growth factor receptor (VEGFR) and immune checkpoint inhibitors (ICIs). Both treatment options improved patient outcomes and altered the natural history of mRCC. Clinical studies have focused on evaluating combination regimens containing ICI and VEGFR-targeted TKIs. The combination of axitinib with pembrolizumab (KEYNOTE-426) showed better results compared to sunitinib in patients with mRCC who had not previously received systemic therapy. In this article, we discuss the rationale for the combination of ICI and TKI based on preclinical data, as well as the clinical results obtained with the combination of axitinib with pembrolizumab in first-line patients in clinical trials.

38-52 2752
Abstract

The use of immunotherapeutic drugs as monotherapy and in various combinations for metastatic renal cell carcinoma has revolutionized the treatment of this disease. Thanks to the breakthrough studies carried out, the standard in the first line of therapy for metastatic renal cell carcinoma is now a combination of checkpoint inhibitors, as well as an immuno-oncological agent with a tyrosine kinase inhibitor.
This article presents updated data from the CheckMate 214 study with a minimum follow-up of 42 months. A review of studies on the efficacy of nivolumab in patients with renal cell carcinoma in the first line of therapy with the possibility of adding ipilimumab in case of progression of the disease on the background of monotherapy is carried out, as well as data on the use of a combination of nivolumab and ipilimumab in the second line of treatment.
Monotherapy with nivolumab has a certain effectiveness in a specific category of patients, for example, with potential intolerance to ipilim-umab or first-line tyrosine kinase inhibitors, as well as in patients with a favorable prognosis.
The combination of drugs nivolumab + ipilimumab is a highly effective treatment option in the first line of therapy with the potential for a sustained response in patients with RCC with an poor and intermediate risk, and in the second and subsequent lines requires further study.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

62-69 915
Abstract

Background. Targeted biopsy is proposed as a method of choice in the algorithm of prostate cancer diagnosis, but not all the features of method has been evaluated.
Objective: determine the rational number of targeted biopsy samples in patients with clinically significant prostate cancer.
Materials and methods. The magnetic resonance imaging and fusion biopsy data of 156 patients with suspected prostate cancer were retrospectively evaluated.
Results and conclusion. In the study statistically significant dependence of the positive histological results in patients with clinically significant prostate cancer from the number of biopsy samples was found. The potential probability of a false negative histological examination with an insufficient number of biopsy samples was noted. These results confirm the latest published data of potential targeted biopsy false in true positive patients after multiparametric magnetic resonance imaging. An increase in the number of biopsy samples in the target lesion reduces the likelihood of false-negative results. The main causes of such discrepancy are some technical laxity and the heterogeneous histological structure of prostate cancer. Increase the number of biopsy cores can reduce the likelihood of false-negative results.

 

70-79 816
Abstract

Objective: to determine the degree of heterogeneity of prostate cancer Gleason 6 (3 + 3) by assessing: long-term oncological results, mismatch of pre- and postoperative degree of prostate cancer aggressiveness, preoperative clinical component.
Materials and methods. 528 patients with clinically localized prostate cancer and Gleason»s preoperative score of 6 (3 + 3). All patients were divided into 3 groups: group 1 (n = 151) — Gleason 6, prostate specific antigen (PSA) density <0.15ng/ml/cm3, ≤4 positive biopsy cores, <50 % lesion of the biopsy cores, group 2 (n = 229) — Gleason 6, PSA <10 ng/ml and group 3 (n = 148) — Gleason 6, PSA >10 ng/ml.
Results. Statistically significant differences between group 1 and group 2 were observed only when assessing PSA velocity (p <0.017). The median time to the development of biochemical relapse (BCR) in the study population was 12 (3—77) months. BCR in group 1 was observed in 1.98 % of patients, in group 2 and 3 — 7.86 and 14.19 %, respectively. Statistically significant differences in the time of onset of BCR within 2 years after surgery were found between groups 1 and 2 (p = 0.002) and group 1 and 3 (p = 0.0001). An increase in the degree of malignancy after surgery in group 1 was determined only in 13 % of patients, in group 2 in 27 %, in group 3 in 43 % of patients. The contribution of a greater postoperative degree of malignancy of prostate cancer to the development of BCR in group 1 was 1.32 % (2 out of 3 patients). Thus, in group 1 in the case of true Gleason 6 (3 + 3), the probability of BCR was 0.66 %.
Conclusion. PSA velocity before surgery showed a statistical difference between groups 1 and 2. Based on long-term oncological results after surgery, heterogeneous behavior of the tumor is observed among the study groups. Group 1 in comparison with group 2 and 3 showed the lowest frequency of increase in the Gleason score and the likelihood of developing BCR after surgery. These results may be useful in planning an individual patient treatment plan.

80-89 1191
Abstract

Background. The role of pathological response, which develops as a result of systemic therapy for localized and locally advanced high risk prostate cancer, is not still fully understood. There are no clear indications for neoadjuvant therapy and no data on the relationship between neoadjuvant therapy and median of overall or progression free survival. According to increasing interest for neoadjuvant chemohormonal therapy followed by radical prostatectomy, we evaluated the features of pathological response and its effects on overall and progression free survival rates.
Objective. Estimating residual disease and pathologic response to neoadjuvant therapy of high risk prostate cancer and its relationship with oncological results.
Materials and methods. This was a prospective randomized study: patients with prostate cancer of high and very high-risk groups (prostate specific antigen levels >20 ng/ml and/or Gleason score ≥8 and/or clinical stage ≥T2c) were treated with neoadjuvant chemohormonal therapy followed by radical prostatectomy (n = 36). The neoadjuvant course included the intravenous administration of docetaxel once every 21 days (75 mg/m2 up to 6 cycles) and the antagonist of the gonadotropin releasing hormone degarelix according to the standard scheme (6subcutaneous injections every 28 days). The prostate tissue was evaluated for the residual disease, features of pathological response according to the ABC system. Additionally, the expression of IHC markers (p53, bcl-2, p16, Ki-67, androgen receptors, c-MYC, ERG, PTEN) was evaluated on postoperative material using tissue microarray.
Results. A totally of 480 H&Epostoperative and 775 H&E biopsy slides were analyzed. Group A included 10 (32.3 %) cases, group B — 16 (51.6 %), and group C — 5 (16.1 %). The variance analysis revealed a significant difference in the frequency of more localized forms of prostate cancer in group B (43.7 %) (p = 0.028). During assessment we did not found any relationship ABC system assignment and preoperative prostate specific antigen level, the presence of a positive surgical margin, the pathological stage of diseases or regional lymph nodes involvement. However, the values of relapse-free survival vary sharply between groups: the highest median of relapse-free survival was found in group B — 23.02 ± 12.61 months, patients of groups A/C could not achieve the level of median relapse-free survival — 11.7 ± 6.43 and 16.19 ± 16.54 months respectively.
Conclusion. The effectiveness of neoadjuvant chemohormonal therapy for high risk prostate cancer can be assessed by the features of pathologic response through ABC system which has demonstrated own versatility and reproducibility in presented material. Neoadjuvant therapy with docetaxel and degarelix can improve the treatment outcomes of prostate cancer patients at high and very high risk of disease progression. The data on changes in the prostate tissue can be helpful in predicting the duration of the effect after chemohormonal therapy with subsequent surgery.

90-101 712
Abstract

Objective: to study the clinical and demographic profile of patients with non-metatstatic castration-resistant prostate cancer (nmCRPC) and clinical approaches to the treatment of nmCRPC in the context of daily medical practice before and after progression M1 stage.
Materials and methods. The multicenter non-interventional epidemiological study is planned to include 200 patients with a documented diagnosis of nmCRPC from 2019 to 2020. The interim report has included data on 108 patients from 13 centers located in different regions of the Russian Federation. The median age of the patients was 73 (55—90) years.
Results and conclusion. When the diagnosis of nmCRPC was made, the median prostate specific antigen was 8.23 (0.17—116.9) ng/ml, and the prostate specific antigen doubling time was 6 (1—50) months. When diagnosed nmCRPC, 86 patients (79.6 %) underwent a change of therapy, of which 42 % were prescribed modern regimens containing the new generation non-steroid antiandrogens (apalutamide, enzalutamide).

102-108 676
Abstract

Materials and methods. In our study, 21 patients with recurrent prostate cancer after radical prostatectomy and oligometastases were treated by salvage radiation therapy, which included radiotherapy treatment of recurrent tumors, regional pelvic lymph nodes, the prostate bed and stereotactic body radiation therapy to detected solitary metastases.
Results. The average follow-up period was 19 ± 3.5 months. At the same time, 12 (57 %) of 21 patients are currently under observation for more than 1 year, and 1 patient for more than 5 years without signs of a biochemical recurrence. The indicator of biochemical control of the disease was 86 % (18 / 21 patients) with an average follow-up period of 19 months.
Conclusion. It seems to us that further study of this problem can replace today's palliative standard of treatment for this special category of patients — hormonal and chemotherapy treatment, which has low effectiveness at a high incidence of toxicity.

109-116 660
Abstract

Background. Prostate cancer (PCa) is the second most common cancer in men. Currently there is no clear understanding of preferences among oncologists in Russia in decision-making process regarding adjuvant ADT in patients with locally advanced PCa with high and very high risk of recurrence after prostatectomy or radiotherapy.
Objective: to provide accurate and reliable information regarding the adjuvant endocrine treatment in patients with locally advanced PCa in the Russian routine clinical practice.
Materials and methods. This multicentre, non-interventional, prospective observational cohort study included 204 males (mean age 64.9 ± 6.2 years) with locally advanced PCa. The patients were enrolled at 18 sites in Russian Federation. Information on the routine diagnosis-specific examinations, including PSA measurements before, after and during one year after prostatectomy / radiotherapy was collected. Information regarding patient demographics, disease characteristics, management approaches, diagnostic tests and medications received by patients was taken from the medical records.
Results. Among patients participated in the study, 64.4 % were treated surgically, and 38.6 % underwent radiotherapy; only 6 patients (4.6 %) underwent radical prostatectomy followed by radiotherapy. Median duration from diagnosis of PCa at the time of enrolment was less than 2.7 months, for 75 % of patients the disease duration did not exceed 7 months. ADT was used in 132 patients. ADT was received by 95.8 % of males treated with radiotherapy without radical prostatectomy and by 46.8 % of those who underwent radical prostatectomy without radiotherapy. Medical or surgical castration was used in 56.4 % of cases, antiandrogens without castration were used by less than 10 % of patients, while 28.2 % of patients received treatment with both castration and antiandrogens and the same number of males underwent only castration. Percentage of patients with PCa progression was 9.3 % for males after radical prostatectomy without radiotherapy and 7.4 % for those who underwent radiotherapy without radical prostatectomy. There were no cases of death due to PCa progression.
Conclusion. The results are in alignment with international guidelines and standards. Received data can help to improve management approaches for treatment of Russian patients with high risk locally advanced PCa, particularly giving a basis for a decision on use of ADT.

REVIEW

153-164 1084
Abstract

A review of the literature is devoted to the urgent issue of modern oncourology — the treatment of prostate cancer using high-intensity focused ultrasound (HIFU). Currently, there is a trend in shifting the approach from total to focal ablation in patients with prostate cancer of low risk in order to reduce the profile of complications. The article presents the results of modern research on HIFU in both total and focal ablation. Data on oncological, functional results of treatment are given.

165-173 800
Abstract

Prostate cancer is one of the most common forms of malignant neoplasms in men. In this regard, it is relevant to search for diagnostic markers that allow the creation of inexpensive, effective tests for early diagnosis of the disease, predicting the risk of relapse and assessing the effectiveness of the therapy. Existing invasive methods for diagnosing prostate cancer present some difficulties for patients. This article discusses the diagnostic capabilities of tissue biomarkers of prostate cancer obtained by non-invasive methods.

174-189 537
Abstract

Early diagnosis of renal cancer carcinoma is a key determinant of patient survival. The asymptomatic disease course and lack of reliable diagnostic markers lead to the fact that more than 30 % renal cancer cases discovered at an advanced stage, when the prognosis is poor because kidney tumors are resistant to standard chemotherapy and radiation. More than 30 % of renal cancer carcinoma recur or metastasize after surgical treatment. Despite the implementation of novel targeted drugs and immune point inhibitors, the 5-year survival rate for metastatic renal cancer carcinoma remains dismal. Unsatisfactory result of renal cancer treatment may be caused by high inter- and intra-tumor heterogeneity and tumor evolution during therapy, as well as the lack of predictive and on-treatment monitoring biomarkers. Liquid biopsy test that utilizes free-circulating DNA (cfDNA) in the blood of patients, opens up new opportunities for managing patients with renal cancer. The diagnostic and predictive potential of these minimally invasive biomarkers has been demonstrated for various types of cancer. The use of highly sensitive methods of cfDNA analysis may allow early cancer detection and prediction of postoperative disease recurrence before dinical and radiographic progression. Serial cfDNA samples, that were collected before and during course of treatment, can provide information about the dynamic mutational changes in the volume of the entire tumor and metastases in real time, and the emergence of drug resistance during treatment. This information may be promising toolfor optimizing patient-specific therapeutic strategies. This review is focusing on the potential clinical application of cfDNA from blood in renal cancer.

 

190-197 832
Abstract

Prostate cancer is one of the most common urological malignancies. Improved diagnostic methods and widespread implementation of mandatory prostate specific antigen (PSA) testing in a number of clinics have led to an increase in the number of timely diagnosed cases of localized and locally advanced prostate cancer, as well as to the expansion of indications for radical therapies. Nevertheless, 30 % to 50 % of patients (depending on their risk) develop biochemical relapse after surgery or radiotherapy. Non-metastatic castration-resistant prostate cancer is usually a result of disease progression after radical treatment and long-term androgen-deprivation therapy, which manifests by constant increase in the PSA level along with castrate level of testosterone and no distant metastases according to the results of comprehensive radiological examination. A number of large clinical studies have demonstrated that regular examinations and control of PSA doubling time (main prognostic factor associated with poor disease outcome) are crucial to increase survival and prevent the development of distant metastases.
This paper aims to provide an overview of existing literature on the problems associated with diagnosis and treatment of non-metastatic castration-resistant prostate cancer. We have analyzed large randomized studies that demonstrated an increase in the overall survival of patients receiving selective androgen receptor antagonists.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

117-125 2026
Abstract

Objective: to identify the role simultaneous use of the Vesical Imaging-Reporting and Data System (VI-RADS) and the assessment of serum levels of several mediators and growth factors for the evaluation of metastatic process and disease stage in patients with bladder cancer.
Materials and methods. This retrospective study included 85 patients with histologically verified transitional cell (urothelial) bladder carcinoma (stages рТа—TINOMO. [)T2NOMO, рТ3—4NN0M0, and [)T2—4N1—3M1) and 20 healthy controls. In addition to general clinical examinations, all patients have undergone preoperative diffusion-weighted magnetic resonance imaging of the pelvis with background suppression. We calculated the diffusion coefficient and included it into the VI-RADS protocol. All study participants were also tested for their serum levels of vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), monocyte chemoattractant protein 1 (MSP-1), interferon γ (IFN-γ), transforming growth factor β1 (TGF- β1), granulocyte colony-stimulating factor (G-CSF), and granulocyte-macrophage colonystimulating factor (GM-CSF) using enzyme-linked immunosorbent assay (ELISA).
Results and conclusion. We found that the preoperative use of VI-RADS together with the assessment of serum levels of pro-inflammatory mediators, colony-stimulating factors, and growth factors in patients with muscle-invasive bladder cancer provide additional information about the activity of malignant transformation in tumor tissue and tumor spread. Their simultaneous use during the examination of patients with muscle-invasive bladder cancer is a promising diagnostic approach to monitor treatment response.

126-134 871
Abstract

Objective: to compare recurrence rate, progression rate and recurrence-free survival in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) after adjuvant intravesical chemotherapy (IVCT) with titanium glycerosolvate aquacomplex (TGA) versus intravesical BCG therapy.
Material and methods. In a retrospective multicenter clinical study initially were included 126 patients with NMIBC. Of all 126 patients, 94 patients with high-risk NMIBC were selected and divided into 2 groups using a pseudo randomization with propensity score matching to minimize systematic differences in the process of forming groups. The treatment group (n = 55) consisted of patients with high-risk NMIBC who received a 6-week course of adjuvant IVCT with TGA. In the control group (n = 39) patients received an induction 6-week course of adjuvant intravesical BCG therapy, 19 (49 %) of 39 patients received maintenance therapy. Both methods were compared according to recurrence rate, progression rate and recurrence-free survival. Significance of difference was set at p <0.05.
Results. The compared groups of patients were well balanced in terms of clinical and morphological characteristics and the main risk factors for recurrence and progression of non-muscle-invasive bladder cancer, no significant differences were found between the groups (p >0.5). The recurrence rate in treatment and control groups was 33 % and 23 %, respectively (p = 0.31). The disease progression was observed in 1 (2 %) patient in the treatment group and in 4 (13 %) patients in the control group (p = 0.08). The median disease-free survival in both groups of patients was not reached at the time of analysis. Three- and five-year recurrence-free survival in the treatment group of patients were 71 % and 62 %, respectively; in the control group — 76 % and 72 %, respectively. There were no significant differences between recurrence-free-survival curves of the treatment and control groups (p = 0.58).
Conclusion. Adjuvant IVCT with TGA has demonstrated a clinical effectiveness comparable to intravesical BCG therapy and it can be used as an alternative method of treatment in patients with high-risk NMIBC.

135-142 538
Abstract

Objective. There is the second generalized analysis of administration of vinflunine in real clinical practice in Russia.
Materials and methods. This analysis gathered 15 patients with urothelial carcinoma treated using this medicine in 8 cancer centers in Russia. We assessed efficacy, safety profile of vinflunine in this subset of patients.
Results. Clinical efficacy of vinflunine (complete response + partial response + stable disease) was 73.3 %, one patient demonstrated complete response. Median of response duration accounts for 3.8 months. Six-month and 1-year survival rate made up 93.3 %. Adverse events were observed in 53.5 %, with only one episode of neutropenia 4 grade.
Conclusion. In our second analysis vinflunine was more effective than in randomized clinical trial and other studies from real practice in Europe. Thus, we confirm expediency to administer of vinflunine for metastatic urothelial carcinoma.

UROLOGICAL COMPLICATIONS IN CANCER PATIENTS

143-152 709
Abstract

In recent years, significant changes have taken place in the treatment of prostate cancer. Modern radiation treatment technologies are beginning to take a leading position not only in localized and locally-advanced forms of the disease, but also in the case of oligometastatic process. This encourages a natural interest in various aspects of radiation therapy of prostate cancer, in particular its effects on erectile function status. Analysis of domestic literature shows the complete absence of publications on the technical possibilities of radiation therapy to preserve potency after treatment. The purpose of this work was to highlight this critical issue.

CLINICAL CASE

198-204 776
Abstract

Urothelial transitional cell cancer in developed countries is the 4th most common. In terms of frequency, it is outstripped only by prostate, breast, lung, and colorectal cancer. In the vast majority of cases, urothelial carcinoma develops in the bladder. It accounts for 90—95 % of all cases of transitional cell cancer of the urinary tract. Much less often, in 5—10 % have to deal with its localization in the upper urinary tract (in the calico-pelvic system or ureter). In 17 % of upper urinary tract cancers, bladder cancer is simultaneously diagnosed. The incidence of urothelial transitional cell cancer has increased over the past few decades as a result of improved diagnosis and improved survival of patients with this nosology. The use of modern, high-tech equipment for visualization and direct surgical intervention contributes to such results. The use of laser energy as the main tool for tissue dissection in endoscopic oncourology reveals the undeniable advantages of this method in comparison with the traditional electrosurgery.
We present a clinical observation of the diagnosis and surgical treatment of urothelial bladder cancer with invasion of the ureter, performed by en-bloc tulium laser. An operation was performed-transurethral resection of a urothelial bladder tumor with invasion of the ureter, performed by en-bloc tulium laser. Intraoperatively, ureteropieloscopy was performed, and the tumor did not spread to the upper urinary tract beyond the intramural part of the ureter. Thanks to the precision of the action of the tulium laser on the tissue, not resection, but, in fact, dissection of the bladder wall, a high-quality macropreparation was obtained, which made it possible to establish a final diagnosis. Histological conclusion: from the bladder — non-invasive urothelial cancer G2-3; from the mouth of the left ureter — fragments of fibrous tissue lined with urothelium from atypia. 3 months after the operation — no recurrence of urothelial cancer was revealed, which indicates a high quality of the operation.
This clinical observation demonstrates the superiority of laser en-bloc dissection compared to the treatment of bladder tumors. Obtaining a macro-product of urothelial transitional cell cancer of the highest quality can contribute to avoiding unjustified radical nephrureterectomies and conducting organ-preserving treatment, for absolute and elective indications. The 1.94 µm Tulium Erbium laser is an effective tool for performing minimally invasive transurethral interventions in non-invasive bladder cancer.

ТОЧКА ЗРЕНИЯ

205-208 1079
Abstract

Patients who practice Islam often refuse the proposed type of treatment for malignant neoplasms, citing religious reasons. Most fear that complete or partial non-retention of urine, the presence of a urostoma (ileal conduit) will violate their ritual purity and, as a result, their religious duties. The consequence of such refusal of treatment may be a lower quality of life, compared with patients of other faiths. Unfortunately, a low awareness of religious responsibilities among surgeons performing pelvic exentesis, cystectomy, prostatectomy, may prevent a full-fledged discussion of these issues before surgery. The presented review of the literature examined studies, legal aspects, and religious arguments that assist doctors in choosing treatment tactics for patients.

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ISSN 1726-9776 (Print)
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