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Cancer Urology

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Vol 13, No 4 (2017)
View or download the full issue PDF (Russian)
https://doi.org/10.17650/1726-9776-2017-13-4

REVIEW

111-121 1372
Abstract
In the era of personalized treatment, oncologists are striving to tailor medical treatment to the characteristics of the individual patient, emphasizing the importance of a continuous search for accurate biomarkers. Prognostic biomarkers reflect the intricate underlying biology that enables cancer to progress. Intratumoural heterogeneity includes genetic, epigenetic and functional heterogeneity. Genetic intratumour heterogeneity is a consequence of clonal evolution and a cause of desease progression. Herewith specific mutations are associated with particular stages of tumour development, correlates with specific histopathological disease stages. Many patients with prostate cancer have disease recurrence after resection of the tumor despite adjuvant therapy, while some patients dont have a relapse despite the absence of treatment. So the reassessment of the current criteria and better prognostic and predictive biomarkers for the selection of patients who might benefit from adjuvant chemotherapy are urgently needed. A prognostic biomarker reflects the natural history of the tumor and provides information on the likely outcome and prognosis, independent of a specific treatment. Predictive biomarkers indicate the sensitivity or resistance of the tumor to a given treatment. Some markers can be both prognostic and predictive. Gene mutations and epigenetic changes that modify the intracellular signaling pathways may be important factors in oncogenesis. In this context, oncogenes, genes-tumor suppressors and miRNAs have attracted attention as potential biomarkers and regulators of oncogenesis and evaluate in clinical trials.

LECTURE

16-24 1075
Abstract
Immune-checkpoint inhibitors blocking the programmed death 1/programmed death-ligand 1 (PD-1/PD-L1) and cytotoxic T-lymphocyteassociated protein 4 (CTLA-4) have shown a prominent anti-tumor activity with long-term responses and an acceptable toxicity profile  in clinical trials. Pembrolizumab, atezolizumab, nivolumab, avelumab, and durvalumab are anti-PD-1/PD-L1 agents that redefine the standard of care for advanced urothelial carcinoma. CTLA-4 inhibitors are also under investigation in this setting. Phase III trial KEYNOTE-045 has demonstrated significant survival benefit in patients treated with pembrolizumab comparing with the standard second-line chemotherapy. Atezolizumab, nivolumab, avelumab, and durvalumab were also recommended for platinum-pretreated urothelial carcinoma patients based on phase II data. Following investigations of biomarkers such as PD-L1 expression are needed to determine high-responders to immunotherapy. This review article describes the advances in immunotherapy with immune-checkpoint inhibitors.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

25-33 853
Abstract

Objective: to investigate the time course of changes in the early biomarkers of acute kidney injury in patients with clinically localized cancer during partial nephrectomy, as electively indicated, under thermal ischemia with prior epidural block.

Materials and methods. To analyze the nephroprotective effect of an epidural block in kidney resection with warm ischemia, markers of acute kidney injury (cystatin C, interleukin 18, NGAL, L-FABP and KIM-1) were studied by ELISA in the blood and urine of 35 patients with local cancer with an epidural block (main group) and 37 patients with local cancer without an epidural block (control group) before surgery and 40 min after its beginning and on days 1 and 3 of the postoperative period. All patients were divided into 2 groups by the levels of cystatin C in the blood serum: 1000 ng/ml and lower, and over 1000 ng/ml.

Results. Epidural block during the perioperative period in kidney resection with warm ischemia for patients with local cancer had an obvious nephroprotective effect allowing maintaining the initial renal functional parameters, in contrast to the standard disease management.

34-39 943
Abstract

Objective is to investigate the results of laparoscopic resection of tumors of the upper pole of the kidney using the method of renal rotation around its vessels.

Materials and methods. The analysis included results of surgical treatment of 12 patients with tumors of the upper pole of the kidney who underwent laparoscopic partial nephrectomy with rotation around the vascular pedicle. The kidney and its vessels were mobilized transperineally, then the kidney was rotated around its vessels in such a way that the upper pole containing the tumor was located in place of the lower pole. In this technique, dorsally located tumor was positioned frontally after rotation, making its subsequent resection more manageable. After tumor removal and hemostasis, the kidney was returned to its normal position.

Results. Using this technique, laparoscopic nephrectomy was possible in all patients. Mean duration of laparoscopic partial nephrectomy was 120.0 ± 35.0 (90–210) min, warm ischemia time – 14.5 ± 7.8 (10–26) min, blood loss – 120.0 ± 65.5 (60–300) ml. Pathomorphological examination revealed renal cell carcinoma in 11 (91.7 %) patients, renal angiomyolipoma – in 1 (8.3 %) patient. Follow-up duration was 6–24 months; during this time no local recurrence or distant metastasis were observed.

Conclusion. Use of renal rotation around its vascular pedicle expedites laparoscopic transperineal resection of dorsally located tumors of the upper pole and minimizes the number of intra- and postoperative complications.
40-44 1168
Abstract

Background. In a CRAD001LRU02T study of everolimus for metastatic renal cell carcinoma patients previously treated with bevacizumab ±  interferon, median overall survival (OS) was 17.4 months (95 % confidence interval 13.5–21.3 month).

Objective of final analysis was to evaluate 5-year OS and long-term toxicity in this study.

Materials and methods. Survival data were collected from 37 patients with bevacizumab-refractory metastatic renal cell carcinoma who received everolimus in a completed prospective multicenter study. Patients were predominantly male, 89 % had ECOG performance status of 0/1, 51 % received previous bevacizumab in combination with interferon, and 38/62% had MSKCC favorable/intermediate risk disease.

Results. The 5-year survival rate was 16.2% (95 % confidence interval 14.1–18.3 %), with a median follow-up of 5 years. The 1-, and 3-year OS rates were 81.0 and 43.0 %, respectively. The median duration of second-line of everolimus was 315 (range 61–569) days. 11 (29.7 %) patients received third-line therapy with a median duration of 3.6 months. Confirmed objective tumor responses were seen in 5 (14.0 %) patients. 70.0 % (n = 26) patients had a stable disease. 1 (2.7 %) patient achieved complete response after 4 years of therapy. One (2.7 %) patient  discontinued everolimus therapy on their own accord due to relapse of systemic lupus erythematosus and one (2.7 %)  patient had 14-days interruption of an everolimus therapy due to grade 3 hyperglycemia. No grade 4 treatment-related toxicity was found.

Conclusions. Everolimus provided an estimated 5-year survival rate of 16.2 % for bevacizumab-resistant metastatic renal cell carcinoma. Prolonged everolimus was not associated with new types or increased severity of adverse events.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

45-50 1036
Abstract
We performed genome-wide transcriptome meta-analysis of prostate cancer samples after radical prostatectomy of patients without lymph node metastasis. Significant associations were determined between expression of platelet-derived growth factor alpha and beta genes (PDGFRA and PDGFRB) and probability and time of onset of biochemical recurrence.
51-54 786
Abstract

Background. The high rates of prostate cancer (PC) morbidity and mortality, as well as their high growth rates suggest that investigations of the nature of PC are of importance. The possible association of PC with high-risk human papillomaviruses (HPV) remains open.

Objective: to examine surgically removed prostate tissue from patients with PC for HPV 16 type E7 oncogene, the main type of HPV being responsible for cervical cancer.

Materials and methods. Polymerase chain reaction was used to test the prostate tissues removed from 17 patients with PC during radical prostatectomy. Cryopreserved (formalin- and paraffin- untreated) tumor samples were employed for better preservation of DNA. The multifocal growth pattern typical of PC was taken into account using microdissection to accumulate homogeneous prostate cancer, dysplastic, and intact epithelial cells.

Results. HPV 16 type E7 oncogene DNA was detected in the samples from 7 patients with PC out of the 17 examinees, including all 5 cases where DNA had been isolated from the homogeneous regions of PC.

Conclusion. The finding may suggest that HPV 16 is frequently present in the prostate glands of Russian patients with PC.
55-63 1472
Abstract
Focal therapy is a promising option for localized prostate cancer treatment in low and intermediate risk patients. The combination of minimal invasiveness, disease control and the possibility of re-treatment in case of recurrence have significantly increased interest in focal therapy. However, before the final introduction of focal therapy into clinical practice, a number of significant limitations have yet to be overcome, such as patient selection, visualization of target, the choice of the treatment modality and the surgery planning, as well as the development  of a follow-up protocol. Studies have shown that focal therapy has minimal impact on the quality of life, but its oncological effectiveness has yet to be evaluated in comparison with radical methods of treatment.
64-69 912
Abstract

Background. The rate of prostate cancer progression after radical treatment is about 40 %. Currently, some data suggest that patients with oligometastases have a more favorable prognosis than patients with extensive tumor lesions. In 78 % of cases, oligometastases are localized  in the pelvic and retroperitoneal lymph nodes. Surgical removal of all detectable metastases can cure prostate cancer recurrence, however  the possibility of using salvage lymph node dissection (sLND) in clinical practice remains limited due to the lack of data on surgical and oncological outcomes of this treatment method.

The study objective is to evaluate surgical and early oncological outcomes of sLND in patients with progressive prostate cancer after radical treatment.

Materials and methods. The study was conducted at the N.N. Blokhin National Medical Research Center of Oncology. The analysis included 17 patients with biochemical prostate cancer recurrence and symptoms of lymphogenic disease progression based on positron emission tomography/computed tomography with radiopharmaceuticals 18F-choline (n = 14; 82.35 %) and 68Ga-prostate-specific membrane antigen (n = 1; 5.88 %) and magnetic resonance lymphography with Combidex (ultra-small superparamagnetic iron oxides, USPIO) (n = 2; 12.0 %). All patients underwent sLND in the period from October of 2014 to December of 2016.

Results. Postoperative complications were observed in 58.8 % (n = 10) of cases. No grade III and IV complications per the Clavien–Dindo classification were registered. For median follow up duration of 17.5 (5–31) months, full biochemical response in the form of decreased prostate-specific antigen < 0.2 ng/ml was observed in 5 (29.4 %) patients. Mean time to prescription of hormone therapy was 6.6 (1–12) months. Considering this follow up duration, 53 % of patients hadn’t received hormone therapy.

Conclusion. Therefore, sLND is a safe surgical intervention with low number of severe complications. sLND can be successfully used in wellselected patients as a diagnostic tool and provide accurate information on the state of lymph nodes. Removal of oligometastases allows  to achieve long-term relapse-free period in individual patients and postpone prescription of hormone therapy.
70-78 1712
Abstract

Background. The highest rate of incontinence after radical prostatectomy (RP) is observed in the first 2–6 months after surgery. In order  to decrease the period of incontinence, virous surgical methods aimed at preservation and reconstruction of structures participating  in the mechanism of urine retention has been developed and improved.

The study objective is to evaluate effectiveness of an original method of formation of an urethral anastomosis in the early continence recovery.

Materials and methods. Data on 126 patients who underwent retropubic RP were analyzed. Depending on the method of urethral anastomosis formation, patients were divided into 2 groups: in the 1st group (n = 52) the patients underwent PR with urethra suspension m. levator ani, in the 2nd (n = 74) – standard RP. In the 1st group, 6 ligatures were applied to the anterior and posterior urethra walls: at the 12 and 6 hour projections through the mucosa, submucosa, and smooth muscle; at the 10, 2, 4, and 8 hour projections – more laterally with capture of the m. levator ani medial margins. Continence recovery was evaluated on days 1, 7, and 14 after urinary catheter removal and then at days 30, 90, 180, and 365 after RP. The criteria of continence were absence of urine leakage at rest and during physical activity and a necessity of using a safety liner.

Results. There weren’t any significant differences at day 1 after urinary catheter removal between the two groups (р > 0.05). In the 1st group, continence values at days 30, 90, and 180 after RP were significantly higher (57.7, 69.2, and 71.1 %, respectively) compared to the 2nd group (35.1, 41.9, and 51.3 %, respectively) (р <0.05).

Conclusion. Results of this work show significant benefits of RP with urethra suspension m. levator ani compared to standard RP per continence recovery criteria at days 7, 14, 30, 90, and 180 after the surgery. The technique of urethra suspension m. levator ani is easy to perform and ensures early continence recovery after RP.
79-84 1029
Abstract

Objective is study on the clinical efficacy of the treatment method using polychemotherapy in the docetaxel + vinorelbine regimen in patients with prostate cancer of stage III–IV without distant metastases.

Materials and methods. The study included 112 patients, who underwent radical prostatectomy on prostatic adenocarcinoma in the period 2006–2010 at N.N. Alexandrov National Cancer Center of Belarus.

Results. The developed scheme of chemotherapy after radical prostatectomy showed its effectiveness in patients with the spread of a tumor characterized by the criterion pT3b–4pN0  or pT3apN0 with Gleason sum ≤7 and prostatic specific antigen level before operation >20 ng/ml. In patients with pT3aN0 tumor with a Gleason sum ≤7 and prostatic specific antigen level before surgery <20 ng/ml, adjuvant chemotherapy is not justified.
85-90 807
Abstract

Hormone therapy of metastatic prostate cancer (mPC) has been the “golden standard” of treatment since 1941. However, survival rates in patients with this pathology have remained low. Based on the results of newer studies, early start of docetaxel chemotherapy or antiandrogen abiraterone therapy in combination with standard hormone therapy allows to significantly increase survival of patients with mPC. In this review, data from these studies and advisability of docetaxel and abiraterone at the 1st line therapy of mPC are discussed.

91-100 2642
Abstract

Background. Castration-resistant prostate cancer (CRPC) is wide-spread severe disease in many regions of the world. Enzalutamide, abiraterone and cabazitaxel have been recently registered for the treatment of this condition.

Objective: to perform indirect comparison of enzalutamide, abiraterone and cabazitaxel efficacy and safety in 2nd line “post-docetaxel” treatment of CRPC according to published clinical data.

Materials and methods. Indirect comparison was undertaken to extract efficacy and safety parameters of enzalutamide, abiraterone and cabazitaxel from integrated registration pivotal trials and independent retrospective studies. 13 articles were selected: enzalutamide – 2, abiraterone – 7, cabazitaxel – 3 and orteronel 1 article.

Results. Enzalutamide had highest chances of prostatic specific antigen response (50 % and more decline from baseline) and highest chances of Response Evaluation Criteria In Solid Tumors (RECIST) soft-tissue objective response. Chances of enzalutamide and abiraterone adverse effects did not have serious difference from control groups in pivotal trials. Cabazitaxel increased adverse effects chances, mostly hematological adverse effects.

Conclusion. Treatment with enzalutamide of CRPC in 2nd line “post-docetaxel” provided best parameters of prostatic specific antigen response. Enzalutamide is safer than cabazitaxel and does not have several adverse events typical for abiraterone.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER

101-106 818
Abstract

Background. This article presents clinical cases of bladder cancer (BC) developed after previous irradiation and diagnosed in flat suspicious area by cross-polarization optical coherence tomography (CP-OCT) based on analysis of characteristics of scattered light, and with histological material confirmed by nonlinear microscopy.

Objective: to present clinical cases and features of BC diagnosis in presence of radiation-induced changes.

Materials and methods. Intra-vitam examination of the bladder mucosa was performed using the OKT 1300-U system (Institute of Applied Physics of the Russian Academy of Sciences, Nizhniy Novgorod). Areas that appeared malignant per CP-OCT data were biopsied. Apart from traditional examination of histological samples with hematoxylin and eosin staining, tissue samples were analyzed using nonlinear microscopy in the mode of second harmonic generation (collagen state analysis) and emission of two-photon fluorescence excitation (elastin state analysis).

Results are presented through 2 cases of BC in patients with side effects of radiation therapy of varying severity. CP-OCT allowed in-life differentiation of areas of post-radiation inflammatory changes and malignant tumors developed as a result. Nonlinear microscopy provided information on the state of connective tissue matrix of the bladder in the context of radiation changes and transition to tumor.

Conclusion. Radiation changes of the bladder mucosa, especially severe ones, can conceal development of malignant tumors. Use of optical methods helps in differential diagnosis of cancer and post-radiation changes of the bladder. CP-OCT is an optimal noninvasive method of examination of the bladder mucosa during cystoscopy. Demonstration of clinical material is aimed at practicing urologists to increase their vigilance in relation to possible BC in patients who underwent radiation therapy of the organs of the lesser pelvis.

CLINICAL CASE

122-125 933
Abstract
Kidney transplantation is the most frequently performed organ transplant procedure in the world. The occurrence of malignant tumors is one of the well-known late complications of organ transplantation, which is induced by immunosuppressive therapy. In the vast majority of patients, kidney cancer occurs in the native organs; however, in a small percentage of cases, malignancies are found in the graft organ. The article describes a rare clinical case of a patient with synchronous cancer in the native and graft kidneys.
126-132 812
Abstract
Renal cell carcinoma (RCC) is rare in children, its metastatic form is even rarer. At present there is no treatment protocol for children with RCC. This clinical observation presented the patient 10 year old with RCC metastases to the lungs. After radical surgery, after targeted sorafenib therapy the patient has a positive dynamics. At present his progression-free survival is 30 months.

CONGRESSES AND CONFERENCES

133-140 1033
Abstract
The European Society for Medical Oncology (ESMO) Congress in partnership with the European Association for Cancer Research took place between September 8th and 12th of 2017 in Madrid. In 42 years of its existence, the forum has grown from a regional educational meeting in Europe to the main international event in oncology. The key topic of this Congress was integration of molecular biology knowledge with clinical specialties. The ESMO 2017 Congress united almost 24,000 professionals of various fields from 131 countries who submitted 1736 abstracts. More than 50 scientific abstracts which were deemed worthy of special discussion and capable of changing current clinical practice, were separated into a category of late-breaking abstract (LBA). This review highlights some important topics of oncological urology that were discussed at the ESMO 2017 Congress.

ANNIVERSARIES

DIAGNOSIS AND TREATMENT OF URINARY TRACT TUMORS. CANCER OF THE URETHRA AND PENIS

107-110 1037
Abstract

Penile tumors are usually presented by squamous cell carcinoma arising from the foreskin epithelium or glans of the penis. Other types of tumors are relatively rare that is why the diagnosis and treatment algorithms of them are understudied. Here we report a case of the surgical treatment of the patient with rare vascular tumor (hemangiopericytoma) arising from the corpora cavernosa of the penis. This is an exceptional site for this rare tumor with absence of previously reported cases in the published literature.



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