Цель исследования – разработка и валидация номограммы, позволяющей прогнозировать 12-месячную выживаемость без прогрессирования (ВБП) у пациентов, получающих пазопаниб в качестве первой линии терапии распространенного рака почки.

Материалы и методы. Проведено статистическое моделирование данных 557 пациентов, получавших пазопаниб, в исследовании III фазы COMPARZ. Известные прогностические факторы были внесены в мультивариантную модель по Cox. Рассмотренные параметры включали уровень нейтрофилов, содержание альбумина и щелочной фосфатазы в сыворотке, время между постановкой диагноза и началом лечения, а также наличие костных метастазов. Для валидации были использованы данные по группе участников плацебоконтролируемого исследования III фазы, получавших пазопаниб.

Результаты. Данная модель включала 10 прогностических факторов, представленных в виде номограммы, позволяющей прогнозировать 12-месячную ВБП. Сопоставления, проведенные с целью калибровки разработанной модели, позволяют предполагать достаточное соответствие расчетных вероятностей ВБП ее фактическим показателям. Индекс конкордантности для 12-месячной ВБП составил 0,625. Отмечена достоверная взаимосвязь (p < 0,05) между ВБП и наличием костных метастазов, интервалом времени между постановкой диагноза и началом лечения, а также уровнями альбумина и щелочной фосфатазы. Прогностическая роль последних 2 параметров оказалась весьма существенной.

Выводы. Номограмма позволяет с достаточной точностью прогнозировать ВБП у пациентов с распространенным раком почки, получающих пазопаниб, в зависимости от исходных клинических характеристик.

Non-clear cell renal cell carcinoma has various histologic subtypes. Tumor biology plays significant role in the disease development. However, despite the one surgical approach both to clear cell and non-clear cell renal carcinoma, patients’ outcomes within one stage of the disease may vary. Furthermore, tumor sensitivity and its response to therapy are highly dependent on the same histologic subtype.

The article gives detailed data on the current treatment of papillary, chromophobe and other histologic subtypes of renal cell carcinoma.

Background. Thorough study of the molecular genetic alterations in patients with hereditary and sporadic renal cell carcinoma (RCC) enabled to reveal potential therapeutic targets - vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), growth factor receptors (VEGFR, PDGFR, EGFR, FGFR), mTOR signaling protein. Advances in targeted therapy treatment in the current therapeutic practice have brought a problem of its rational use and ultimately effective outcomes. The main solution of solving this problem is to establish independent clinical and laboratory prognostic factors and molecular markers which could predict the efficacy of targeted therapy.

Objective – optimization of targeted therapy in patients with RCC by using both molecular and genetic prognostic factors as predictors of the treatment efficacy.

Materials and methods. We assessed the level of mRNA expression of 13 potential target genes in primary tumor and metastatic site of patients suffering from metastatic RCC (n = 43) and evaluated the influence of the selected genes’ expression on the therapeutic efficacy of mTOR inhibitors and VEGFR inhibitors.

Conclusion. VEGFR1 mRNA overexpression in metastatic site as well as mTOR and/or PI3K mRNA overexpression could be assessed as potential biomarkers in predicting the treatment efficacy of VEGFR inhibitors and mTOR inhibitors respectively. The higher expression of RAF1 mRNA and mTOR signaling pathway are not typical molecular alterations in patients with mRCC. RAF1 mRNA overexpression in metastatic site as well as activation of the alternative signaling pathway (RAS-RAF-MAPK) in tumor cell are negative prognostic factors of the efficacy of targeted therapy. Activation of the signaling RAS-RAF-MAPK pathway in tumor cells is probably an alternative independent mechanism that “drives” tumor development in certain groups of patients.

Background. Due to the currently accepted operative technique of the transurethral resection (TUR) of bladder, during the surgery we obtain a histological material that is multiple pieces of the tissueof exophytic area of tumor, the bladder base and the bladder wall, in which a specialist histologist can be guided only with careful labeling, and the correct pathologic diagnosis is possible only in case of the presence of all layers of the bladder wall in the preparation. The performanceof TUR of bladderen blochas allowed visualizing an additional morphological feature in the preparation – its own muscularis mucosa.

Objective. The evaluation of effectiveness of the transurethral surgical treatment of thepatients with superficial bladder cancer by comparing the immediate and long-term results of the standard TUR and the TUR of bladder wall tumor en bloc. The assessment of the role of the tumor invasion of propermuscularis mucosa in the prediction of recurrence and progression of superficial bladder cancer.

Materials and methods. We analyzed the results of the examination and treatment of 270 patients with newly diagnosed «bladder cancer» who were treated between 2003 and 2012. All patients were divided into 2 groups: the main group (n = 94) who underwent the transurethral resection of the wall bladder tumor en bloc, and the compared group (n = 176) who underwent the standard transurethral resection. As a result wehave evaluated the role of the tumor invasion of propermuscularis mucosa in the prediction of recurrence and progression of superficial bladder cancer.

Results and conclusions. The technique of the operation affects the recurrence rate by reducing it from 47.7 % in cases of the standard TUR to 34 % in cases of the TUR en bloc (p < 0.05), and also affects imperceptibly the terms before the recurrence (p > 0.05). The application of the TUR en bloc reduces the frequency of progressionby 4 times (p < 0.001) and increases the termsbeforethe progression by almost 2 times (p < 0.05). It allows to reduce the recurrences in the area of the resection to a minimum and to increase the periods before the occurrence of relapse. The presence of the damage ofproper muscularis mucosa (the in-growth or invasion, the categories T1b and T1c) increases the frequency of relapses for more than 2 times, and the way out of the tumor outside the layer of proper muscularis mucosareduces the term of relapse by 2.5 times, the progression rate increases from 2 % to 22.7 % and 18.5 %, and the average time before progression reduces from 41.5 to 26.0 and 17.1 with increase of the depth of tumor invasion with categories T1a, T1b and T1c respectively.

Background. Cystic-glandular cysititis is defined as cystic formation of the urothelial nests which may be associated with inflammatory conditions as well as neoplastic processes.

Objective – to establish a relationship between cystic-glandular cysititis and bladder cancer.

Materials and methods. We conducted a retrospective study using data of 52 patients who’d been diagnosed with cystic-glandular cysititis of common or intestinal type in the period between 2006 and 2014. The patients’ information regarding age, gender, type of histological material (biopsy or transurethral resection of bladder), urological anamnesis has been analyzed. Follow-up duration included cystoscopy performance with bladder biopsy and varied from 1 to 8 years.

Results. Patients suffering from diagnosed cystic-glandular cystitis were between the ages of 27 and 89 years old, with a higher prevalence rate, 2:1, in men to women. Intestinal metaplasia was revealed in 7 (14 %) out of 52 patients. Thorough study of the urological anamnesis revealed 50 (96 %) cases of chronic bladder inflammation. Concurrent cancer was diagnosed in 6 (12 %) cases: 4 patients with urothelial carcinoma and 2 – with intestinal type adenocarcinoma. Follow-up of the remained 46 patients revealed the development of urothelial carcinoma in 1 patient which happened 6 months after his primary biopsy. By the way, this patient has already had upper urinary tract urothelial carcinoma in his anamnesis.

Conclusions. Study results show that there is a relatively frequent coexistence of cystic-glandular cystitis and bladder cancer. However, longterm follow-up of patients with cystic-glandular cystitis don’t allow us to consider this pathology as a preneoplastic.

Radical prostatectomy (RP) continues to be the «gold standard» in the treatment of localized prostate cancer (PC) for patients with a life expectancy of 10 years.

The purpose of this article is to review pertinent literature to the several surgical approaches for PC and compare both functional outcomes and oncological results of radical retropubic prostatectomy (RRP), laparoscopic radical prostatectomy (LRP) and robot-assisted radical prostatectomy (RARP). We chose and systematically reviewed 44 articles published between 1999 and 2013. Comparison analysis showed that the mean blood loss during RRP, LRP and RARP was 935, 442 and 191 ml respectively. Intraoperative transfusion required 19,9; 6,3 and 4,6 % patients respectively. We’d like to outline in our functional outcomes that within the 6-months and 12-months period of follow-up acute urinary retention experienced 89,1 and 92,7 % patients undergoing RARP.

However, lack of certain data and absence of standard assessment methods made objective evaluation of erectile function quite complex. Oncologic results revealed that positive surgical margin rates were higher for RARP in comparison to patients after RRP and LRP (the difference was statistically significant).

Nevertheless, the absence of randomized approach in an overwhelming majority of cases, as well as the short follow-up period are serious deterrents limiting the number of such trials. Therefore it’s still impossible today to draw certain conclusions about the superiority of any surgical approach for RP

Objective – assessing the predictive significance of clinical, histologic and biochemical factors for prediction of metastases in pelvic lymph nodes (MPLN), devising and validating of prognostic classification.

Materials and methods. The study enrolled 1140 patients subjected to radical prostatectomy (RPE) with standard pelvic lymphadenectomy for prostate adenocarcinoma: 865 of them at the classification devising stage and 275 in the course of validation.

Results. According to the findings of multivariate logistic regression analysis, PSA level, the tumor cT stage and Gleason score are independent predictors of MPLN detection after RPE (p < 0.05). The prognostic factors were stratified by score for assessing the detection of regional metastases after RPE, depending on the combination of predictors. In the group of patients with a score estimate of prognostic factors < 10, the MPLN detection rate was significantly lower than in the group of with a score estimate > 15, accounting for 3.5 % and 23.7 % respectively (р < 0.0001). In the course of validating the obtained findings in clinic, metastatic involvement of pelvic lymph nodes found in the result of RPE was diagnosed in 40.0 % of the patients with a score estimate > 15 and only in 1.3 % of those with a total estimate of prognostic factors < 10 (р < 0.0001).

Objective – to conduct pharmacoeconomic study of leuprolide acetate 45 mg once in 6 months (Eligard) for advanced prostate cancer from the perspective of Russian health care system

Materials and methods. Cost minimization analysis (CMA) and budget impact analysis (BIA) were performed. All calculations were made in the MS Excel model. CMA compared leuprolide acetate once in 6 months (Eligard 45 mg) with 7 other prolonged gonadotropin-releasing hormone (GnRH) analogs. BIA compared two scenarios: common practice consisting of 4 GnRH analogs; new practice that is leuprolide acetate once in 6 months in 20 % of patients. Costs of drugs, visits to oncologist and injections were calculated both in CMA and BIA. Time horizon was 5 years for CMA and 3 years for BIA. Number of patients treated with GnRH was defined taking into account 5 year survival rate. One-way sensitivity analysis was performed.

Results. Leuprolide acetate (Eligard) 45 mg is the most cost-saving option among all compared. Sensitivity analysis demonstrated that the results are sustainable if input parameters are varied in the range ± 25 % from baseline. Budget economy is expected when Eligard 45 mg is used in a part of patients population instead of other prolonged GnRH analogs.

Prostate cancer (PC) is the most common cancer among men. The risk of local recurrence of PC after radical prostatectomy (RP) remains significant. Multiparametric magnetic resonance imaging (mpMRI) is an effective method of local PC recurrence detection in the prostatic bed in patients after RP. Sensitivity of ultrasound examination and other radiological methods for detecting a small-sized relapse is very poor. Use of mpMRI in improving diagnostic accuracy in local relapse detection of PC after RP is of current importance, primarily in patients suitable for salvage radiation therapy.

Применение абиратерона ацетата (АА) сопровождается не только значимым увеличением выживаемости пациентов с метастатическим кастрационно-резистентным раком предстательной железы (мКРРПЖ), но также отдалением времени до развития рентгенологического прогрессирования заболевания. Эти преимущества относительно костных метастатических очагов могут быть связаны с непосредственным воздействием на метастатические клетки рака предстательной железы в костях или со специфическими механизмами, направленными на костное микроокружение. Чтобы проверить эти гипотезы, мы прове- ли исследование in vitro, направленное на оценку потенциального действия AA на первичные остеокласты (ОКЛ) / остеобласты (ОБЛ); in vivo оценивали изменения уровней маркеров костного метаболизма, С-концевых телопептидов коллагена 1-го типа (CTX, маркер костной резорбции) и щелочной фосфатазы (ЩФ) у 49 пациентов с мКРРПЖ, получавших AA.

Наши результаты показали, что AA оказывает статистически значимое ингибирующее действие на дифференцировку и активность ОКЛ, уменьшая экспрессию ОКЛ-маркерных генов TRAP (тартратрезистентная кислая фосфатаза), образование катепсина К и матриксной металлопротеиназы-9. Кроме того, AA способствовал дифференцировке ОБЛ и отложению костной матрицы, увеличивая экспрессию специфичных для ОБЛ генов RUNX2 (фактор транскрипции-2, содержащий домен Runt), образование ЩФ и остеокальцина. Также мы наблюдали in vivo значимое снижение уровня CTX в сыворотке и повышение уровня ЩФ у пациентов, получавших AA.

Эти данные позволяют предполагать новый биологический механизм действия AA, состоящий в прямом анаболическом и антирезорбтивном влиянии на костную ткань.

Seminal vesicle tumors are very rare malignancies which are not diagnosed in daily clinical oncology practice. Primary malignant tumors in seminal vesicle are difficult to define due to the lack of specific symptoms in the early stages of the disease. Another obstacle of proper diagnosis is the frequent invasion of tumors of the surrounding organs, especially the prostate, rectum and bladder which is difficult to differentiate. Very often seminal vesicle tumors are difficult to detect. Digital rectal examination as well as transrectal ultrasound scan (US) could reveal a bulky mass in the retrovesical space. Computed tomography and magnetic resonance imaging (MRI) are the main diagnostic methods which could help to reveal pathologic masses in the region of seminal vesicles. Levels of prostate-specific antigen, carcinoembryonic antigen and tumor markers specific for colorectal cancer are negative in seminal vesicle tumors.

The world experience of treating seminal vesicle tumors is very limited. There is paucity of data regarding appropriate choice of surgical approach and further treatment strategy and most of the time the treatment is individualized and based on very scarce information. At the same time surgical approach may vary significantly from vesiculectomy to pelvic exenteration. Possibility of using any regimens of adjuvant radiation therapy, chemotherapy or hormone therapy is highly debatable. However, aggressive surgical approach with radical tumor removal followed by extended lymphodissection shows the most favorable results in survival of patients suffering from seminal vesicle cancer.

Squamous cell carcinoma of the seminal vesicles is presumed to be an extremely rare disease as there are only 3 reports of it in the world literature. We report a case of patient B. suffering from squamous cell carcinoma of the right seminal vesicle whom we conducted an aggressive surgical approach – prostatovesiculectomy followed by resection of the posterior bladder wall. There was no adjuvant chemotherapy after surgery. In the next 22 months such diagnostic methods as US and MRI revealed no metastases or symptoms of the disease recurrence.

Ovarian cancer (OC) occupies the third place in the structure of gynecological malignancies and it’s still known for its high mortality rate. Therefore this disease remains one of the actual problems in modern oncology. The standard of care for patients with OC consists of primary surgery, followed by platinum-based chemotherapy in a case of the disease recurrence. These combined chemotherapy regimens allow to make significant improvement in survival rates in patients with OC. Surgery is another treatment option which can be applied in patients with recurrent OC including disease recurrence after prior chemotherapy. This method enables to make considerable improvement in survival for this certain group of patients.

We report a clinical case of young patient suffering from recurrent OC. The disease was initially diagnosed in 2001. After that the patient underwent several types of surgery and multiple courses of polychemotherapy. Detection of disease recurrence in 2013 required to conduct a very complicated surgical treatment. Currently this patient is under active follow-up with no signs of disease progression or disease recurrence. Application of enterocystoplasty technique (bladder augmentation using bowel segments) in reconstruction of the urinary tract in this particular case enabled to preserve the quality of patient’s life as well as to conduct radical surgery. In order to reduce artificial bladder activity, reduce/eliminate urinary incontinence and improve the quality of patient’s life botulinum toxin A was injected into the bladder wall. The effect of this injection was positive. To sum up, teamwork between the members of urology and oncology departments done in time allowed to provide complete urologic help which included examination with the use of modern highly technological equipment and treatment followed by methods of neurological rehabilitation. All these led to significant improvement of the quality of the patient’s life.

Transurethral resection of bladder is the standard surgical procedure for management of bladder cancer when it is suspected. Accurate clinical staging of the disease based on the histologic findings followed by further assessment of recurrence risks and risks of disease progression are vital for defining an optimal individualized treatment strategy. Early radical cystectomy (RC) is recommended for patients suffering from superficial bladder cancer at high risk for tumor recurrence.

Patients diagnosed with bladder tumors with multifocal lesions as well as with tumor size > 3 сm are related to a group of high risk for cancer progression. In this case in order to take a decision about the benefits of radical surgery, it’s essential to remember that RC is considered to be a major surgical procedure with a broad range of both intraoperative and postoperative complications. The vast majority of patients experience a lower quality of life based on the development of different types of metabolic alterations as well as the necessity for using urinals or inability to have adequate urination control. Organ-preserving therapy with active follow-up is thereby preferably to conduct on young patients with active life position.

In our clinical case we confirmed that such treatment strategy allows to establish adequate control over neoplastic process with less negative impact on patients’ quality of life.