DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
Background. High-grade non-muscle-invasive bladder cancer (NMIBC) is characterized by a high rate of recurrence, progression, and mortality associated with this disease. Organ-preserving treatment by transurethral resection and immunotherapy with bacillus Calmette-Guerin (BCG) is an initial approach to therapy in these patients. However, the efficacy of such therapy is limited. This justifies the use of other methods of treatment, such as TUR under the control of photodynamic diagnosis (PDD). Aim of this study was to evaluate the effectiveness of therapeutic interventions in patients with high-grade NMIBC.
Materials and methods. We have retrospectively analyzed results of follow-up of patients with primary or recurrent high-grade transitional cell NMIBC, treatment by TUR in conjunction with BCG or without it N.N. Alexandrov National Cancer Centre in the period from 2004 to 2013. In total, the study included 113 patients (27 women and 86 men), in the median age of 72 years. We have evaluated 5-year recurrence- and progression-free survival, analyzed an influence of prognostic factors and methods of treatment on the risk of recurrence and progression with Cox model and Kaplan–Meier method.
Results. With a median of follow up of 59 (12–116) months the rates of 5-year recurrence- and progression-free survival were respectively 42.5 and 71.6 %. Statistically significant association with the risk of recurrence was observed in multivariate Cox regression analysis for recurrent tumors (hazard ratio (HR) 2.73; 95 % confidence interval (CI) 1.61–4.62) and immunotherapy with BCG (HR 0.56; 95 % CI 0.31–0.99). BCG significantly increased recurrence-free survival in patients with both primary tumors, and with recurrent ones. Significant factors in the multivariate analysis with regard to the risk of progression were suspicion for muscle-invasive tumors according to the cystoscopic picture (HR 3.36; 95 % CI 1.09–10.4), abnormal tumor-free bladder mucosa, suspicious for carcinoma in situ (HR 7.23; 95 % CI 2.64–19.8), localization of tumor in the bladder neck, orifice zone, prostatic urethra (HR 2.91; 95 % CI 1.17–7.25) and PDD-assisted TUR (HR 0.10; 95 % CI 0.01–0.78). TUR under the control of photodynamic diagnosis significantly increased the survival to progression, regardless of the risk of progression, while BCG did not significantly affect the progression-free survival.
Conclusions. 6-week course of BCG therapy in patients with high-grade NMIBC significantly reduces the risk of recurrence and has no effect on the risk of tumor progression. PDD-assisted TUR provides a significant reduction in the risk of progression, but not recurrence. The findings justify the inclusion of both modalities in the treatment of high-grade NMIBC.
Postradiation obstructive changes of distal parts of the ureter most commonly occur after radiation therapy for cervical cancer, endometrial cancer, bladder cancer. Pathogenesis of postradiation lesions of the ureteral wall are explained by destructive effects of radiation on the basal membranes of the capillary cell, causing an occlusion, thrombosis, and neovascularization, which in turn leads to proliferation of fibroblasts and stromal fibrosis. Possible complications include hematuria, urinary tract infections, vesicoureteral reflux, stent migration, stent encrustation. By the way, presence of the stent is often associated with pain and discomfort in patients. Aim of this work is to improve the results of treatment of strictures of the lower ureter following radiotherapy, by evaluating effectiveness of extravesical uretherocystoanastomosis and Boari procedure.
Objective: to investigate the safety of vinflunine, the rate and duration of its treatment response, progression-free and overall survival rates in patients receiving this drug in routine clinical practice for first-line chemotherapy (CT) – resistant disseminated transitional cell carcinoma of the urinary tract.
Materials and methods. This retrospective observational multicenter study included data on 25 patients with verified disseminated transitional cell carcinoma of the urinary tract who took vinflunine for tumor progression after first-line CT performed in 11 Russian clinical centers in 23 March 2013 to 26 June 2016. The median age of the patients was 60 (44‒81) years. Their baseline somatic status was rated as ECOG 0 in 1 (4.0 %) patient, ECOG 1 in 13 (52.0 %) patients, EGOG 2 in 9 (36.0 %), and ECOG 3 in 2 (8.0 %). The most common sites of tumor foci were bones (n = 14, 56.0 %), lymph nodes of different groups (n = 14; 56.0 %), and lung (n = 9; 36.0 %).
Results. Adverse reactions were recorded in 24 (96.0 %) cases. The most common types of toxicity were asthenia (n = 19; 76.0 %), anemia (n = 18; 72.0 %), neutropenia (n = 13; 52 %), and nausea (n = 12; 48.0 %). Most adverse events were grades I–II and well controlled. There were no deaths due to adverse events. The best treatment response was regarded as partial in 6 (24.0 %) patients; stabilization and progression were observed in 10 (40.0 %) and 9 (36.0 %) patients, respectively. The median duration of partial response was 5.1 (95 % confidence interval (CI), 0.6–15.0) months; that of stabilization was 3.4 (95 % CI, 1.2–6.3) months. In all the 25 cases, the median progression-free and overall survival rates were 3.7 (95 % CI, 2.1‒5.3) and 6.5 (95 % CI, 5.2‒7.8) months, respectively. The somatic status was a predictor of overall survival (p < 0.0001).
Conclusion. The efficacy and safety of vinflunine in second-line therapy for first-line CT-resistant disseminated transitional cell carcinoma of the urinary tract in unselected patients agree with those previously observed in Phase III randomized trial.
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
Renal cancer (RC) is one of the most frequent diseases in oncological urology; the most common form of RC is the clear cell carcinoma. However, percentage of less-studied non-clear cell RC (nccRC) reaches up to 25 % of cases suggesting further studying, improvement of diagnosis and treatment of these tumors. The key events of carcinogenesis are genetic alterations including chromosomal aberrations and point mutations in proto-oncogenes and tumor suppressor genes. This review describes cytogenetic aberrations in the context of nccRC diversity according to the current ISUP classification. Translocation variants of nccRC (MiT-RC) were characterized separately as particular cases of the chromosome rearrangements involving MiT gene family (TFE3, TFEB, MITF). In addition, the main nccRC hereditary forms caused by germinal mutations in the genes FLCN, FH, and MET, as well as recent studies of sporadic tumors with using the next generation sequencing techniques were reviewed. These experiments were designed to search for somatic mutations throughout the tumor genome or exom and revealed the different mutational profiles of I/II papillary RC subtypes, chromophobe carcinoma versus oncocytoma. The review may be informative for oncologists, urologists, geneticists and specialists in related sciences.
Renal cell carcinoma (RCC) takes one of the leading places in the world incidence among malignant tumors of the genitourinary system. Metastatic renal cell cancer (mRCC) is detected in about 25–30 % of primary patients. 10 targeted immuno-oncology drugs for the treatment of mRCC were registered and approved for use from 2005 till the present time. Rapid growth of therapeutic options of mRCC treatment has created a problem for practicing oncologists and urologists as well as necessity to understand the principles and consistent optimization of targeted therapy to maximize the effectiveness of each treatment line. The article discusses issues of the correct choice of first-line targeted drugs, optimal dosing of sunitinib and aksitinib, alternative modes and alternating use of sunitinib, as well as the influence of objective response and hypertension, which developed on the background of the targeted therapy on the effectiveness of treatment.
Background. This article is a personal experience of a sequential targeted therapy of tyrosine kinase inhibitors for the period from June 2005 to July 2015.
Objective: evaluation of the results of the consistent application of targeted therapies in Moscow in this period.
Materials and methods. A retrospective analysis of cumulative progression-free survival in 220 patients of 354 patients with mRCC were studied. Was used Statistica 10.0 program.
Results. This article presents an analysis of the effectiveness of treatment and survival of patients receiving this therapy in cancer institutions Department of Health in Moscow.
Conclusion. Using of targeted therapy scheme sunitinib → sorafenib, we see no significant difference sVBP compared with scheme sorafenib → sunitinib with two lines ofsequential therapy tyrosine kinase inhibitors (16.9 and 18.2 months). According to our data total progression-free survival terms as applied to the 1st line of therapy tirosine kinase inhibitors (sunitinib and sorafenib), followed by the appointment pazopanib in the 2nd line (12.5 and 14.4 months) and pazopanib in 1st line followed by the appointment tirazinkinaz inhibitors (sunitinib and sorafenib) in the 2nd line (12.50 and 11.56 months) compared to the preliminary results of a multicenter randomized trial expected SWITCH II also not statistically different.
Background. The proportion of renal cell carcinoma (RCC) in the structure of oncological incidence in Russia is 3.9 %. This nosology has a leading position by the growth rate. The number of new cases of RCC from 2004 to 2014 increased by 42.9 %. Carbonic anhydrase (CA) enzymes are transmembrane enzymes that play an important role in pH regulation catalyzing reversible reactions of carbonic acid to carbon dioxide and water. Recently we have seen studies on prognostic and predictive value of CA9 expression in clear cell RCC.
Objective – reveal relationship between CA9 expression and proliferative activity, apoptosis, morphological picture and clinical course of a tumor.
Materials and methods. The study included 67 patients (47 men and 20 women) aged from 32 to 73 years (55.0 ± 7.6 years), suffering from clear cell RCC. All the patients were treated at the Medical Radiological Research Center. Follow-up period lasted from 8 to 116 months (mean – 36.5 months). Patients underwent nephrectomy, histological study with Fuhrman nuclear grading, immunohistochemistry with antibodies against p53, bcl-2, Ki-67 and CA9.
Results and conclusions. CA9 expression is associated with the expression of bcl-2, while the lack of CA9 expression is associated with p53. Loss of CA9 expression is a poor prognostic factor and it is associated with the development of metastasis and recurrence of the disease, as well as lower disease-free survival.
While analyzing data from domestic and foreign literature, we looked at various molecular factors of kidney tumors, some of which may be considered as diagnostic and prognostic markers of the clinical course of the cancer process. Here presented also is an assessment of the possible use of these indicators, in conjunction with other classic factors, in the prognosis of survival and the evaluation of the risk of metastasis in renal cancer.
Renal cancer is one of the most rapidly spreading diseases in the world. As you know, a few years ago, overall survival of patients with metastatic renal cell carcinoma (mRCC) was disappointing: median overall survival rarely exceeded 13 months, while 5-year survival rate was less than 5 %. Immunotherapy with interferon-alpha and interleukins demonstrated low efficiency. Appearance of targeted therapies for the treatment of mRCC significantly increased the duration and quality of life of patients receiving drug treatment. Nowadays due to this methodology and guided by the results of randomized clinical trials we can choose an optimal sequence of therapy and control the disease in three consecutive lines for about 30 months. In this article we would like to share an experience of the use of targeted therapies in the Saint Petersburg City Clinical Oncology Dispensary in patients with clear-cell mRCC.
PROSTATE CANCER
This article presents the data on the state of oncological care in patients with cancer, particularly prostate cancer in some countries of Central Asia – Republic of Uzbekistan, Kazakhstan and Kyrgyzstan. We have listed data on detectability during preventive examinations, morbidity, mortality, morphological verification, 1-year mortality, structure, distribution by stages, dispensary groups in patients with prostate cancer in these countries.
Prostate cancer (PC) is an actual problem of modern oncourology due to the continuing high rates of this disease morbidity and mortality. Despite improvements in diagnostic techniques, incidence of common forms of the disease remain to be high. Metastatic castrate-resistant prostate cancer (mCRPC) is a disease with an extremely poor prognosis, in which standard methods of hormonal treatment are ineffective. Heterogeneity of CRPC patient population requires differentiated approach to the administration of therapy based on the availability of various prognostic factors. Not so long ago chemotherapy with docetaxel was the main treatment for this group of patients. Second-line hormonal therapy was introduced into clinical practice in 2011 with the advent of new drugs aimed at the complete suppression of testosterone production. Enzalutamid, a new drug for second-line hormonal therapy, has essentially different mechanism of action. It is able to block androgen receptors selectively and disrupt translocation of the signal from the receptor into the cell and into the cell nucleus. Large randomized trials that studied the effectiveness of this drug allowed to register it for clinical use, including our country. An article presents a review of the literature on clinical trials devoted to the use of a drug in CRPC patients.
Castrate-resistant prostate cancer (CRPC) is one of the most complex and currently completely unsolved problems of oncourology. Possible novel treatment of CRPC is administration of Octreotide Long, long-acting somatostatin analogue.
In this paper we have shown an experience of treatment with Octreotide Long 30 mg and dexamethasone in 69 CRPC patients from February 2014 to March 2016. We have assessed an efficacy and safety of the therapy. Age of patients ranged from 56 to 89 years, all patients had continued androgen deprivation. Response to the treatment was assessed clinically by the following factors: change in the level of prostate specific antigen (PSA) in serum, dynamics of indicators of general and biochemical blood tests, the level of pain syndrome and improvement in the patient’s quality of life. Total response to reduction and stabilization of PSA level was achieved in 70.9 % of patients. In general, the best results were observed in the group of patients treated with Octreotide Long before first-line chemotherapy with docetaxel. Tolerability of Octreotide Long in combination with dexamethasone in all cases was good. No significant side effects – neither hematological, nor clinical were noted. We also did not register any cases of drug discontinuation due to its intolerance.
CONGRESSES AND CONFERENCES
Resolution on the results of the Meeting of Experts on the treatment of castrate-resistant prostate cancer.
CLINICAL CASE
Paraganglioma is hormonally active tumor originating from chromaffin tissue of sympathoadrenal system that secrete large amounts of catecholamines. Paraganglioma of the urinary bladder is a rare neoplasm, constituting approximately 0.06 % of all tumors of this localization. It is believed that this disease arises from embryonic remnants of chromaffin cells in the sympathetic plexus of the detrusor. Up to 10 % of these tumors have malignant origin. Diagnosis and tactics of treatment of patients with malignant paragangliomas of the bladder presents certain difficulties. The article describes 2 clinical observations of patients with this bladder pathology.
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