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Cancer Urology

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Vol 19, No 2 (2023)
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EDITORIAL

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER

17-28 478
Abstract

Aim. To assess the correlation between clinical characteristics (sex, age, and maximum tumor size), 3D morphometric characteristics of renal lesions obtained through processing of multispiral computed tomography data, and renal tumor histology.

Materials and methods. Evaluation of kidney tumor malignancy on the basis of comparative analysis of primarily morphometric characteristics of the lesion obtained through processing of multispiral computed tomography data and histological tumor structure is presented. Data of 308 patients (175 (56.8 %) males and 133 (43.2 %) females) with unilateral renal tumors were analyzed.

Results. Multivariable analysis showed that malignancy of kidney tumor is associated with sex (male), location in the middle segment, tumor size, tumor shape (spherical with conical base) (24.8 %), while mushroom-like lesion shape was more common in benign tumors (35.2 %). In univariate models, only two variables were statistically significant predictors: patient sex and tumor shape.

Conclusion. The developed logistic model based on analysis of such predictors as sex and kidney tumor shape has a high percentage (87.6 %) of correct predictions of tumor histological structure.

DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER

41-46 597
Abstract

Background. A promising experimental approach to the personalized selection of treatment regimens is the study of the sensitivity of tumor cells to drugs in vitro on tumor organoids.
Aim. To generate a culture of prostate tumor organoids and to assess the effectiveness of the chemotherapeutic drug docetaxel used to treat prostate cancer on this culture.
Materials and methods. The initial tissue was dissociated using gentleMACS Octo homogenizer. Next, the cells were cultured in matrix Matrigel with addition of a serum-free complete nutrient medium. For histological analysis, organoids were fixed in a 10 % formalin solution, followed by staining with hematoxylin and eosin according to the standard protocol. Cell viability was assessed using MTS assay.
Results. In this work, we generated a new culture of prostate cancer cells. The histological analysis confirmed that the resulting organoids consist of tumor epithelial cells. As a result of the cytotoxic test, it was shown that in this case docetaxel (82.9 %; p = 0.32) didn’t reduce statistically significantly the viability of prostate cancer cells compared to the control.
Conclusion. The use of tumor organoids of prostate cancer for selection of an optimal treatment regimen is a promising experimental technology, however, further research is necessary for its introduction into practice.

47-55 298
Abstract

Background. The role of autophagy markers in prostate tumor recurrence has not been sufficiently investigated. We hypothesized that autophagy activation may be one mechanism by which prostate cancer cells survive exposure to high-intensity focused ultrasound (HIFU).
Aim. To compare tissue expression of autophagic LC3B marker in prostate biopsies before and after treatment of localized prostate cancer by HIFU ablation.
Materials and methods. 45 patients with localized morphologically confirmed prostate cancer were examined: group 1 – 25 patients of 65.6 ± 8.4 years without signs of recurrence or progression of the disease; group 2 – 20 patients of 67.5 ± 7.9 years with tumor recurrence proven during morphological examination. Immunohistochemical examination was performed by streptavidin-biotin method. In all cases, Anti-LC3B antibody ab48394 was used. The reaction results were quantified using the Histochemical score (Hs) system.
Results. Prior to treatment, all patients of group 1 showed moderate cytoplasmic expression (Hs = 111 [111; 115]) of antibodies against LC3B in prostate adenocarcinoma cells, 5 % of patients – weak cytoplasmic expression in muscle connective stromal cells (Hs = 47 [43; 50]), 10 % of patients – weak positive LC3B reaction in the vessel wall (Hs = 28 [20; 35]). After treatment, the expression of LC3B in adenocarcinoma cells became negative, in the cytoplasm of muscle connective stromal cells weak (Hs = 75 [67.5; 80.0]), in the endothelium of the vascular wall even weaker (Hs = 55 [45.5; 60.0]) (p <0.001). Prior to treatment in group 2, LC3B expression in tumor tissue was moderate in 89 % of patients (Hs = 151.5 [137.5; 160.0]), weak in muscle connective stromal cells in 12 % of patients (Hs = 44 [35; 51.5]), and weak in the vascular wall in 5 % of patients (Hs = 30 [25; 35]). After treatment, LC3B expression in adenocarcinoma cells became pronounced (Hs = 260 [250; 285]), in muscle connective stromal cells – moderate (Hs = 118 [100; 130]), in the vascular wall – weak (Hs = 45 [30; 55]) (p <0.001). There was a significant correlation between tumor recurrence and LC3B overexpression (r = 0.51; p <0.001).
Conclusion. The development of prostate cancer recurrence is associated with increased expression of autophagic LC3B protein. Increased LC3B expression, which is interpreted as evidence of autophagy activation and correlates with the risk of disease progression, is used by the tumor as an oncogenic advantage.

56-65 284
Abstract

Background. Prostate cancer is the 3rd most common diagnosis among malignant tumors. The first robot-assisted radical prostatectomy (RARP) was performed in 2001. Studies comparing RARP and radical retropubic prostatectomy (RRP) are limited. In Russia, the Da Vinci robot was first installed in 2007. At the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry the program of robot-assisted surgery started in November of 2008.
Aim. To perform first in Russia evaluation of 10-year functional treatment outcomes for patients with localized prostate cancer after RARP. To perform comparative analysis with RRP outcomes.
Materials and methods. Medical histories of 211 patients from the Urology Clinic of the A.I. Evdokimov Moscow State University of Medicine and Dentistry were analyzed. Among them, 62 patients did not satisfy the inclusion criteria. Therefore, the study included 149 patients who underwent surgical treatment for localized prostate cancer between January of 2009 and December of 2011. Depending on the technique of surgical intervention, patients were divided into 2 groups: 1st – RARP (n = 82), 2nd – RRP (n = 67). All RARP were performed by a single surgeon, RRP by 2 experienced surgeons (experience >1000 RRP).
Results. Median follow-up was 120 months in both groups. Overall survival in the 1st and 2nd groups was 85.4 and 86.6 %, respectively (p >0.05). For accuracy of functional outcomes analysis, patients who died during follow-up were excluded from the study. Frequency of neurovascular bundle preservation in the 1st and 2nd groups was 60.9 % (50/82) and 40.2 % (27/67), respectively (p = 0.01). Erectile function was preserved in 60.0 and 44.4 % males of the 1st and 2nd groups, respectively (p = 0.01). Age below 60 years (р = 0.009) and disease stage рТ2 (p = 0.026) were predictors of erectile function preservation after RARP. Continence frequency was 92.7 and 82.1 % in the 1st and 2nd groups, respectively (p = 0.048).
Conclusion. Ten-year comparative analysis shows that RARP allows to achieve significantly better parameters of urinary continence and erectile function preservation in men with localized prostate cancer than RRP.

66-74 856
Abstract

Aim. To compare clinical efficacy of salvage high dose-rate brachytherapy (HDR-BT) and external beam radiotherapy (EBR) in treatment of local recurrence of prostate cancer after radical prostatectomy (RP).
Materials and methods. Between January 2017 and December 2020, 60 patients with local recurrence of prostate cancer after RP were treated at the Russian Scientific Center of Roentgenology and Radiology. Two groups were identified: group 1 included 30 patients who underwent salvage external beam radiation therapy (EBRT) according to the classical fractionation regimen; in group 2, within the framework of the scientific protocol, 30 patients underwent 2 fractions of salvage HDR-BT with single boost dose of 15 Gy for total boost dose of 30 Gy. All patients in group 2 underwent pelvic multiparametric magnetic resonance imaging and positron emission tomography-computed tomography with prostatespecific membrane antigen ligands. In the 2nd group, transrectal biopsy of the prostate bed was also performed. Overall and biochemical recurrence-free survival, as well as the profile of early and late radiation complications, were analyzed.
Results. Mean age of the patients at the time of salvage radiation therapy was 67.5 years (95 % confidence interval 66.1–69). Median time before development of biochemical relapse after RP was 24 months (interquartile range 13–46 months). Median follow-up period for all patients was 45 months (interquartile range 36–63 months). There were no dropouts in this study. The overall survival rate was 100 % in both groups. Comparative analysis of prostate specific antigen (PSA)-specific recurrence-free survival showed a clear trend toward an increase in the brachytherapy group; however, with the number of observations, statistically significant differences could not be achieved (p = 0.075). Salvage EBRT is more toxic than salvage HDR-BT. Comparative assessment of radiation adverse effects revealed higher frequency of early genitourinary toxicity of grade I and intestinal toxicity of grades I and II in the salvage EBRT group than in the salvage brachytherapy group, as well as late gastrointestinal toxicity of grade I and II.
Conclusion. Salvage HDR-BT with 15 Gy × 2 fractions with total boost dose of up to 30 Gy was proved to be a promising treatment for local recurrence of prostate cancer after RP with an acceptable toxicity profile. There was also a trend towards increased PSA-specific recurrence-free survival in the salvage brachytherapy group compared with the salvage EBRT group.

75-88 401
Abstract

Background. In clinical practice, there is a need to predict clinical behavior of prostate cancer with germinal and somatic mutations in DNA homologous recombination repair (HRR) genes due to an atypical response to standard treatment methods. Also, the expediency of testing the mutational status of HRR genes is dictated by the possibility of using the PARP-inhibition strategy in metastatic castration-resistant prostate cancer (mCRPC). In addition to expanding the possibilities for targeted therapy the necessity to inform the relatives of mutation carriers is underestimated. It is also important to realize the fact of accumulation of somatic changes both in the primary tumor and in the metastatic lesion during tumor evolution and under treatment, which dictates the possibility of repeated biopsy with exhausted therapy possibilities.
Aim. Evaluation of prostate cancer clinical behavior features and response to drug therapy depending on the identified mutations in the HRR genes.
Materials and methods. The study was performed at the Clinical Oncological Dispensary No. 1 (Krasnodar). Clinical and morphological data of 27 patients with prostate cancer and identified germinal and somatic mutations in HRR genes (BRCA1, BRCA2, ATM, BARD, BRIP1, CDK12, CHEK1, CHEK2, PALB2, RAD51B, RAD51C, RAD54L, FANCL) were retrospectively analyzed. Statistical analysis was performed using the IBM SPSS Statistics v.22 statistical package.
Results and conclusion. The median age of patients was 61 years. The most frequent were mutations in the BRCA2 (37 %), CHEK2 (18.5 %), ATM (14.8 %) genes. More than half of the patients (69 %) had primary metastatic disease. The differentiation grade of G2 and G3 according to the classification of the International Society of Urological Pathologists (ISUP) with Gleason score of 7 (3 + 4) and 7 (4 + 3) were both detected in 27 % of cases. The type of mutation did not affect the time of castration resistance development (p = 0.216). The time to castration resistance increased close to statistical significance in the case of primary stage of T3–4N0M0 compared to other stages (log-rank p = 0.092). Progression-free survival (PFS) with docetaxel monochemotherapy was significantly longer when prescribed for metastatic hormone-sensitive prostate cancer with mutations in HRR genes compared to mCRPC (p = 0.061) and to primary metastatic disease (p = 0.04). At the same time, the risk of progression during therapy was higher for presence of regional lymph node metastases with primary advancement (p = 0.005; hazard ratio 1.167; 95 % confidence interval 2.765–267). There was also an advantage in PFS when prescribing docetaxel for BRCA1/2 and ATM mutations in comparison with other mutations (p = 0.038). When prescribing therapy with 2nd generation antiandrogens or abiraterone, progression-free survival is higher in the group of patients with prostate cancer with Gleason score of 7 (4 + 3) compared to cohort with other morphological types, and this difference is almost statistically significant (log-rank p = 0.091, Breslow p = 0.076, Taron-Ware p = 0.074). Targeted therapy with the PARP inhibitor Olaparib in the performed trial was received by 10 patients with HRR mutations. At the same time, according to the data of the PROfound trial, the advantage of Olaparib in radiological PFS was shown in germinal and somatic mutations in group A (BRCA1, BRCA2, ATM) and in the general group (A and B – other HRR mutations).

CLINICAL CASE

89-93 272
Abstract

Composite hemangioendothelioma is an extremely rare form of kidney tumor. The tumor mainly occurs in the extremities, head and neck; internal organs involvement is rarely reported. Patient, 61-year-old male, was admitted to the urology department for a left kidney tumor, which was found accidentally during an ultrasound examination. Magnetic resonance imaging showed an irregularly shaped tumor measuring 5.0 × 6.0 × 4.0 cm and located in the lower pole of the left kidney. The tumor was surgically removed with resection of the capsule of the kidney lower pole. Immunohistochemical study revealed diffuse bright expression of CD31 (clone JC70A), CD34 (clone QBEnd 10), ERG (clone ER111), FLI-1 (clone MRQ-1) in tumor cells. The index of proliferative activity Ki-67 (clone SP6) was 40 %. The morphological picture and immunophenotype of the tumor correspond to composite hemangioendothelioma of the retroperitoneal space. Magnetic resonance imaging of the retroperitoneal space on follow-up visit in 9 months visualized a tumor of the left kidney measuring 8.3 × 8.4 × 7.8 cm. Radical nephrectomy was performed. Pathology examination showed that tumor tissue was mainly represented by solid fields of the spindle cell component. In samples of the border between the tumor and fatty pararenal tissue, tumor invasion was observed up to the adjacent striated muscles, tumor growth into the tissue of the kidney gate was also found. Taking into account the morphological picture and the earlier immunohistochemical study, the removed tumor corresponds to composite hemangioendothelioma.
Composite hemangioendothelioma is a tumor of low malignant potential. It is extremely rare for this tumor to affect the kidney. At the same time, in the described case, the tumor was initially located in the retroperitoneal space, with involvement of the kidney capsule, and was assessed as a benign lesion. After 9 months, there was a recurrence of the tumor localized in the kidney with damage to the elements of the renal sinus, retroperitoneal tissue, and lumbar muscles. In this case, the tumor has significant malignant potential.

94-100 386
Abstract

In Russia, prostate cancer is a common disease with fast increasing incidence. In the vast majority of prostate cancer patients receiving hormone therapy, on average 18–36 months after the start of treatment refractoriness to androgen ablation develops. In 15–20 % of patients, signs of neuroendocrine differentiation may develop.
Neuroendocrine prostate cancer is an aggressive variant of castration-resistant prostate cancer with poor prognosis and low survival.
Due to the rarity of these types of tumors, specific diagnostic and treatment algorithms have not been developed. As a rule, they are similar to the methods for other malignant forms of prostate cancer and neuroendocrine tumors.

REVIEWS

101-110 419
Abstract

Background. Delineation of the prostate boundaries represents the initial step in understanding the state of the whole organ and is mainly manually performed, which takes a long time and directly depends on the experience of the radiologists. Automated prostate selection can be carried out by various approaches, including using artificial intelligence and its subdisciplines – machine and deep learning.
Aim. To reveal the most accurate deep learning-based methods for prostate segmentation on multiparametric magnetic resonance images.
Materials and methods. The search was conducted in July 2022 in the PubMed database with a special clinical query (((AI) OR (machine learning)) OR (deep learning)) AND (prostate) AND (MRI). The inclusion criteria were availability of the full article, publication date no more than five years prior to the time of the search, availability of a quantitative assessment of the reconstruction accuracy by the Dice similarity coefficient (DSC) calculation.
Results. The search returned 521 articles, but only 24 papers including descriptions of 33 different deep learning networks for prostate segmentation were selected for the final review. The median number of cases included for artificial intelligence training was 100 with a range from 25 to 365. The optimal DSC value threshold (0.9), in which automated segmentation is only slightly inferior to manual delineation, was achieved in 21 studies.
Conclusion. Despite significant achievements in the development of deep learning-based prostate segmentation algorithms, there are still problems and limitations that should be resolved before artificial intelligence can be implemented in clinical practice.

111-126 1234
Abstract

The implementation of innovative methods of drug therapy and biotherapy into clinical practice has significantly changed the treatment tactics for metastatic urothelial cancer. Currently, treatment regimens are successfully supplemented with immunotherapy (immune checkpoint inhibitors) or targeted therapy, and the effectiveness of such combinations can be quite high, but the optimal sequence of different types of drug therapy remains to be established. The development of correct algorithms using reliable biomarkers is necessary to select the correct sequence of prescribing drugs. Until now, the expression of programmed cell death-ligand 1 (PD-L1) and changes in fibroblast growth factor receptors 1–4 (FGFR1–4) have been the fundamental markers for choosing alternative treatment regimens for metastatic urothelial cancer. At the same time, the list of useful and sufficiently informative biomarkers is expanding, and therefore we tried to summarize the available data on the known biological markers for selection of treatment tactics for metastatic urothelial cancer.

EPIDEMIOLOGY OF UROLOGICAL ONCOLOGICAL DISEASES

127-132 262
Abstract

Background. In Russia, statistical record of multiple primary cancers has been implemented only recently, and there are few scientific publications. Multiple primary malignant neoplasms of the urologic locations are described even less in literature. The problem of multiple tumors becomes more pressing with each passing year.
Aim. To perform retrospective study of statistical data on urologic multiple primary cancer from one department.
Materials and methods. An analysis of retrospective data from medical histories of patients who received treatment between 1997 and 2020 in urologic oncology departments where the authors worked: Omsk Regional Oncological Dispensary (1997–2005), Moscow Oncology Clinical Hospital No. 1 (2003–2005), Moscow City Oncology Hospital No. 62 was performed.
Results. During the analyzed period, 23,299 hospitalizations including repeated were registered for 19,040 patients. Year-by-year data analysis showed 1,817 patients with multiple tumors, among them 1,508 patients with multiple primary malignant tumors, one and/or more of which were urologic pathology. The most common diseases were bladder cancer (n = 631), renal cancer (n = 618), prostate cancer (n = 614). A significant number of patients (n = 125; 8.29 %) had multiple tumors in 3 or more urologic locations. Tumors of the upper urinary tract were observed in 78 patients, testicle – in 36, penis – in 22, adrenal gland – in 10, urethra – in 4. Women comprised 28.05 % (n = 423) of the patients, men – almost 72 % (n = 1,085). This patient distribution by sex reflects the fact that urologic oncology includes both tumors of the urinary tract and male sex organs.
Conclusion. Currently, the questions of terminology of multiple primary tumors remain open: multiple primary, multilocular, bilateral tumors, and mixed tumors. There is a lack of understanding in definition of the border between implantation metastases and multiple primary tumors in upper tract urothelial carcinoma and bladder cancer, between metastatic or bilateral tumors in bilateral renal cell carcinoma of the same morphology, etc.

133-145 347
Abstract

Background. Bladder cancer is the most common malignancy of the urinary tract and one of the most common neoplasias in this group. The incidence and mortality rates of the population from bladder cancer differ significantly in different geographical regions of Russia.
Aim. To assess the main epidemiological indicators of malignant neoplasms of the bladder in residents of Saint Petersburg and the regions of Russia.
Materials and methods. The main epidemiological indicators of malignant bladder neoplasms in Saint Petersburg, Russia and individual federal districts for the period 2012–2021 were studied: crude and standardized rates of morbidity, mortality, prevalence, age structure of patients, the number of cases of diagnosis of the disease at various stages, indicators of one-year mortality and 5-year survival, data on completed cases of treatment of bladder neoplasms. Sources of information: Form No. 7 “Information on cases of malignant diseases” and the database of the Medical Information and Analytical Center (Saint Petersburg).
Results. During the period 2012–2021 in Russia, there was an increase in the incidence and prevalence of malignant neoplasms of the bladder. At the same time, mortality rates decreased, and 5-year survival rates increased. This fact indicates the effectiveness of the treatment of patients in this category. In more than 50 % of cases, the disease was detected at stage I of the pathological process, which is due to the proper level of diagnosis. The main medical and statistical indicators in patients with malignant bladder neoplasms in Saint Petersburg are comparable to the average Russian data, and in a number of parameters they exceed them.
Conclusion. Oncourological assistance to the population with malignant neoplasms of the bladder in Saint Petersburg is provided properly. The study of medical and statistical indicators in dynamics can be used to improve the algorithms of medical and diagnostic care for cancer patients.

TOPICAL PROBLEM

146-152 409
Abstract

Background. At the current stage of science and technology development, artificial intelligence (AI) is being actively developed and gradually introduced into the healthcare system.
Aim. To perform a literature review to assess the diagnostic value of AI in the detection of bladder cancer at the cystoscopy stage.
Materials and methods. We carried out a bibliographic search of articles in Medline and Embase databases using the keywords “artificial intelligence”, “cystoscopy”, “TURBT”.
Results. Automated image processing based on AI can improve the accuracy of cancer diagnosis during cystoscopy. According to the studies presented in the review, the sensitivity of AI system for the detection of bladder cancer via cystoscopy can reach 89.7–95.4 %, while its specificity is 87.8–98.6 %, which exceeds the diagnostic capabilities of standard cystoscopy in white light, the sensitivity and specificity of which, according to recent investigations, are approximately 60 and 70 %, respectively. Despite the promising results of these studies, modern science is currently at the stage of developing and evaluating the performance of various AI methods used to analyze cystoscopy images. To date, it would be premature to introduce and widely use these technologies in healthcare, since there are no prospective clinical studies to assess the effectiveness of AI systems in diagnostic cystoscopy and transurethral resection of bladder cancer.
Conclusion. Few studies show that AI-based cystoscopy is a promising approach to improvement of the quality of medical care for bladder cancer. Further research is needed to improve the diagnostic capabilities of AI and introduce the obtained technological data into clinical practice.



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