DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
Background. Laparoscopic and robot-assisted resection of the posterior kidney tumors can be performed through retroperitoneal and transperitoneal accesses. Supporters of retroperitoneal partial nephrectomy point to better results for neoplasms in this location. However, most surgeons use transperitoneal access.
Aim. To perform comparative analysis of the results of laparoscopic and robot-assisted partial resection of anterior and posterior renal neoplasms.
Materials and methods. The results of transperitoneal minimally invasive partial nephrectomy in 156 patients (86 (55.1 %) men and 70 (44.9 %) women) were analyzed. Anterior tumors (1st group) were diagnosed in 96 (61.5 %), posterior (2nd group) in 60 (38.5 %) patients. In the 1st group, mean tumor size was 3.4 ± 1.6 cm; in the 2nd group, 3.2 ± 1.4 cm. In the 1st group, laparoscopic partial nephrectomy was performed in 70 (72.9 %), robot-assisted in 26 (27.1 %) patients; in the 2nd group in 40 (66.7 %) and 20 (33.3 %) patients, respectively. Comparative analysis of operating time, warm ischemia time, complications and glomerular filtration rate was performed.
Results. No conversions into nephrectomy or open interventions were performed. Time of laparoscopic partial nephrectomy in the 1st group was shorter than in the 2nd: 108.6 min versus 120.5 min (р >0.05). In robot-assisted partial nephrectomy it was 90.5 and 112.6 min (р >0.05), respectively. For laparoscopic partial nephrectomy, mean warm ischemia time in the 1st group was 15.0 min, in the 2nd group it was 17.5 min (р >0.05); in robot-assisted operation it was 13.2 and 16.0 min (р >0.05), respectively. Blood loss volume was lower in the 1st group compared to the 2nd: 125 ml versus 230 ml (р <0.05). In all patients, renal cell carcinoma was diagnosed; Т1а tumors were predominant (in the 1st and 2nd group, 87.5 and 88.3 %, respectively; р >0.05). Postoperative complications in transperitoneal resection of anterior tumors were observed less frequently: 16.7 % versus 20.0 % (р >0.05). Grade I complications per the Clavien classification in the 1st and 2nd group were observed in 8 (8.3 %) and 6 (10.0 %) patients, grade II in 6 (6.3 %) and 5 (8.3 %) patients, grade III in 2 (2.1 %) and 1 (1.7 %) patients. After resection, urinary leakage through the drain was observed in 2 (2.1 %) patients of the 1st group and 1 (1.7 %) patient of the 2nd group; they underwent drainage of the upper urinary tract using a stent. Blood transfusion in the postoperative period was performed in 2 patients from each group (2.1 and 3.3 %, respectively). In the 1st group, glomerular filtration rate before and after surgery was 68 and 56 ml/min/1.73 m2, in the 2nd group 70.2 and 58.2 ml/min/1.73 m2, respectively; no significant difference was observed (р >0.05).
Conclusion. Transperitoneal access allows to safely perform minimally invasive resection of the anterior and posterior kidney tumors with results comparable to the perioperative results of retroperitoneal partial nephrectomy.
Background. The kidney cancer treatment remains cornerstone problem in our country for healthcare. Survival results of partial nephrectomy as a radical nephrectomy are similar in groups of patients with the same morphological features and was confirmed by previously results: “indications for nephron-sparing treatment of kidney cancer is determined with the degree of resectability, assessed subjectively by surgeon and his experience, ambitions and technical capabilities. It does not depend on oncological prognostic factors”. This thesis is actual due to oncological preoperative factors and limited only by tumor size. Therefore, development of technical capabilities, techniques and skills expand our capabilities in organ-preserving treatment.
Aim. To evaluate the effectiveness and safety of bipolar coagulation with fibrin glue in comparison with the standard technique of surgical suture to the area of non-ischemic partial nephrectomy.
Materials and methods. This is prospective trial which had included the results of treatment of 121 patients who received partial-nephrectomy for localized kidney cancer from 2015 to 2017 at the N.N. Petrov National Medical Research Center of Oncology. Two variants of hemostasis were used in the work: standard surgical (surgical suture) and electrohemostasis with an additional hemostatic component (fibrin glue). Among the selected patients, there were no patients with a single kidney and a pronounced violation of the excretory function of the organ.
Results. The groups were comparable in terms of tumor size (р = 0.09), morphometric characteristics according to the R.E.N.A.L. scale (p = 0.07), no differences were found in clinical and morphological staging. The use of electrohemostasis with a hemostatic glue component did not significantly affect at the excretory function of the kidney, assessed on the 3rd and 10th days after laparoscopic non-ischemic resection, which indirectly confirms the functional safety of the tested technique (р >0.05). The groups did not differ significantly in terms of the blood loss, hemotransfusions (р = 0.067), and none of delayed bleeding was found which indicates the reliability of electrohemostasis using an adhesive composition.
Conclusion. We proposed a patent “Method of surgical hemostasis in laparoscopic partial nephrectomy” RU2654402C1 by combining bipolar coagulation in the 90 W-effect 7–8 mode and hemostatic fibrin glue (SURGIFLO, PERCLOT). Used adhesive compositions complement the achieved electrohemostasis, and also provide sealing of the area of the resected kidney tissue.
Background. Radical removal of the tumor while maximizing sparing of the renal function are the main goals of the partial nephrectomy. Shortening of the warm ischemia time is one of the best ways to achieve good functional results of the surgery. Aim. To present our technique of non-ischemic laparoscopic kidney resection with preventive suturing around the tumor.
Materials and methods. Before tumor resection, sutures are placed around tumor spaced by 1 cm with moderate tension. Enucleoresection is performed between tumor and preplaced sutures in visually healthy plane. 30 patients underwent this technique.
Results. Median tumor size was 3.6 (1.5–7.2) cm. All patients had negative surgical margin. Warm ischemia was needed in 8 (26.7 %) patients with a median time of 9 minutes. Median operative time was 115 (65–185) minutes. There were no intra or postoperative complications. Trifecta was achieved in all patients (100 %).
Conclusion. This technique allows to perform the surgery in non-ischemic fashion, decrease bleeding and improve visualization of the resection field and achieve superior oncologic and functional results.
Background. Currently, treatment tactics for oligometastatic renal cancer are a debatable topic due to relatively localized process and high risk of skeletal-related events (SRE). Therefore, the effect of treatment on quality of life of these patients is an important subject.
Aim. To evaluate quality of life of patients with solitary renal cancer metastases in the bones before and after surgical treatment in combination with targeted therapy and without it.
Materials and methods. The study included 64 patients with solitary bone metastases and symptoms of SRE. The patients underwent surgical treatment due to solitary bone metastases of renal cancer in combination with targeted therapy (1st group; n = 25) and without targeted therapy (2nd group; n = 39). The effects of surgical treatment on patients’ condition were evaluated using the EORTC-QLQ-C30 questionnaire.
Results. In the 1st group, no statistically significant differences were shown for 8 of 30 indicators of the EORTC-QLQ-C30 questionnaire: restrictions in daily activities, dyspnea, appetite loss, nausea, vomiting, fatigue, tension, financial difficulties. The rest of the indicators showed statistically significant shift toward improvement. In the 2nd group, 7 of 30 indicators did not show statistically significant differences: restrictions in daily activities, dyspnea, sleep disorders, appetite loss, diarrhea, tension, financial difficulties. The rest of the questionnaire points also showed improvement (especially in decreased pain syndrome). In patients of the 2nd group before and after surgery, need for rest, fatigue, appetite loss and restrictions in performing work were more pronounced than in the 1st group. Additionally, after surgery patients of this group required more time in the chair and had more frequent diarrhea, while prior to surgery they complained more of nausea and fatigue. The last 2 parameters evaluating overall quality of life were higher in the 1st group before and after surgery which shows better baseline condition of these patients which was not affected by the treatment.
Conclusion. Therefore, surgical treatment of renal cancer bone metastases both in combination with targeted therapy and without it significantly improves quality of life according to the results of quality of life evaluation using the EORTC-QLQ-C30 questionnaire in patients of the studied groups.
Currently, combination immunotarget therapy is the treatment standard for patients with disseminated carcinoma of the renal parenchyma. Simultaneous inhibition of immune checkpoints of programmed cell death 1 (PD-1)/PD-L1 and VEGF/VEGFR signal transduction showed synergistic antitumor effect both in preclinical models and clinical practice.
The article presents the results of phase III CLEAR (NCT02811861) trial.
In the phase III CLEAR (NCT02811861) trial, 1069 patients with renal cell carcinoma with clear-cell component who previously did not receive systemic antitumor therapy were randomized 1:1:1 in groups of lenvatinib (20 mg/day per os) + pembrolizumab (200 mg intravenously once in 21 days), combination lenvatinib (18 mg/day per os) + everolimus (5 mg/day per os), and sunitinib (50 mg/day per os for 4 weeks with 2-week interval). The groups included 355, 357, and 357 patients respectively. Primary endpoint was progression-free survival (PFS) controlled by expertise of an independent central committee per the Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v.1.1). Additionally, patient overall survival (OS) and drug therapy tolerability were evaluated.
Median PFS for lenvatinib with pembrolizumab was significantly higher than for sunitinib (23.9 months vs. 9.2 months; progression hazard ratio (HR) 0.39; 95 % confidence interval (CI) 0.32–0.49; p <0.001). Similar advantage in PFS was observed for lenvatinib with everolimus compared to sunitinib (median PFS 14.7 months vs. 9.2 months; HR 0.65; 95 % CI 0.53–0.8; p <0.001). OS also was higher for lenvatinib and pembrolizumab combination compared to sunitinib (death HR 0.66; 95 % CI 0.49–0.88; p = 0.005). No advantages in OS of lenvatinib and everolimus compared to sunitinib were detected (death HR 1.15; 95 % CI 0.88–1.5; p = 0.3). Frequency of grade III and higher adverse events among patients receiving lenvatinib + pembrolizumab, lenvatinib + everolimus, and sunitinib were 82.4, 83.1, and 71.8 %, respectively.
Pembrolizumab + lenvatinib combination showed high effectiveness in 1st line treatment of renal cell carcinoma compared to sunitinib per PFS and OS values.
PROSTATE CANCER
Background. Prostate cancer is one of the most common malignant tumors in men. Tailored treatment approaches to metastatic castration-resistant prostate cancer based on identification of specific biomarkers have been introduced only recently. So far, the Food and Drug Administration has approved two drugs (olaparib and rucaparib) targeting the DNA repair genes.
Aim. To assess the frequency of mutations in the DNA repair genes in the Russian population.
Materials and methods. The article uses data from two centers (National Medical Research Radiological Center and A.I. Kryzhanovsky Krasnoyarsk Regional Clinical Oncological Dispensary) which included the largest numbers of patients in the largest Russian multicenter prospective trial ADAM. We performed genotyping of all valid tumor samples from 113 patients with metastatic castration-resistant prostate cancer to identify clinically significant mutations in the DNA repair genes.
Results. Next-generation sequencing demonstrated that 27 patients (23.9 %) had clinically significant mutations in DNA repair genes were, including ATM in 6 (5.3 %), BRCA1 in 5 (4.4 %), BRCA2 in 4 (3.5 %), CDK12 in 3 (2.6 %), CHEK2 in 2 (1.8 %), PALB2 in 2 (1.8 %), BRIP1 in 2 (1.8 %), BARD1 in 1 (0.9 %), RAD51B in 1 (0.9 %), and RAD51C in 1 patient (0.9 %).
Conclusion. Identification of mutations in the DNA repair genes should become a routine procedure, since a new treatment approach to metastatic castration-resistant prostate cancer is now being introduced.
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER
Background. Prostate cancer patients with a positive resection margin after radical prostatectomy are at risk of developing local recurrence. This risk should be carefully estimated in order to choose an optimal management strategy.
Aim. To develop a nomogram to predict the risk of local recurrence in patients with a positive resection margin using the data on patients who have undergone surgery.
Materials and methods. Routine pathomorphological examination of surgical specimens from 2255 patients with clinically significant local and locally advanced prostate cancer revealed 364 cases of positive resection margin. Statistical analysis allowed us to identify the most significant prognostic factors. Using selected preoperative factors and a mathematical model, we created a nomogram to predict local recurrence in patients with a positive resection margin.
Results. Our nomogram had an accuracy of 93% (area under the ROC curve (AUC) 0.9392; p <0.005), sensitivity of 0.99438, and specificity of 0.94545. The most significant prognostic factors included proportion of positive biopsy specimens, Gleason score (International Society of Urological Pathology (ISUP) grade estimated at routine pathomorphological examination), and presence and length of positive resection margin.
Conclusion. Our mathematical model and the nomogram based on it are highly accurate for predicting local recurrence and can therefore be used for choosing an optimal management strategy.
Background. Prostate cancer is amongst one of the most prevalent cancers in men worldwide. Combined hormonal-radiation therapy has become a standard of care for localized prostate cancer definitive treatment. As many as 30 % of men are at risk for disease progression within 10 years following radical treatment.
Aim. To assess the significance of prostate-specific antigen (PSA) density as a predictor of recurrence-free survival following combined hormonal-radiation therapy in patients with localized prostate cancer.
Materials and methods. We conducted a retrospective study of 272 patients with clinically localized prostate cancer treatment results who received combined hormonal-radiation therapy between January 1996 and December 2016.
Results. On the basis of our study, we confirmed high prognostic value of PSA density among patients with localized prostate cancer who received combined hormonal-radiation treatment. We utilized ROC-analysis in order to determine the threshold value of the PSA density index – 0.376 ng/ml/cm3, exceeding of which was associated with statistically significant reduction in the recurrence-free survival rate. The area under the curve was 0.711 (95 % confidence interval 0.653–0.764; p <0.0001). The risk of recurrence increased with rising of PSA density.
Conclusion. PSA density has proven to be a reliable tool for assessing the risk of prostate cancer recurrence among patients with localized prostate cancer who have undergone combined hormonal-radiation therapy.
Background. As of 2019, prostate cancer (PCa) is the second most common malignancy in men living in Russia (15.7 % of all cancer cases detected in 2019). Cardiovascular diseases, in particular atherosclerosis, are believed to be the second most frequent cause of death in PCa patients.
Aim. To evaluate cardiovascular safety of hormone therapy for PCa on the example of gonadotropin releasing hormone (GnRH) agonists and antagonists (leuprolide and degarelix), second-generation antiandrogens (enzalutamide), and steroidogenesis inhibitors (abiraterone).
Materials and methods. We analyzed the results of original studies assessing cardiovascular safety of hormone therapy in PCa patients published in 2020–2021 and indexed in PubMed. The results of other meta-analyses and systematic reviews were not included.
The search for publications was performed using the PubMed database and the Google system. The following key words were used for searching: prostate cancer, cardiovascular risks, cardiovascular safety, outcomes, atherosclerosis, etc. We analyzed studies published between January 2020 and January 2022. Articles in English and Russian were selected manually; no filters were applied.
Results. We examined the results of the latest and most relevant original studies assessing cardiovascular safety of key innovative hormone therapies for PCa. The majority of recent studies were based on routine clinical practice; they were registered in highly specialized cancer registers.
Hormone therapy is associated with cardiotoxicity, which increases the risk of non-cancer related death in PCa patients. New, sometimes conflicting evidence is being constantly accumulated. This evidence suggests that the GnRH antagonist (degarelix) has a better cardiovascular safety profile than the GnRH agonist (leuprolide); enzalutamide is safer than abiraterone. Further search for prognostic biomarkers in PCa patients is needed.
Conclusion. More high-quality studies analyzing adverse cardiovascular events in PCa patients conducted in routine clinical practice and registered in the online databases are the next stage to identify benefits of one antitumor drug over another. This will help to choose optimal hormone therapy algorithms for PCa patients and, therefore, increase their overall survival.
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
Background. Bladder cancer is the ninth most common malignant neoplasm worldwide. Hidden metastases at the time of diagnosis are the main reason muscle-invasive bladder cancer has poor prognosis. Even after radical cystectomy, muscleinvasive bladder cancer mostly progresses within 2 years with a recurrence rate of over 50 %. At stages II–IV of the disease, drug treatment is indicated before radical cystectomy. The main goal of neoadjuvant chemotherapy is to affect micrometastases, which may be present at the beginning of disease development. The response to ongoing chemotherapy can serve as a predictor of long-term survival.
Aim. To increase effectiveness of bladder cancer treatment.
Materials and methods. A total of 231 patients with bladder cancer were included in the study. The main contingent consisted of men over 60 years old with locally advanced tumors at stage Т2–Т4. Drug therapy was carried out in neoadjuvant mode before surgical treatment. Standard regimens were used: cisplatin + gemcitabine and MVAC (methotrexate, vinblastine, adriamycin, cisplatin). After four courses of neoadjuvant chemotherapy, the results were evaluated. With complete normalization of a patient’s condition, the issue of surgical treatment – radical cystectomy with one of the types of urinary diversion – was decided.
Results and conclusion. The follow-up period for patients after treatment was 62 months. In patients who underwent neoadjuvant chemotherapy, the median overall survival was 44.9 months, in patients without neoadjuvant treatment – 36.8 months with improvement in recurrence-free survival from 32.5 to 39.8 months (p = 0.08). Overall survival after neoadjuvant chemotherapy improved by 8.1 months (p = 0.09).
DIAGNOSIS AND TREATMENT OF URINARY TRACT TUMORS. CANCER OF THE URETHRA AND PENIS
Background. Penile cancer is a rare oncological pathology. Due to the intimate nature of the affected area and high significance of the organ for psycho-emotional state of the patient, at the early stages of the disease organ-sparing operations are preferred allowing to minimize the effect on patient’s quality of life without affecting oncological results.
Aim. To evaluate the effectiveness of treatment of early stages penile cancer using photodynamic therapy (PDT) with chlorin E6 derivatives.
Materials and methods. Between 2017 and 2021, PDT with chlorin E6 derivatives to treat early-stage penile cancer was performed in 15 patients between the ages of 29 and 84 years (mean age 56.4 years). Tumor stage was Tin situ–1bN0M0. PDT was performed with preliminary administration of Photolon and Photoran photosensitizers. Laser exposure on the tumor lesions was performed 3 hours after photosensitizer administration using laser device Latus-2 (662 nm), light dose 200–300 J/cm2, power density 0.21–0.41 mW/cm2.
Results. After 1 PDT session, full regression was observed in 11 (73.3 %) patients, partial regression in 4 (26.7 %) patients who underwent 2nd session 2 months later with full effect. Therefore, in all patients full regression of the tumors was achieved. Follow-up duration was 6–56 months. Recurrence was diagnosed in 1 (6.7 %) patient 36 months after PDT, 14 (93.3 %) patients are under observation without signs of local recurrence, among them for more than 4 years – 3 men, more than 3 years – 1, more than 2 years – 3, more than 1 year – 4 and more than 6 months – 3. During the follow-up, no regional or distant metastases were observed in any of the patients.
Conclusion. PDT with chlorin E6 derivatives is an effective organ-sparing treatment method for early-stage penile cancer with satisfactory oncological results without negative effect on patients’ quality of life. In 93.3 % of patients, local recurrence of the disease was not observed; during follow-up no distant metastases were diagnosed. It is necessary to point out satisfactory cosmetic results of the treatment: in all patients, elastic non-deforming scars were formed with full preservation of anatomical structures of the penis, no erectile dysfunction or disruption of urination were observed after PDT.
REVIEW
To compile this literature review, we studied at least 100 publications devoted to the genetic basis of clear cell, papillary, and chromophobic sporadic kidney cancer pathogenesis. Each of them considered the role of somatic gene and chromosomal mutations in the initiation, promotion, and tumor progression of sporadic renal cell carcinoma, emphasized the importance of determining the mutagenic profile of renal cell carcinoma for the future fate of patients.
CLINICAL NOTES
The use of 3D-computer technologies (3D-modeling, 3D-printing) in the surgical treatment of patients with kidney abnormalities contributes to a better understanding of anatomy at the preoperative planning stage and improves intraoperative navigation. We present a clinical observation using 3D-printing during performing organ-preserving laparoscopic surgery in a patient with localized formations of the horseshoe kidney parenchyma.
Diagnosis and treatment of upper tract urothelial carcinoma (UTUC) remain important problems of clinical urology. UTUC en bloc i.e. in one-piece removal during organ-sparing surgery is still hardly possible. The most typical endourological operations are either electrosurgery, holmium or thulium YAG laser tumor vaporization.
We present a clinical case of ureteroscopic en bloc UTUC removal using a new super pulse thulium fiber laser (SPTFL, FiberLase U3). Recent innovations and trends in this field are also discussed. The technical steps of en bloc ureteroscopic tumor removal allowing for diagnosis verification, identification of pT stage and surgical margin are described. The further innovations in laser UTUC removal include modulation of laser pulse length and development of the correlation between preoperative tumor characteristics and possibility of en bloc removal.
In clinical practice and scientific literature, there is very little data on the occurrence of tumors in the urinary intestinal reservoirs in patients after radical cystectomy with cystoplasty. A characteristic feature of such tumors is a long latent period before the formation of a relapse from 4 to 32 years.
The article describes a clinical case of a 1951 patient with a tumor of a small intestinal neocyst. From the patient’s history, there is a long-term hematuria (for 2 years) after radical cystectomy with ileocystoplasty. The intensity of hematuria increased to the formation of profuse with the development of severe anemia. During the examination according to magnetic resonance imaging, computed tomography, ultrasound and invasive diagnostic examinations, no tumor was detected. The patient underwent a diagnostic laparotomy, a tumor was found in the area of ureteral-reservoir anastomosis of the small intestine neocyst. Resection of the small intestine reservoir and ureteral transplantation was performed. The morphological picture of the removed tumor is urothelial cancer of moderate differentiation.
Secondary tumors of the small intestinal urinary reservoirs are rare and have the structure of adenocarcinoma. The mechanisms of their occurrence have not been fully studied at the moment. Dynamic monitoring of patients after radical cystectomy and ileocystoplasty should be carried out in a specialized center.
TOPICAL PROBLEM
Background. Prostate cancer incidence rates continue to increase every year, therefore, the study of the quality indicators for cancer care, especially during a pandemic, is of great importance.
Aim. To analyze prostate cancer incidence rates and quality indicators of cancer care in the Siberian Federal District.
Materials and methods. For the calculation of cancer incidence rates, population-bases cancer registry data were used. Quality indicators were calculated according to the methodological recommendations of P.A. Hertzen Moscow Oncology Research Institute – branch of the National Medical Research Radiological Center.
Results. The implementation of restrictive measures and the suspension of cancer screening programs in 2020 negatively affected the cancer care. The prostate cancer incidence rate decreased from 52.8 per 100 000 population in 2019 to 43.1 per 100 000 population in 2020, especially in the territories of the Republic of Tyva and the Omsk Region. Morphological verification in 2020 decreased compared to 2019 (97.0 % versus 97.8 %), with the exception of the Krasnoyarsk Territory and the Republic of Altai. Early prostate cancer detection increased from 62.9 to 64.0 %, and cancer detection at late stages decreased from 36.3 to 35.0 %. One-year mortality in the region decreased from 8.0 % (2019) to 7,3 % (2020), however, it increased significantly in the Republic of Tyva (from 3.2 to 40.0 %) and the Altai Republic (from 3.7 to 10.7 %). The number of patients who have been followed-up for 5 years or more increased from 40.7 to 42.3 %, except for Republic of Altai (from 32.8 to 25.0 %).
Conclusion. Delay in the diagnosis of prostate cancer is associated with advanced stage, poor survival and high cost treatment.
JUBILEE
ISSN 1996-1812 (Online)