DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. RENAL CANCER
Background. Modern imaging methods make it possible to detect kidney tumors at early stages which, along with active development of laparoscopic technologies, has led to an increase in the number of nephron-sparing surgeries and their effectiveness. The RENAL, PADUA, C-index, ZONAL NePhRO, and SPARE nephrometry score systems are actively used to predict outcomes of partial nephrectomy.
Aim. To evaluate the effectiveness of nephrometry scores in predicting the results of minimally invasive partial nephrectomy.
Materials and methods. The data on 90 patients who underwent laparoscopic or robotic partial nephrectomy at the Urology Center of the Mariinsky Hospital from September 2021 to May 2023 were retrospectively evaluated. There were 43 men (47.8 %) and 47 women (52.2 %). The median age of patients was 61 years (interquartile range (IQR) 48–69). Tumor of the left kidney was diagnosed in 46 (51.1 %) patients, and tumor of the right kidney in 44 (48.9 %) patients.
Results. Mean operative time was 132 ± 39 minutes. Median warm ischemia time and intraoperative blood loss were 15 minutes (IQR 12–20 min) and 150 mL (IQR 70–257.5), respectively. Mean hemoglobin level and red blood cell count before surgery were 132 ± 15 g/L and 4.6 ± 0.63 × 1012/L, respectively. After the surgery, the mean values were 119 ± 16 g/L and 4.06 ± 0.6 × 1012/L, respectively. Median creatinine and mean glomerular filtration rate before surgery were 83.5 µmol/L (IQR 72–97 µmol/L) and 76.9 ± 21 mL/min, respectively; in the early postoperative period, 83 µmol/L (IQR 70–100 µmol/L) and 76.4 ± 24 mL/min, respectively. The strongest relationship was established between the RENAL and PADUA scores (r = 0.907; p <0.001), a slightly weaker relationship was found for the PADUA and SPARE scores, as well as PADUA and C-index (r = 0.856; p <0.001 and r = –0.785; p <0.001, respectively). The RENAL score showed high predictive value in assessing the volume of intraoperative blood loss and operative time (r = 0.881; p = 0.001 and r = 0.854; p <0.001, respectively). The PADUA scale demonstrated high predictive efficiency for warm ischemia time (r = 0.775; p = 0.001). C-index significantly predicted the volume of intraoperative blood loss and operative time (r = –0.807; p <0.001 and r = –0.797; p = 0.001, respectively).
Conclusion. All of the above nephrometry scores showed high predictive efficiency, but the RENAL and PADUA scores were the most valuable.
Introduction. The phase 3 CLEAR study demonstrated that lenvatinib plus pembrolizumab significantly improved efficacy versus sunitinib as first-line treatment for patients with advanced renal cell carcinoma (RCC). Prognostic features including presence and/or site of baseline metastases, prior nephrectomy, and sarcomatoid features have been associated with disease and treatment success. This subsequent analysis explores outcomes in patients with or without specific prognostic features.
Methods. In CLEAR, patients with clear cell RCC were randomly assigned (1:1:1) to receive either lenvatinib (20 mg/day) plus pembrolizumab (200 mg every 3 weeks), lenvatinib (18 mg/day) plus everolimus (5 mg/day), or sunitinib alone (50 mg/day, 4 weeks on, 2 weeks off). In this report, progression-free survival, overall survival, and objective response rate were all assessed in the lenvatinib-plus-pembrolizumab and the sunitinib arms, based on baseline features: lung metastases, bone metastases, liver metastases, prior nephrectomy, and sarcomatoid histology.
Results. In all the assessed subgroups, median progression-free survival was longer with lenvatinib plus-pembrolizumab than with sunitinib treatment, notably among patients with baseline bone metastases (hazard ratio (HR) 0.33; 95 % confidence interval (CI) 0.21–0.52) and patients with sarcomatoid features (HR 0.39; 95 % CI 0.18–0.84). Median overall survival favored lenvatinib plus pembrolizumab over sunitinib irrespective of metastatic lesions at baseline, prior nephrectomy, and sarcomatoid features. Of interest, among patients with baseline bone metastases the HR for survival was 0.50 (95 % CI 0.30–0.83) and among patients with sarcomatoid features the HR for survival was 0.91 (95 % CI 0.32–2.58); though for many groups, median overall survival was not reached. Objective response rate also favored lenvatinib plus pembrolizumab over sunitinib across all subgroups; similarly, complete responses also followed this pattern.
Conclusion. Efficacy outcomes improved following treatment with lenvatinib-plus-pembrolizumab versus sunitinib in patients with RCC – irrespective of the presence or absence of baseline lung metastases, baseline bone metastases, baseline liver metastases, prior nephrectomy, or sarcomatoid features. These findings corroborate those of the primary CLEAR study analysis in the overall population and support lenvatinib plus pembrolizumab as a standard of care in 1L treatment for patients with advanced RCC.
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. PROSTATE CANCER
Background. Limited sensitivity and specificity of existing prostate cancer (PCa) diagnosis methods drive the search for new markers. A number of studies has demonstrated the potential for measuring expression of certain microRNAs in urine.
Aim. To evaluate the diagnostic potential of measuring microRNA expression in urine in PCa.
Materials and methods. A collection of urine sediment samples from 19 patients with benign prostatic hyperplasia and 44 patients with PCa was analyzed. RNA was isolated using the miRNEasy Serum/Plasma Kit. 16 µL of RNA isolated from each sample were converted into cDNA, which served as a template for real-time polymerase chain reaction. For sequencing, microRNA libraries were prepared using MGIEasy Small RNA Library Prep Kit v.2.0. The formed DNA nanoballs were placed into an MGI DNBSEQ-G400 sequencer. Sequencing results were processed using IsoMiRmap. Differences in microRNA abundance were analyzed using DESeq2. For miRNA-21, high-throughput sequencing data were corroborated by the results of quantitative real-time polymerase chain reaction.
Results. 1154 types of microRNA were identified, 11 were differentially represented in all comparison groups. The most significant differences in cell sediment between benign prostatic hyperplasia and PCa patients were recorded for miR-451a (area under the curve (AUC) 0.98). Additionally, the abundance levels of two microRNA isoforms were significantly different: hsa-miR-144-3p|-1 (AUC 0.96) and hsa-miR-21-5p|+4 (AUC 0.68).
Сonclusion. This study confirms that altered expression of microRNAs miR-21, miR-451a and miR-144-3p is associated with PCa, can be detected in urine samples, and can also be a potential non-invasive diagnostic criterion.
Background. Analyzing the sensitivity of patient-derived tumor organoids to anti-cancer medications shows great potential for tailoring personalized treatment plans.
Aim. To obtain two prostate tumor organoid cultures, optimize the composition of culture medium, and to evaluate
the efficacy of the chemotherapeutic drug docetaxel using the obtained organoid cultures.
Materials and methods. The initial tissue was dissociated using the gentleMACS Octo homogenizer. The obtained cells were cultured in Matrigel with different culture media for selection of the optimal one. Cell viability and growth rates were assessed using the MTS assay.
Results. In this study, we successfully obtained two organoid cultures of prostate cancer cells and identified the most effective composition of culture medium. Using a cytotoxic test, it was shown that the obtained organoid cultures of prostate cancer cells had different sensitivity to docetaxel which was reflected in different inhibition of the tumor cell growth rate.
Conclusion. The utilization of prostate cancer organoids to determine the best treatment approach is a highly promising experimental technology. Nevertheless, additional research is required before integration of this technology into clinical practice.
Background. Despite improved surgical techniques in treatment of prostate cancer, biochemical recurrence after surgery (increase in prostate-specific antigen level (PSA) by 0.2 mg/mL or higher in 2 consecutive measurements) develops in 20–40 % of patients depending on disease stage and tumor aggressiveness. To diagnose the source of biochemical recurrence, patients undergo positron emission tomography/computed tomography (PET/CT) with 18F- or 68Ga-labeled prostate-specific membrane antigen (PSMA). Both tracers showed comparable results in phase III trials with positive prognostic values between 84 and 92 % at PSA level ≥1 ng/mL. A number of articles has been published demonstrating the effectiveness of salvage lymph node dissection (SLND) after local treatment of carefully selected patients in the long-term. According to the results of these publications, drug therapy in patients with oligometastatic progression can be delayed by years and potentially increse overall survival.
Aim. To analyze the literature and our own experience of SLND in treatment of nodal oligorecurrent prostate cancer.
Materials and methods. At the Clinic of the Moscow City Oncological Hospital No. 62 between 2012 and 2023 in the frame-work of the clinical protocol, 32 patients with nodal oligorecurrent prostate cancer underwent SLND after radical prostatectomy: 12.5 % (4 of 32) of patients through open access, 87.5 % (28 of 32) through laparoscopic access.
Results. Two groups were identified: 1st group (n = 20) of patients without androgen deprivation therapy (ADT) and/or external beam radiotherapy after SLND; 2nd group (n = 12) of patients receiving immediate ADT and/or external beam radiotherapy after SLND.
In the 1st group, an additional criterion of SLND effectiveness was introduced, namely, PSA response: complete, partial PSA response, or its absence. In patients with partial PSA response (n = 4), its depth was evaluated; it varied between 16 and 83 %. PSA response depth did not correlate with duration of response.
Complete PSA response was achieved in 60 % (n = 12) of patients. Duration of response varied between 3 and 133 months without additional treatment.
In the 1st group, median follow-up was 6 months and progression-free survival was 18 months; in the 2nd group, median follow-up was 31 months and median progression-free survival was 41.9 months (p = 0.84456).
Conclusion. The standard of treatment for patients with metastatic hormone-sensitive prostate cancer is ADT in combination with 2nd generation antiandrogens. Improvement and availability of PET/CT with PSMA allowed to identify patients with nodal oligorecurrent prostate cancer in which SLND without ADT allows to achieve complete PSA response in 60 % of cases and delay ADT associated with a number of adverse events. SLND is characterized by low number of postoperative complications, short hospital stay.
Background. Hypofractionated radiation therapy is a standard radical approach for treatment of patients with localized prostate cancer of low and intermediate risk. Clinical practice of applying this approach in patients with high and very high risk of progression has not been established.
Aim: improving the effectiveness of hormonal/radiation therapy in patients with high and very high risk prostate cancer using an original radiotherapy technique.
Materials and methods. In 2012, a new technique of hypofractionated radiation therapy based on simultaneous integrated boost aimed at the prostate, seminal vesicles, and regional lymph nodes was developed at the Radiotherapy Department of the N.N. Blokhin National Medical Research Center of Oncology. The phase II single-center prospective cohort trial included 40 patients with high and very high risk prostate cancer who received combination hormonal/ radiation therapy between 2012 and 2018. Median follow-up was 96 (61–124) months.
Results. None of the patients had grade III–IV adverse events (according to the RTOG/EORTC scale) in the distal parts of the gastrointestinal tract and urogenital system. Five-year biochemical and local controls were 80 % and 100 %, respectively.
Conclusion. The results of this study show that the developed hypofractionated radiation therapy technique is safe with 5-year biochemical control outcomes matching reported in the literature. However, to determine true clinical significance of the technique, initiation of a randomized phase III trial is required.
Over the past few years, the use of spacers to optimize radiation treatment of prostate cancer has become increasingly popular in radiotherapy practice. In Russia, the experience of clinical application of this technology is small and limited to few trials at federal centers. The technique of perineal implantation of a biodegradable spacer is invasive and requires the participation of specialists with appropriate manual skills. Therefore, informing urologists, urologic oncologists, and interventional radiologists on the methodological aspects of this procedure has significant practical importance.
The purpose of this work is to describe the methodology of using a new Russian medical device as a biodegradable spacer – a monophasic implantable gel (hydrogel) based on stabilized (cross-linked) hyaluronic acid of non-animal origin (EsteFILL intim), which makes it possible to reduce radiation exposure to the anterior wall of the rectum and has other positive effects (increased accuracy of radiation delivery, reduced risks of radiation-induced erectile dysfunction) in different radiotherapy methods of prostate cancer treatment. The described procedure was developed and approved at the Department of Radiotherapy of the N.N. Petrov National Medical Research Center of Oncology. The design of the study implying implantation of the stabilized non-animal hyaluronic acid (EsteFILL intim) was approved by the local ethics committee (protocol No. 16 dated 21.09.2023) and approved as a promising research work at the meetings of the Problem Commission (protocol No. 125 dated 25.09.2023) and the Academic Council of the N.N. Petrov National Medical Research Center of Oncology (protocol No. 8 dated 26.09.2023).
Background. Whether disease burden in patients with metastatic castration-sensitive prostate cancer (mCSPC) predicts treatment outcomes is unknown. We assessed apalutamide treatment effect in TITAN patients with mCSPC by disease volume, metastasis number and timing of metastasis presentation.
Methods. These protocol-defined and post hoc analyses of the phase III randomised TITAN study evaluated clinical outcomes in patients receiving 240 mg/day apalutamide (n = 525) or placebo (n = 527) plus androgen-deprivation therapy (ADT). Subgroups were defined by volume (high: visceral and ≥1 bone metastases or ≥4 bone lesions with ≥1 beyond vertebral column/pelvis), development of metastases per conventional imaging (synchronous: at initial diagnosis; meta-chronous: after localised disease) and oligometastases (≤5 bone-only metastases) or polymetastases (>5 in bone ± other locations or ≤5 in bone plus other locations). Overall survival (OS), radiographic or second progression-free survival, and time to prostate-specific antigen progression or castration resistance were assessed using Cox proportional hazards models.
Results. Of 1052 patients, 63 %, 81 %, 54 %, 27 %, 5.7 %, and 8.0 % had high-volume, synchronous, synchronous/high-volume, synchronous/low-volume, metachronous/high-volume, and metachronous/low-volume disease, respectively. The OS benefit favoured apalutamide plus ADT versus ADT alone in synchronous/high-volume (hazard ratio (HR) 0.68; 95 % confidence interval (CI) 0.53–0.87; p = 0.002), synchronous/low-volume (HR 0.65; 95 % CI 0.40–1.05; p = 0.08), metachronous/high-volume (HR 0.69; 95 % CI 0.33–1.44; p = 0.32) and metachronous/low-volume (HR 0.22; 95 % CI 0.09–0.55; p = 0.001) subgroups. Apalutamide improved other clinical outcomes regardless of subgroup, with similar safety profiles. Most favourable outcomes were observed in oligometastatic disease.
Conclusion. TITAN patients derived a robust benefit with apalutamide plus ADT regardless of disease volume and timing of metastasis presentation without differences in safety, supporting early apalutamide intensification in mCSPC.
DIAGNOSIS AND TREATMENT OF URINARY SYSTEM TUMORS. URINARY BLADDER CANCER
Context. Increased bladder cancer prevalence among farm owners and farm workers has been linked to high use of phytosanitary agents in agricultural activities. These results suggested that exposure to phytosanitary products and the risk of bladder cancer may be related.
Objective. Examining the connection between phytosanitary products and the risk of bladder cancer was the goal of the current systematic review and meta-analysis.
Methods. Through PubMed, Scopus, Science Direct, and Web of Science, a thorough literature searches of works updated to 2022 was carried out. The estimates of odd ratio (OR) with 95 % confidence intervals for the highest versus the lowest exposure to pesticide were compiled using fixed- or random-effect models. A prevalence meta-analysis was performed using Cochrane Revman Software.
Results. According to the pooled OR estimates, exposure to phytosanitary conditions was linked to a higher risk of bladder cancer (OR 1.59; 95 % confidence interval 0.51–5.02). Results in the cohort and case–control groups both showed a connection.
Conclusion. According to the majority of studies, exposure to phytosanitary agents and the risk of bladder cancer are directly correlated. According to certain research, smoking may increase the risk of bladder cancer.
CLINICAL NOTES
Currently, the main approach to treatment of malignant tumors of the renal pelvis is radical nephroureterectomy. In some patient categories, organ-sparing surgeries are possible if several criteria are met. According to scientific publications, tumor recurrence and progression rates significantly vary in non-radical surgical treatment, and outcomes are contradictory. The article presents a clinical case of organ-sparing treatment of a young patient with progressive urothelial carcinoma.
Serous tumors are rare in the group of non-germ cell testicular tumors, ad are morphologically similar to serous ovarian tumors. Preoperative diagnosis of this tumor is difficult due to the lack of specific signs according to clinical and instrumental research methods. In turn, histological verification of a serous borderline tumor is also a difficult task and requires differential diagnosis, primarily with serous cystadenocarcinoma, which, unlike a serous borderline tumor, can metastasize and is generally characterized by worse prognosis. Immunohistochemical examination allows to exclude other tumors with a similar morphological structure, including mesothelial tumors. Due to the rare occurrence of testicular serous tumors, there is minimal clinical experience in the treatment of these tumors worldwide, and there is still no consensus on guidelines for their treatment. Radical orchiectomy is recommended for patients with border-line serous tumors.
This article presents a clinical case of a testicular serous borderline papillary tumor with a discussion of the literature data on the instrumental, morphological, and immunohistochemical characteristics of this rare tumor in men.
Undifferentiated pleomorphic prostate sarcoma is an extremely rare neoplasm. In the available literature, less than 50 clinical cases were described. Usually, the clinical manifestation of the disease is nonspecific and is primarily associated with bladder outlet obstruction. Additionally, most patients have normal levels of prostate-specific antigen, while ultrasound and MRI can visualize irregularly shaped lesions, often extending beyond the prostate gland. Diagnosis requires exclusion of other signs of specific differentiation, apart from fibroblastic and myofibroblastic. There is no established treatment plan for patients with pleomorphic prostate sarcoma due to extreme rarity of the disease. For localized forms of the disease, radical laparoscopic prostatectomy is often used, but more aggressive treatment options are also being considered, including total pelvic exenteration, chemotherapy and radiation therapy. However, in most cases metastasis is revealed after primary treatment. Regional metastases are often localized in the rectum, bladder, in the area of previous surgery, and regional lymph nodes, while distant metastases are found in the lungs, liver, bones and distant lymph nodes, thereby indicating aggressive progression and poor prognosis of the disease.
In this article, we present our own clinical observation of a patient with confirmed undifferentiated pleomorphic prostate sarcoma.
Among surgical methods of treatment of male stress urinary incontinence, implantation of an artificial urinary sphincter is the leading technique. Despite its acceptable effectiveness, the intervention carries a risk of complications, some of which require removal of a component or the entire device.
The article presents a clinical case of primary artificial urinary sphincter cuff placement and literature review on this topic.
Urachal carcinoma is a rare pathology of the lower urinary tract. In a review of the largest case series, five-year overall survival was about 50 %. The poor prognosis is mainly attributed to advanced stage of the disease due to relative absence of symptoms in localized disease, the difficulty of identification by cystoscopy, and the lack of clear consensus regarding investigation and treatment of localized and advanced disease.
We report a case of treatment of a 46-year-old patient with primary urachal carcinoma. Cystoscopy revealed a lesion on the bladder closer to the apex. Magnetic resonance imaging of the pelvic organs revealed a picture of a malignant neoplasm of the bladder with growth into the paravesical tissue and the anterior wall of the bladder. The patient underwent surgery followed by adjuvant chemotherapy.
REVIEWS
The article is dedicated to the modern methods of diagnosis and treatment of oligometastatic prostate cancer based on a large amount of literature data. The main goal of metastasis-directed therapy in oligometastatic prostate cancer is slowing of metastatic process, increased time to palliative androgen deprivation therapy, and cure of the patient. Currently, there is not enough high-quality data on treatment and effectiveness of metastasis-directed therapy. Terminology standardization, use of the full potential of positron emission tomography/computed tomography imaging with prostate-specific membrane antigen, its combination with molecular and genetic tests, and stratification of risk factors for each individual patient are necessary.
Therapeutic landscape of several genitourinary malignancies has been revolutionized by the development of immune checkpoint inhibitors; however, the utility of immunotherapies in prostate cancer has been limited, partly due to the immunologically “cold” tumor microenvironment of prostate cancer. As of today, pembrolizumab is the only immune checkpoint inhibitor approved for treatment of metastatic castration-resistant prostate cancer (mCRPC) in a select group of patients with high microsatellite instability, deficient mismatch repair, or high tumor mutational burden. Currently, several combinations with immune checkpoint inhibitors involving radioligands, radiotherapy, PARP inhibitors, interleukin inhibitors, and cancer vaccines are being explored for potential synergistic effect. Furthermore, B7-H3 is an alternative checkpoint that may hold promise in treatment of mCRPC. This review aims to summarize previous monotherapy and combination therapy trials of immune checkpoint inhibitors as well as novel immunotherapy combinations and treatment targets in mCRPC.
TOPICAL PROBLEM
Numerous studies indicate a decrease in overall survival among cancer patients who have developed thromboembolic complications. The article presents a review of literature on thromboembolic complications in patients with kidney, bladder, and prostate cancer. The analysis of publications indicates a variety of risk factors and heterogeneous frequency of thromboembolism in patients with malignant neoplasms of the genitourinary system. Prevention of thromboembolism is carried out at all stages of treatment: outpatient, after surgery, during chemotherapy, but is accompanied by a fairly high risk of hemorrhagic complications and recurrences. Direct oral anticoagulants are an alternative to low-molecular-weight heparin for prevention of cancer-associated thromboembolism due to their convenience, efficacy and safety for most patients. An important task is to select patients for primary thromboprophylaxis based on stratification of the risk of thromboembolic complications using prognostic scales.
ISSN 1996-1812 (Online)