Background. Maintenance therapy with avelumab is the standard of care for patients with metastatic and locally advanced inoperable urothelial carcinoma who have not progressed with platinum-based chemotherapy. Between 2021 and 2024, 40 patients with metastatic and locally advanced inoperable urothelial carcinoma were treated at the N.A. Lopatkin Research Institute of Urology and Interventional Radiology and the Moscow Center for Immunotargeted Therapy. Their disease was confirmed to be controlled after 4-6 courses of platinum-based chemotherapy followed by maintenance therapy with avelumab. Aim. To evaluate the efficacy and tolerability of maintenance therapy with avelumab in metastatic urothelial cancer in real-world clinical practice. Materials and methods. The study included 11 women (27.5 %) and 29 men (72.5 %), aged 39 to 80 years. Mean age was 63.95 +/- 10.9 years, median age was 65.5 (interquartile range 58.3-72.0 years). Patients were divided by primary tumor location as follows: bladder cancer (24 patients; 60 %), upper urinary tract cancer (14; 35 %), and multiple primary cancer (combined lesions) (2; 5 %). All patients received 4-6 cycles of platinum-based chemotherapy in the first line, with 28 (70 %) patients starting with the gemcitabine + cisplatin combination. Gemcitabine + cisplatin was used throughout treatment in 24 cases (60 %), gemcitabine + carboplatin (30.0 %) was used in 12 cases, and 4 (10 %) patients underwent a switch from gemcitabine + cisplatin to gemcitabine + carboplatin. Chemotherapy resulted in complete response in 6 patients (15 %), while the remaining patients experienced partial response (37.5 %) or stable disease (47.5 %). Progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method from the start of first-line chemotherapy. A subgroup analysis was performed to assess 12-, 24-, and 36-month PFS, taking into account prognostic factors. Results. The median follow-up was 23.3 months (6 to 54, interquartile range 27.1-45.8 months). Median PFS from the start of chemotherapy was 18 months (95 % confidence interval (CI) not reached-11 months). PFS at 12, 24, and 36 months was 63.2 % (95 % CI 45.9-76.3), 49.3 % (95 % CI 32.5-64.0), and 45.8 % (95 % CI 29.1-61.0), respectively. PFS from the start of avelumab therapy was 14 months. Median OS was not reached at the time of analysis (95 % CI not reached-22 months). OS at 12, 24, and 36 months was 88.9 % (95 % CI 73.1-95.7), 58.3 % (95 % CI 39.5-73.0), and 54.4 % (95 % CI 35.6-69.8), respectively. Better PFS rates were demonstrated in patients with a complete response to platinum-based therapy compared with those with partial response or stable disease, in patients receiving cisplatin compared with carboplatin, in patients with lymph node-only metastases compared with other metastatic sites, and in primary bladder tumors compared with upper urinary tract cancer. Immune-related adverse events were reported in 50 % of patients, but only in 7.5 % (n = 3) of cases did these lead to avelumab discontinuation. Therapy interruption occurred in 1 patient. Conclusion. Real-world clinical practice has demonstrated that maintenance therapy with avelumab is an effective strategy for long-term disease control in patients with metastatic and locally advanced inoperable urothelial cancer, with an acceptable immune-mediated toxicity profile.
Background. The decade-long use of checkpoint inhibitors in real-world clinical practice in Russia allowed to treat hundreds of patients with urothelial malignancies. The AURORA-RU Phase IV observational Russian study was initiated to evaluate the efficacy of atezolizumab in patients with urothelial carcinoma resistant to platinum-based chemotherapy. This article is based on an analysis conducted at a median follow-up of 60.7 months and provides data on treatment efficacy in Russian patients receiving second-line and subsequent lines of systemic therapy. Aim. To evaluate the clinical efficacy of atezolizumab monotherapy in patients with urothelial carcinoma of the upper and lower urinary tract progressing on platinum-based chemotherapy in a real-world clinical setting. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Secondary endpoints included subgroup analyses of efficacy based on the line of therapy (including the subgroup with early progression after neo/adjuvant chemotherapy [NACT/ACT]), age cohort, metastatic sites, and primary tumor location (bladder vs. upper urinary tract). Materials and methods. The study included data from 152 patients with verified muscle-invasive locally advanced and metastatic urothelial carcinoma who received PD-L1 inhibitor (atezolizumab) monotherapy across 13 centers in the Russian Federation between 2019 and 2025. Atezolizumab treatment was administered to patients who progressed on platinum-based chemotherapy. More than half of the patients (55.9 %) were over 65 years of age. The cohort consisted of 75.0 % men and 25.0 % women. The majority of patients (78.3 %) had a primary tumor located in the bladder. PD-L1 inhibitor therapy was administered as second-line treatment in 57.9 % of cases, while one in five patients (21.7 %) received third-line treatment. In 86.8 % of cases, treatment was administered without prior assessment of PD-L1 expression levels. Results. In the overall cohort, the median PFS reached 5.5 months, with 36-month and 48-month PFS rates of 15.9 % and 9.9 %, respectively. The median OS was 12.0 months; 21.9 % of patients survived 3 years, and 14.3 % of patients remained under observation for five years. In patients transitioning to immuno-oncology treatment after rapid progression following NACT/ACT, the median OS was 17.4 months. The median OS for second-line therapy was two-fold higher than for third-line therapy: 13.9 months versus 6.1 months. High treatment efficacy was noted in patients over 70 years of age (median PFS of 8.7 months; median OS of 14.9 months). Conclusion. In real-world practice, PFS and OS rates were comparable to those reported in registration trials and other real-world evidence studies. The lack of PD-L1 expression testing generally did not affect the efficacy of immuno-oncology therapy in patients with urothelial carcinoma.
Aim. To determine clinical and morphological characteristics of the tumors invisible on magnetic resonance imaging (MRI) in patients with prostate cancer (PCa) who underwent robot-assisted radical prostatectomy. Materials and methods. Retrospective analysis of MRI images of 151 patients with PCa after robot-assisted radical prostatectomy between 2022 and 2023 was performed. Series of T2-weighted, diffusion-weighted and dynamic contrast-enhanced images in accordance with the PI-RADS v.2.1 (Prostate Imaging Reporting and Data System) protocol were obtained. All MRI scans were interpreted by two radiologists with more than 20 years of experience. Statistical analysis was performed using IBM SPSS Statistics 25.0 software. Results. Among 151 patients of the study cohort, 25 (17 %) patients did not have PI-RADS 3-5 lesions, while 126 (83 %) had them (& rcy; = 0.121). The patients had statistically significant differences in the prostate-specific antigen levels: in the group with lesions confirmed by multiparametric MRI (mpMRI) compared to the group without lesions the level of this tumor marker was significantly higher (median 7.15 [5.0-11.6] ng/mL; 95 % confidence interval (CI) 8.51-11.86 and 5.9 [4.13-8.1] ng/mL; 95 % CI 4.19-12.05, respectively; & rcy; = 0.034). The incidence of tumors with Gleason score 6 and 7 depending on the type of prostate cancer on mpMRI was determined. For focal lesions, the incidence of neoplasms with Gleason score 7 was higher (n = 92) than in the group without lesions (n = 14). Prostatic lesions per mpMRI were significantly more common in patients with potentially more aggressive forms of PCa (high prostate-specific antigen level, Gleason score >= 7, high tumor volume per morphological examination). In the absence of confirmed prostatic lesions by mpMRI, in 72 % of patients, tumor volume did not exceed 37.5 % of the resected organ per morphological examination. Additionally, in this case less aggressive characteristics and smaller volume of the tumor were observed compared to lesional disease. Conclusion. The results confirmed high incidence of aggressive forms of the disease in MRI-visible PCa. In the group of MRI-invisible tumors, more than half of neoplasms had Gleason score 7. These data do not allow to unequivocally classify patients with MRI-invisible cancer into the favorable prognosis group.
Background. Bladder cancer (BC) is one of the most common cancers worldwide, representing an urgent problem of modern oncology. Various external and internal environmental factors increase the disease risk. Genetic susceptibility to BC is unquestioned and actively researched nowadays. Aim. To analyze current advances in genetic factors of BC and to assess the prospects for further research in this area. Materials and methods. A systematic analysis of modern literature available in the PubMed database was conducted. Results and conclusion. A small part of BC cases is associated with hereditary syndromes, which are characterized by BC development. Genes regulating cellular metabolism, DNA repair, and cell cycle are associated with BC. Today, there is a clear understanding that high-risk genes are rarely involved in the development of most BC cases, but there are many polymorphic loci with low penetrance and moderate effects that acting together increase BC risk, indicating a complex polygenic inheritance pattern for this disease.
Background. Non-clear cell renal cell carcinoma (nRCC) is a heterogeneous group of malignancies, accounting for approximately 15-20 % of all kidney tumors. Results of the KEYNOTE-B61 phase II trial demonstrated high antitumor activity and a favorable safety profile for the combination of lenvatinib and pembrolizumab in patients with nRCC. Due to these clinically significant results, the combination of lenvatinib and pembrolizumab has been included in international and Russian guidelines, becoming the preferred first-line treatment for metastatic nRCC. Aim. To confirm the efficacy of the combination of lenvatinib and pembrolizumab in real-world clinical practice at the Leningrad Regional Clinical Hospital in patients with nRCC. Materials and methods. In this study, we conducted a retrospective analysis of real-world clinical data describing 10 patients with nRCC treated with combination therapy of lenvatinib and pembrolizumab. Results. The objective response rate was 40 %, including 10 % of complete responses. Median progression-free survival was not achieved (follow-up 36-49 months for most patients). At the last follow-up, all patients remained progression-free. No new safety signals were identified. Conclusion. The experience of the Leningrad Regional Clinical Hospital with the combination of lenvatinib plus pembrolizumab for the treatment of nRCC has confirmed its efficacy and safety in real-world clinical practice in a Russian patient cohort. The safety profile was predictable and manageable, with no treatment-related lethal outcomes. These findings support that the combination of lenvatinib plus pembrolizumab should be considered a standard first-line therapy for patients with advanced nRCC.
