e17084 Background: Although the combination of androgen deprivation therapy (ADT) with an androgen receptor pathway inhibitor (ARPI) is the established standard of care for patients with high-volume metastatic hormone-sensitive prostate cancer (mHSPC), the added benefit of intensifying therapy with docetaxel to create a triplet regimen remains undefined. In the absence of direct comparative randomized trial data, real-world evidence (RWE) is crucial to inform this treatment intensification decision. Methods: Our multicenter retrospective study included patients with high-volume mHSPC (by CHAARTED criteria) who initiated doublet (ADT + ARPI) or triplet (docetaxel + ADT + ARPI) therapy between 2022 and 2024. To mitigate confounding, patients were matched using cardinality matching at a 2:1 ratio. The primary endpoint was 2-year progression-free survival (PFS). Secondary end-points was overall survival (OS). PFS was defined as the time from treatment initiation to clinical/radiological progression, commencement of subsequent systemic therapy, or death from any cause. Results: Of 183 patients 122 received triplet (ADT+docetaxel+abiraterone or ADT+docetaxel+enzalutamide), 61 doublet therapy (ADT+enzalutamide or apalutamide). The triplet regimen demonstrated superior outcomes: 2-year PFS was 75.9% vs. 48.9% (HR 0.50, 95% CI 0.31–0.80) and 2-year OS was 82.9% vs. 66.8% (HR 0.47, 95% CI 0.28–0.79). The benefit of docetaxel addition was pronounced in patients aged < 65 years (PFS: HR 0.28, 95% CI 0.12-0.68; OS: HR 0.17, 95% CI 0.06-0.54), patients with liver metastases (PFS: HR 0.16, 95% CI 0.04-0.68; OS: HR 0.12, 95% 0.02-0.61), Gleason score ≥8 (PFS: HR 0.49, 95% 0.29-0.82; OS: HR 0.45, 95% CI 0.25-0.84) and detectable baseline erythroblasts in blood sample (PFS: HR 0.29, 95% CI 0.11-0.76; OS: HR 0.24, 95% CI 0.07-0.77). No significant survival difference between triplet and doublet therapy was found in patients > 65 years or with metachronous high-volume disease. Conclusions: Real-world data confirms the superiority of triplet therapy for the majority of patients with synchronous high-volume mHSPC. Treatment intensification can be effectively guided by routine clinical characteristics.

ABSTRACT Background This ambispective study was designed to assess the efficacy and safety of avelumab maintenance in a real‐world population of patients with metastatic urothelial cancer (UC). Methods Patients with metastatic UC and measurable disease that had not progressed following first‐line platinum‐based chemotherapy were treated with maintenance avelumab (800 mg administered every 2 weeks). The primary endpoint was overall survival (OS). Results A total of 110 patients were enrolled. The majority of patients were male (81%), with a median age of 65 years (range, 36–84). The median OS was not reached, with a 1‐year OS rate of 78.7%. The median PFS was 9.5 months (95% CI, 7.8–11.2 months). The ORR to first‐line chemotherapy was 48.2%, and an additional 34.6% of patients responded to avelumab therapy (16 complete and 22 partial responses). Grade 3 adverse events during avelumab therapy were experienced by 11.8% of patients. Conclusions These findings demonstrate similar efficacy and safety of avelumab in a real‐world setting when compared to data from pivotal study. Trial Registration: KCRB registry number: RAVE‐Bladder

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ)

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ).

В данном разделе указаны критерии оценки клинической значимости применения дорогостоящей противоопухолевой лекарственной терапии в соответствии со шкалой, разработанной экспертной группой (см. стр. 7). В тексте они обозначены, как магнитуда клинической значимости (МКЗ)

Objective: This study aimed to assess the expression of platelet-derived growth factor receptors alpha and beta (PDGFR!/") in primary tumor cells of patients with renal cell carcinoma (RCC). Methods: Platelet-derived growth factor receptors alpha and beta expression was analyzed in RCC specimens from 65 RCC patients (pT1a-T4NanyMany) using immunohis- tochemistry. Expression levels were quantified using the semi-quantitative H-score (HS) method, and correlations between PDGFR!/" expression and tumor characteris- tics were evaluated. The impact of PDGFR!/" expression on patient survival was also examined. Results: Platelet-derived growth factor receptor alpha was expressed in the cytoplasm and membrane of 58.5% of primary RCC cells, with an HS of 62.9 ± 8.4, significantly higher than PDGFR" expression (44.6%; 26.6 ± 5.3; P > .05). Platelet-derived growth factor receptor alpha expression correlated with tumor grade (r = 0.471; P < .0001) and the pN+ category (r = 0.280; P = .024). Platelet-derived growth factor receptor beta expression correlated with tumor grade (r = 0.286; P = .021), venous tumor thrombosis (r = 0.263; P = .034), M+ category (r = 0.305; P = .014), and adrenal metastases (r = 0.306; P = .041). Neither PDGFR! nor PDGFR" expression levels influenced patient survival. Conclusion: Platelet-derived growth factor receptor alpha was more highly expressed in RCC cells compared to PDGFR". Overexpression of PDGFR!/" was associated with higher tumor grade and advanced RCC stages, though it did not affect patient survival.

Aim. To establish the criteria of selection for extracorporeal partial nephrectomy (EPN) among patients with malignant tumors involving renal parenchyma. Materials and methods. The study included data of 34 patients undergone 36 EPNs (2 [5.8%] bilateral) for absolute indications in 32 (94.2%) and relative indications – in 2 (5.8%) cases. The median age of the patients was 49 (31–61) years, and 24 (70.6%) were males. 33 (97.1%) patients were diagnosed with renal cell carcinoma, 1 (2.9%) – with primary retroperitoneal leiomyosarcoma involving a solitary kidney. No regional metastases were detected in any patients; 2 patients were diagnosed with solitary metastases in the adrenal gland. In all patients EPN was performed (2 [5.8%] – with adrenalectomy); the surgery was completed in 35 (97.2%) patients. No additional anti-tumor treatment was administered in any patient. The median follow-up was 65.6 months. Results. The median surgery time was 674 (360–870) min, and the median blood loss was 2100 (500–7000) mL. The rate of postoperative complications of EPN was 82.9% (30/35), including 48.6% (17/35) of grade 1–4 and 8.6% (3/35) of grade 5 complications. Severe acute kidney injury was reported in 68.0% (25/33) of patients with completed EPN. Renal replacement therapy was required in 45.5% (15/33) of cases. The rate of postoperative autograft loss was 17.1% (7/35). One patient received intermittent hemodialysis (7 years after EPN). 5-year overall survival of 33 patients with completed EPN was 64.4%; the 5-year specific and disease-free survival of patients with renal cell carcinoma was 85.5% and 54.3%, respectively, and 5-year hemodialysis-free survival in patients discharged with autograft was 76.2%. Conclusion. EPN is indicated only for carefully selected patients with absolute indications for organ-preserving treatment, with massive multifocal centrally located malignant tumors in the renal parenchyma, the radical removal of which in situ is technically impossible.

Objective: to evaluate the efficacy of first-line systemic therapy administered in real clinical practice to patients >75 years old with prostate cancer (PCa).Material: the retrospective study included data from 315 patients >75 years old (median age — 84 (75-99) years) with hormone-sensitive PCa (HSPCa) who received antitumor therapy. Non-metastatic HSPCa (nmHSPCa) was observed in 223 (70,8%) patients, while metastatic HSPCa (mHSPCa) — in 92 (29,2%) patients. In 8 (3,6%) cases of nmHSPCa, bicalutamide monotherapy was prescribed, while androgen deprivation therapy (ADT) was administered in 215 (96,4%) cases (intermittently — 164 (73,5%)). All 92 patients with mHSPC received ADT, including in combinations corresponding to current clinical recommendations — in 38 (41,3 %) cases (with docetaxel — 17 (18,4 %), abiraterone acetate — 7 (7,6 %), enzalutamide — 10 (10,9 %), apalutamide — 1 (1,1 %)). The median follow-up time for patients with nmHSPC was 64,2 (2,1-275,7) months, for patients with mHSPC — 48,6 (1,0-234,3) months.Results: the median duration of the 1st line of therapy for nmHSPC was 40,6 (1,0-243,8) months. In nmHPRPC, PSA reduction by>90% during the first line of therapy was seen in 67,3 % of patients. Five-year survival of patients with nmHPRPC without PSA progression (PFPS) reached 70,8%, progression-free survival (PFS) — 70,8%, metastasis-free survival (MFS) — 85,0%, specific survival (SS) — 97,3% and overall (OS) — 91,5%. Continuous ADT in lowand intermediate-risk nmHPRPC reduced PFS compared to intermittent therapy (p = 0.014), but did not affect MFS, SS and OS. The median duration of the first line of therapy for mHPRPC was 14,3 (1,1-137,7) months. In mHSPC, the frequency of PSA decrease by>90% during the first line of therapy was 38,0%. In patients with mHSPC, the 4-year PFSSA was 50,1%, DFS — 50,1%, DFS — 83,5% and OS — 77,2%. In mHSPC, ADT compared with combination therapy reduced DFS (p = 0.018), DFS (p = 0.053) and OS (odds ratio 3.675 (95% confidence intervals: 1.001-13.489); p = 0.008). No significant effect of the combination drug on the survival of patients with mHSPC was found.Conclusions: in elderly patients with nmHSPC, intermittent ADT is not inferior to continuous ADT in terms of OS. In patients > 75 years old, combination therapy based on ADT with docetaxel or androgen signal inhibitors provides an increased OS compared to ADT alone.

Background. The clinical course of non-muscle-invasive bladder cancer is characterized by a tendency to develop local recurrences and the ability to tumor progression. The most effective method of preventing disease progression after transurethral resection of the bladder in patients of intermediate and high-risk groups is intravesical therapy with BCG antitumor vaccine containing attenuated Mycobacterium tuberculosis. Taking into account the increasing incidence non-muscle-invasive bladder cancer in Moscow, the organization of adequate use of BCG vaccine in clinical practice requires the involvement of significant organizational and human resources. Aim. To develop and validate an organizational model for the delivery of BCG therapy for non-muscle-invasive bladder cancer at an outpatient cancer care center using hospital-substitution technologies. Materials and methods. In the period from June 2023 to May 2024, BCG therapy has been performed in Oncology Center №1 of Yudin Moscow City Hospital in 180 patients with verified non-muscle-invasive bladder cancer of intermediate and high-risk groups. Results. The study revealed a trend towards an increase in the absolute number of early bladder cancer in Moscow in the period 2018–2023. According to clinical guidelines, treatment of patients with non-muscle-invasive bladder cancer includes determination of the risk of recurrence and tumor progression with subsequent formation of indications for intravesical BCG therapy. The regimen of administration depending on the risk of recurrence includes 18–42 instillations for 12–36 months after transurethral resection of the bladder with follow-up examinations every three months. The procedure of intravesical BCG therapy takes 1–2 hours and does not require hospitalization. An organizational model of treatment an outpatient cancer care center based on various forms of hospital-substitution technologies is presented. Conclusion. Intravesical BCG therapy is a highly demanded method for the treatment of non-muscle-invasive bladder cancer. This method can be widely used in outpatient settings through the use of hospital-substitution technologies.

Aim To evaluate the safety and toxicity of lenvatinib with pembrolizumab in unselected patients with advanced renal cell carcinoma (RCC). Materials and methods. The Russian phase IV observational study included 151 patients with advanced RCC who received lenvatinib with pembrolizumab in a standard dose regimen in 36 clinical centers of the Russian Federation. Most patients were diagnosed with clear cell RCC (n=145, 96.0%), with synchronous (n=77,51.0%) metastasesof more than one location (n=111,73.5%), removed primary tumor (n=98, 64.9%) and were classified into intermediate and poor IMDC prognostic groups (n=111, 73.5%). Median follow-up was 9.6 (1—68) months. Results. Any adverse events (AEs) were noted in 109 (72.2%), grade ≥3 AEs-in 26 (17.2%), serious AEs-in 9 (6.0%) of 151 patients. There were no deaths caused by AEs. AEs were an indication for lenvatinib dose reduction in 32 (21.2%), a dose interruptions in lenvatinib treatment in 21 (13.9%), and lenvatinib discontinuation in 2 (1.3%) cases. A dose interruptions in pembrolizumab therapy due to AEs was necessary in 15 (9.9%) cases. Both combination drugs were discontinued due to toxicity in 10 (6.6%) cases. AEs were assessed as immune-mediated in 24 (15.9%) patients (grade 3-4 - n=7, 4.6%) and required the prescription of high doses of glucocorticosteroids in 2 (1.3%) patients. Conclusions. A Russian observational study confirmed the acceptable safety profile of lenvatinib plus pembrolizumab therapy in patients with advanced RCC.

Aim. To compare of efficacy and safety of combined immune therapy (dual immune-oncology – IO combination therapies, IO-IO) and immune targeted therapy (ITT) in the first line treatment of patients with advanced renal cell carcinoma (RCC) treated in real world clinical practice. Materials and methods. The ambispective study enrolled patients with metastatic RCC aged ≥18 years, with measurable neoplastic lesions, who were treated with first-line IO-IO therapy or ITT. The primary endpoint was progression-free survival (PFS). Results. The study included data from 126 patients treated with IO-IO [46 (36.5%) patients of the IMDC intermediate and poor prognostic groups] or ITT [80 (63.5%) patients of all IMDC prognostic groups]. In a median follow-up of all patients of 16.1 (0.1–44.9) months, the median PFS was 16.1 (10.9–21.3) months, the median overall survival (OS) was not reached; one-year OS was 83.0%; the objective response rate on the first line of therapy was 44.4% with a complete response rate of 3.2%. The rate of tumor control was 88.1%. In the overall population, ITT versus IO-IO provided a significant benefit in terms of ORR (51.2% vs 32.6%; p=0.032), PFS (median 22.9 months vs 8.0 months; p=0.004) and one-year OS (87.5% vs 65.2%; p=0.042). In the IPTW population, multivariate analysis confirmed the independent prognostic significance of the treatment regimen for PFS (hazard ratio, 2.3; 95% confidence interval, 1.1–4.8; p=0.037) and OS (hazard ratio, 2.3; 95% confidence interval 1.1–4.8; p=0.037). No difference in the safety profile of IO-IO and ITT was identified. Conclusion. The results support the hypothesis that ITT is more effective than IO-IO in the first-line treatment of advanced RCC in patients of IMDC intermediate and poor prognostic groups.

Positive surgical margin is observed in approximately 10% of specimens after radical surgery for locally advanced urothelial carcinoma, and is associated with an increased risk of locoregional recurrence, metastases, and death. R+ patients are a heterogeneous group of patients requiring individual treatment approaches. There is no standard of care for R+ patients; acceptable options include observation, removal of residual tumor, postoperative chemotherapy (CT), immunotherapy (IT), radiation therapy (RT), and chemoradiotherapy (CRT). The choice of treatment plan depends on the location and characteristics of the primary tumor, use of neoadjuvant chemotherapy (NACT) before surgery and the response to it, the pathological response, the presence of detectable residual tumor, as well as the potential tolerability of immediate postoperative treatment.

Background. Combination therapy is the standard of care for intermediate and poor prognosis metastatic renal cell carcinoma. In the IMDC prognostic classification, tumor stage and histological type are not considered due to the lack of independent impact on overall survival. The CLEAR study demonstrated the efficacy of lenvatinib and pembrolizumab combination in long-term treatment outcomes, including overall survival in poor prognosis compared to sunitinib. The KEYNOTE-B61 study demonstrated high efficacy of this combination in patients with non-clear cell renal cell carcinoma. Aim. To evaluate the efficacy of the combination of lenvatinib and pembrolizumab in patients with high tumor burden and non-clear cell histotypes. Materials and methods. This prospective observational study included 54 patients with metastatic renal cell carcinoma who received a combination of lenvatinib and pemrolizumab in the first line between 2022 and May 2024 in oncology clinics of the Moscow Department of Health. Clear cell histotype was represented in 79.6% of cases, 14.8% had papillary cancer, and 5.6% of patients had chromophobe cancer. The primary endpoint was the objective response rate. Results. The objective response was assessed in 50 patients. The objective response rate was 38%, including 2% complete response according to RECIST 1.1, disease progression was in 8% of patients. The median depth of response was -25% (from -100% to +28). The median time to response was 12.4 weeks (1.1–38.3). Conclusion. The efficacy of the combination of lenvatinib and pembrolizumab in real-life clinical practice outside the inclusion criteria of the CLEAR study is clinically significant and allows us to expect improvement even in patients with a large volume of metastatic process and non-clear cell histotype, but the expected benefit in patients with unsatisfactory somatic status remains disputed.

Objective: to re-evaluate the efficacy and safety of lenvatinib with pembrolizumab in unselected Russian renal cell carcinoma (RCC) patients, included in the phase IV study, in a median follow-up extended to 17.1 months. The primary end point was progression-free survival (PFS), secondary end points were overall survival (OS), objective response rate (ORR) and duration of response (DOR), disease control rate (DCR) and its duration, as well as safety. Materials and methods. The study included medical data of 165 patients with verified advanced RCC who received lenvatinib with pembrolizumab in 36 centers of the Russian Federation from 05.02.2018 to 25.07.2024. The median age was 60 (20-76) years, the male to female ratio was 2.3:1. The majority of patients had Karnofsky performance status >= 80 % (74.6 %), clear cell RCC (93.3 %) without sarcomatoid differentiation (93.3 %), metachronous metastases (50.9 %) localized in >1 organ (75.2 %), were nephrectomized (63.0 %) and did not receive antitumor therapy (91.0 %). At the time of lenvatinib with pembrolizumab therapy start 40 patients (24.2 %) were classified into International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable prognostic group, 92 (55.8 %) in the intermediate prognostic group, and 33 (20.0 %) in the poor prognostic group. The median follow-up was 17.1 (1.5-72.9) months. Results. The median PFS achieved 24.0 (18.7-29.3) months, 17-month PFS- 60.5%. The median OS was 48.9 (18.5- 79.2) months, 17-month OS - 76.1 %. Objective response was registered in 46.0 % of patients including 2.4 % complete responders; the DCR was 92.1 %. The median DOR was 16.6 (2.1-72.9) months, duration of disease control - 14.3 (2.1-72.9) months. Confirmed dynamics of change in the sum of tumor foci diameters was recorded in 152 patients, while the median change was -25 % (from -100 % to +29 %). Any decrease in the sum of tumor foci diameters occurred in 69.1 % of cases. The incidence of any adverse events (AE) was 78.2 %, severe AE - 24.2 %, and serious AE - 9.7 %. Immune-mediated AEs developed in 17.0 % of cases and AE grades 3-4 in 6.7 % of cases. Mortality from AEs was 1.2 %. Conclusion. Compared with the registration study, in real-world clinical practice in patients with advanced RCC the lenvatinib with pembrolizumab provides a lower ORR with comparable PFS and OS rates and demonstrates a satisfactory safety profile.

e16569 Background: The RAVE-Bladder study was designed to assess the efficacy and safety of avelumab maintenance in patients with metastatic urothelial carcinoma in a real-world population. Methods: In this non-interventional, ambispective study, eligible patients had metastatic urothelial carcinoma and measurable disease that had not progressed with first-line platinum-based chemotherapy. Patients received maintenance avelumab according to a standard regimen (800 mg, administered every 2 weeks). Tumor imaging was performed at baseline and then every 12 weeks. The primary endpoint was overall survival (OS) at the initiation of avelumab treatment, while secondary endpoints included progression-free survival (PFS), objective response rate (ORR), and safety. Results: At data cutoff (February 02, 2024), 110 patients (81% male, 19% female) were recruited from 21 sites and median follow-up was 9.71 months. Median age was 65 (range, 36-84) years. All patients had confirmed urothelial carcinoma (high grade, 62.8%). Primary tumor site was upper urinary tract in 26 (23.6%) and bladder in 84 (76.4%) cases. Forty-five (40.9%) patients had radical surgery; 68 (61.8%) had metastatic disease at time of diagnosis; 44 (40%) had 2 and more metastatic sites. First-line chemotherapy included gemcitabine + cisplatin, gemcitabine + carboplatin, cisplatin only, carboplatin only, and MVAC in 51 (46.4%), 32 (29%), 19 (17.3%), 7 (6.4%), and 1 (0.9%) patients, respectively. Median number of chemotherapy cycles was 4 (range, 3-9) and median number of avelumab infusions was 16 (range, 2-43). ORR to chemotherapy was 48.2%. An additional 38 patients (34.6%) responded to avelumab therapy (16 CR, 22 PR). Median OS was not reached and 1-year OS rate was 78.7%. Median PFS was 9.5 months (95% CI 7.8 – 11.2 months). Thirteen (11.8%) patients experienced grade 3 adverse events during avelumab therapy. Conclusions: The findings illustrate the favorable tolerability of maintenance therapy with avelumab, a remarkable progression-free interval subsequent to standard platinum-containing chemotherapy and prominent additional response rate among patients with metastatic urothelial carcinoma. Ongoing follow-up continues to provide additional insights. Clinical trial information: KCRB01012022 .

Aim. To evaluate the results of radical surgical treatment and radiotherapy in patients with non-metastatic prostate cancer at age >= 75 years. Materials and methods. The retrospective study included data from 151 patients >= 75 years with verified non-metastatic prostate cancer who underwent radical prostatectomy (RP) or external beam radiotherapy (EBRT). Median age was 81.0 (75.0-97.0) years. Median Charlson comorbidity index was 7 (4-12). Median baseline prostate specific antigen (PSA) level was 11.0 (1.8-172.0) ng/mL. Prostatic adenocarcinoma was verified (ISUP grade 4-5 - 30 (19.9 %)) in all patients. & scy;& Tcy; category was & scy;& Tcy;3-4 in 37 (24.5 %), cN1 category was diagnosed in 10 (6.6 %) patients. The groups of unfavorable intermediate, high and very high risk included 93 (61.6 %) patients. Radical treatmentwas performed in all cases: RP in 38 (25.2 %), EBRT in 113 (74.8 %) patients (109 (72.2 %) men completed EBRT). Adjuvant treatment was administered in 8 (21.1 %) patients who underwent surgery. In the EBRT group neoadjuvant androgen-deprivation therapy (ADT) was administered in 74 (65.5 %), adjuvant ADT in 79 (70.0 %) cases. Treatment groups were matched by the main characteristics (& rcy; >0.05 for all) excluding lower baseline PSA in the RP group (& rcy; = 0.013). Median follow-up was 46.2 (1.5-234.2) months for all patients. Results. RP complications were registered in 3 (7.8 %), EBRT complications - in 7 (6.2 %) patients. No serious or lethal adverse event was observed. Recurrences were diagnosed in 9 (23.7 %) patients after surgery and in 26 (23.9 %) of 109 patients who completed EBRT. In the total study population, 4-year recurrence-free, cancer-specific, overall, and cardiac-specific survival rates were 74.5; 96.3; 91.2 and 90.8 %, respectively. The only factor significantly decreasing overall survival was Charlson comorbidity index >= 8 (& rcy; = 0.05). Significant decrease of recurrence-free survival was observed in the surgery group compared to the EBRT group (& rcy; = 0.032). It did not translate into decreased cancer- specific and overall survival (& rcy; >0.05 for all). There was no significant difference in cardiac-specific survival between the groups (& rcy; = 0.626). Significant unfavorable prognostic factors of recurrence-free survival in the EBRT group included & scy;N1 category (& rcy; = 0.045), very high risk (& rcy; = 0.049), and EBRT dose. Conclusion. RP and EBRT in elderly patients with non-metastatic prostate cancer receiving treatment in real clinical practice have acceptable safety profile and provide effectiveness comparable to the historical data on patients not sampled by age. The optimal candidates for radical treatment are men with Charlson comorbidity index <8.