Combination therapies integrating immune checkpoint inhibitors (ICIs) with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs), or dual ICI regimens, currently represent the standard of care for advanced clear cell renal cell carcinoma (ccRCC). However, in most favorable-risk patients according to the IMDC classification-particularly those with a low disease burden and without disease-related symptoms-first-line monotherapy with VEGFR-TKIs remains a valid option. This review summarizes the preclinical and clinical evidence supporting this approach, with the aim of guiding oncologists in personalizing therapy while minimizing overtreatment and toxicity.

Background: Accumulating evidence demonstrates that inflammatory responses play a critical role in tumor progression, invasion, and metastasis. In recent years, systemic immune-inflammatory (SII) markers have emerged as valuable tools for evaluating tumor grade and prognosis in solid tumors. To assess SII scores associated with neoplasm-related grading and staging in order to investigate the incidence rate in SII levels and cancer-related aggressiveness. Methods: The present review was recorded in Figshare system with id no. 10.6084/m9.figshare.31029121. Observational studies recording grading and staging differences (advanced III–IV vs. early 0–II) in SII values among cancer patients were included in the present review. Frequencies were collected among cancer patients, along with low and high SII levels and related grading and staging scores. Results: A total of ten studies were included in the present review. Considering cancer grading classification and SII levels, our data showed significant associations not recorded in all the selected studies. Additionally, high SII values appeared to be significantly associated with advanced-stage cancer (stages III–IV), while lower SII values were associated with an increased probability of early-stage tumors (stages 0–II), (p < 0.05). Conclusions: The SII marker has shown potential predictive value in cancer. However, the SII is a relatively novel index in which a direct causal effect on tumor initiation or subsequent disease progression remains to be comprehensively investigated.

BACKGROUND:Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous group of rare malignancies with limited evidence guiding systemic therapy. The recent introduction of immune checkpoint inhibitors (ICIs) and their combinations with tyrosine kinase inhibitors (TKIs) has shown promising results, but real-world data remain scarce. METHODS:We retrospectively collected clinical and pathological data from patients with metastatic nccRCC included in the Italian Meet-URO-23/I-RARE database and from Vall d'Hebron Institute of Oncology (VHIO). Prognostic factors for overall survival (OS) were analyzed using univariate and multivariate Cox regression. Treatment outcomes were assessed by histology and therapeutic regimen. RESULTS:A total of 156 patients were included: papillary (56.4%), chromophobe (22.4%), translocated (10.9%), and unclassified (10.3%) RCC. Median OS was 17.5 months (95%CI 14.7-27.6) and median progression free survival (PFS) 10.2 months (95%CI 7.6-13.7). Patients treated with ICI-combinations (ICI plus ICI or ICI plus VEGF-TKI) showed significantly improved survival (median OS not reached vs 14.7 months for other regimens, p = 0.0053). The overall objective response rate (ORR) and disease free survival (DFS) for ICI+TKI was 53.3% (16/30 evaluable) and 93.3% (28/30), with ORR of 55.5% (10/18) in papillary and 46.1% (6/13) in chromophobe subtypes. In the overall ICI-combination group, ORR was 48%. In multivariate analysis, International Metastatic RCC Database Consortium (IMDC) score, presence of bone metastases, and type of first-line therapy were independently associated with OS. CONCLUSIONS:In this large international real-world cohort, ICI-based combinations demonstrated superior outcomes compared to other regimens in metastatic nccRCC. These results reinforce the role of immunotherapy combinations as a preferred first-line approach and confirm the IMDC score as a reliable prognostic tool in this population.

CONTEXT:With new treatment strategies approved in metastatic hormone-sensitive prostate cancer (mHSPC), heterogeneity across trials hinders the physicians' choice for first-line treatment. OBJECTIVE:We conducted a systematic review and network meta-analysis to assess the efficacy of currently approved treatments for mHSPC stratifying patients according to their disease burden (high- vs. low-volume as per CHAARTED criteria) and onset of metastatic disease (synchronous vs. metachronous). INTERVENTION:Eleven randomized controlled trials (RCTs) published until October 30, 2024 were included. Treatment regimens were grouped as triplets for combinations of docetaxel, androgen receptor pathway inhibitors (ARPIs) and androgen-deprivation therapy (ADT), separate doublets for docetaxel plus ADT, ARPI plus ADT, or monotherapy for ADT alone. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS:Overall survival (OS) and radiographic progression-free survival (rPFS) outcomes were collected. OS as primary endpoint, and rPFS as secondary endpoint, were analyzed separately in high- and low-volume patients. Additional subgroup analyses accounted for timing of metastases categorized as high-volume/synchronous, high-volume/metachronous, low-volume/synchronous, and low-volume/metachronous disease. EVIDENCE SYNTHESIS:Triplet combinations prolonged significantly OS and rPFS in high-volume disease (P-score 0.99), and high-volume/synchronous disease (P-score 0.99). ARPI/ADT doublets performed best in low-volume patients (P-score 0.94), and low-volume/metachronous (P-score 0.99). In the high-volume/metachronous population, triplets, and doublets were equally effective. CONCLUSIONS:The results provide collective evidence for treatment selection based on disease volume and timing of metastasis with strongest survival benefits of triplets for high-volume/synchronous mHSPC patients and of ARPI doublets for low-volume disease.

INTRODUCTION:Adjuvant immunotherapy has transformed the management of high-risk resected ccRCC, with pembrolizumab demonstrating improvements in DFS and OS. However, divergent outcomes across recent phase III trials highlight the limitations of clinicopathologic staging alone for guiding postoperative treatment decisions. A substantial proportion of patients may receive adjuvant therapy without deriving meaningful benefit, underscoring the urgent need for biologically informed risk stratification. AREAS COVERED:KIM-1, a circulating biomarker derived from proximal tubular epithelium, has emerged as a promising candidate in this setting. Elevated postoperative KIM-1 levels are consistently associated with inferior oncologic outcomes and may reflect minimal residual disease. Exploratory analyses from IMmotion010 suggest a potential predictive enrichment effect for adjuvant immunotherapy benefit in patients with high baseline KIM-1. Additional biomarkers including sarcomatoid differentiation, specific genomic drivers (PBRM1, BAP1, VHL), circulating tumor DNA, epigenetic signatures, and systemic inflammatory markers, provide complementary insights into tumor biology and host-tumor interaction. EXPERT OPINION:Although none of these biomarkers are currently validated for routine clinical decision-making, integrative models combining clinicopathologic and molecular features may enable more precise selection of patients for adjuvant immunotherapy and help reduce overtreatment in localized ccRCC.

BACKGROUND:Myositis may present as a treatment-related adverse event (TRAE) during immune checkpoint inhibitor (ICI) therapy. In the ARON-MOUSEION-017 meta-analysis, we aimed to assess the frequency of myositis among cancer patients treated with ICIs. RESEARCH DESIGN AND METHODS:The present systematic review and meta-analysis was registered in PROSPERO with ID no. CRD420261278193. Embase, PubMed, Scopus and Web of Science databases were consulted, using Boolean terms and keywords 'Immunotherapy,' 'Myositis' and 'Neoplasms.' RESULTS:For myositis of any grade, 13 studies were included, suggesting that heterogeneity across studies was high and statistically significant (p < 0.001; τ2 = 3.78; I2 = 95.3%, 95% CI [93.1%; 96.7%]), and the pooled proportion of patients affected by any-grade myositis treatment-related adverse events (TRAEs) was 4.2% (95% CI = [1.1%; 14.6%]). CONCLUSIONS:ICI-myositis often appears in concomitance with other immune-mediated conditions, such as myocarditis and myasthenia gravis. These events are clinically relevant, since they are often associated with more severe disease courses and unfavorable outcomes, increasing morbidity and mortality.

BACKGROUND:Enfortumab vedotin (EV) has transformed treatment for advanced urothelial carcinoma (aUC), but outcomes vary. Machine learning (ML) with explainable artificial intelligence (XAI) may improve survival prediction. METHODS:Data from 544 aUC patients receiving EV after platinum chemotherapy and immunotherapy (51 centers, 24 countries) were analyzed. Four machine learning (ML) algorithms (Random Survival Forest, XGBoost, Elastic Net-regularized Cox, Support Vector Machine) were trained (80%) and tested (20%) to predict overall survival (OS). SHapley Additive exPlanations (SHAP) analysis (on best performing ML model) provided interpretability. Performance was assessed by C-index and time-dependent area-under-the-curve (AUC). RESULTS:XGBoost (C-index 0.59) and Elastic Net (C-index 0.60) showed best discrimination. XGBoost achieved highest time-dependent AUCs (0.77, 0.87, 0.93 at 1, 2, 3 years). SHAP identified prior immunotherapy (pembrolizumab, atezolizumab/nivolumab), radiotherapy, and upper tract tumors with lower mortality risk; lung, liver, bone, soft tissue metastases increased risk. Eastern Cooperative Oncology Group performance status and metastatic distribution were key predictors. CONCLUSION:ML with XAI identifies clinically plausible survival predictors in EV-treated aUC. XGBoost and Elastic Net offer modest risk stratification, that are hypothesis generating but does not support routine clinical use. Functional status, metastatic pattern, and treatment context are key drivers, providing a foundation for externally validated prognostic tools.

Biochemical recurrence after definitive local therapy for prostate cancer represents a heterogeneous clinical state, with patients exhibiting short prostate-specific antigen (PSA) doubling time at particularly high risk of metastatic progression and cancer-related mortality. Persistent androgen receptor signaling plays a central role in sustaining occult micrometastatic disease, providing a strong biological rationale for early therapeutic intervention. The phase III EMBARK trial demonstrated that intensification of androgen receptor pathway inhibition with enzalutamide, administered either in combination with androgen deprivation therapy or as monotherapy, significantly improves metastasis-free survival and delays disease progression in patients with high-risk biochemical recurrence, with an overall survival benefit observed for combination therapy. Importantly, EMBARK introduced a PSA-guided treatment-suspension strategy designed to reduce cumulative treatment exposure. These findings redefine high-risk biochemical recurrence as an actionable disease state and support the integration of enzalutamide-based approaches into contemporary prostate cancer treatment algorithms.

10503 Background: Emerging evidence suggests that BRCA -altered prostate cancer (PC) is not a unique molecular subtype. However, the prognostic and therapeutic relevance of specific pathogenic/likely pathogenic variant (PV) in metastatic PC (mPC) remains poorly defined. We investigated the impact of BRCA2 PV type and position on clinical outcomes across across different metastatic settings. Methods: This international, hospital-based cohort study (Jan 2020–Apr 2025) included mPC patients (pts) across 29 centers who underwent germline, somatic, and/or ctDNA BRCA testing. Analysis included three settings: 1) mHSPC (ADT+docetaxel vs. ADT+ARPi); 2) mCRPC (ARPi vs. taxanes); 3) mCRPC treated with PARP inhibitors (PARPi). Outcomes [Time on Treatment (ToT); Overall Survival (OS)] were analyzed by PV type (frameshift, missense, nonsense, splicing; indels, SNV, CNV) and position: 1) Functional Domains (FDs) (RAD51-BD [AA 900-2000] vs. DBD [AA 2459-3190] vs. Others); 2) The recently identified Prostate Cancer Cluster Regions (PCCR) (c.756-c.1000 and 3' of c.7914 vs. Others). Results: Of 2.119 pts included, 401 harbored Homologous Recombination Repair PVs. In the cohort of 1.411 mHSPC pts, BRCA2 -mutated (n = 201) showed significantly shorter OS vs. wild-type (mOS 63 vs 76 months; HR 1.2, p = 0.02), regardless of first-line therapy. Contrary to previous reports, BRCA2 -mutated mHSPC pts had superior ToT from ADT+ARPi vs. ADT+docetaxel (55 vs 15 mos; HR 3.5, p < 0.001). Within the BRCA2 subgroup, PV location was highly prognostic for OS. In mHSPC, PCCR-outside variants (c.756-c.1000/3'of c.7914) and non-FD variants (RAD51-BD/DBD-outside) were associated with shorter OS (PCCR: 57 vs 97 mos, HR 4.0, p = 0.006; FD: 47 vs 88 mos, HR 3.0, p < 0.001). Similar prognostic impacts were confirmed in 684 mCRPC pts (PCCR: 78.0 vs 38.0 mos, HR 3.3, p = 0.01; FD: 64.0 vs 34.0 mos, HR 2.7; p = 0.009). Among 201 pts treated with olaparib, those with RAD51-BD PVs achieved significantly longer ToT (20.0 vs 7.0 mos; p = 0.01) and longer OS. Furthermore, frameshift deletions were associated with shorter OS compared to other PV types (15.9 vs 26.0 mos; p = 0.04). Conclusions: This is the largest longitudinal study to demonstrate that BRCA2 PV type and location are critical determinants of survival and treatment response in mPC. Our findings identify a "high-risk" molecular subgroup (PCCR and RAD51-BD/DBD-outside and frameshift deletions) with significantly poorer outcomes. These results provide a rationale for refined risk-stratification and personalized treatment selection, including early PARPi integration, in BRCA2 -mutated patients.

BACKGROUND:The therapeutic landscape of metastatic hormone-sensitive prostate cancer (mHSPC) has expanded significantly with triplet regimens, raising questions about their real-world applicability. This study evaluates the efficacy and safety of darolutamide- and abiraterone-based triplets using real-world data from the ARON-3 study. METHODS:A retrospective analysis was conducted on 247 mHSPC patients treated with DARO+DOCE+ADT or ABI+DOCE+ADT across 37 institutions in 14 countries. Key outcomes included progression-free survival (PFS), overall survival (OS), PSA kinetics, and safety. A propensity score was estimated based on key clinical variables and included as a covariate in Cox regression models to adjust for baseline imbalances between treatment groups. RESULTS:Data from 247 patients receiving triplet therapy were analyzed. The median OS for the entire cohort was not reached (NR). The median PFS was 24.8 months (95% CI: 18.7-33.6), with NR for DARO+DOCE+ADT and 21.5 months (95% CI: 13.1-25.2) for ABI+DOCE+ADT (P=0.007). In patients with visceral metastases, DARO+DOCE+ADT demonstrated superior outcomes, achieving higher OS rates at 6 months (97% vs. 83%, P=0.002) and 12 months (92% vs. 74%, P<0.001) compared to ABI+DOCE+ADT. The safety profiles of both regimens were comparable, although grade 3-4 fatigue was more frequently observed in the ABI+DOCE+ADT group. After adjusting for baseline imbalances through propensity score inclusion in multivariate models, the differences in OS (P=0.103) and PFS (P=0.135) between treatment groups did not reach statistical significance, although a numerical trend favoring DARO+DOCE+ADT was observed. CONCLUSIONS:Both regimens demonstrate efficacy, with DARO+DOCE+ADT offering superior outcomes in high-volume disease, especially visceral metastases. Nonetheless, the limited sample size and potential biases highlight the need for further follow-up and biomarker-driven studies in larger cohorts to refine treatment strategies.

BACKGROUND:Nowadays, systemic treatment with immune-based combinations for metastatic renal cell carcinoma (mRCC) is the gold standard. However, the benefit of these treatments in patients aged ≥70 years is uncertain. Thus, we evaluate the effectiveness and safety of first-line immune-based combinations in elderly patients with mRCC. METHODS:We retrospectively collected data from mRCC patients who were treated with immune-based combinations in first-line setting at 75 hospitals from 23 countries. Patients were assessed for overall survival (OS), overall response rate (ORR) and severe adverse events (SAEs). The statistical analysis encompassed the Fisher's Exact Test, the Kaplan-Meier methodology, the log-rank test, as well as univariate and multivariate Cox proportional hazards regression models. RESULTS:Of the 1990 mRCC patients included in this analysis, 739 patients were aged ≥70 years. Median OS was 41 months for patients aged <70 years and 30.1 months in patients aged ≥71 years (P<0.001). The age was a prognostic factor in both univariate and multivariate analysis. There was no difference in ORR (52% versus 44%, P=0.262). There was no statistical difference in incidence SAEs as well as dose reductions or treatment discontinuation between elderly and young patients. CONCLUSIONS:This large real-world study with mRCC patients substantiates the effectiveness and safety of first-line immune-based combination treatments in elderly patients. Nonetheless, this population has a lower survival in comparison to younger patients.

Background: Immune checkpoint inhibitors have revolutionized the treatment landscape for metastatic renal cell carcinoma (mRCC). However, some patients fail to experience durable benefits, especially those with bone metastases. Objective: This study aimed to evaluate the impact of bone-targeting agents (BTAs), specifically denosumab and zoledronic acid (ZA), on the clinical outcomes of patients with mRCC treated with nivolumab. Methods: This retrospective study analyzed data from the Meet-URO 15 trial on patients with mRCC who received nivolumab, categorizing them into BTA and non-BTA groups. Survival outcomes were assessed, with inverse probability of treatment weighting (IPTW) adjustment for confounding variables. Subsequently, the specific impact of different BTAs on the clinical outcomes was explored. Results: Of 203 mRCC patients with bone metastases, 38 received BTAs (BTA group) while 138 did not (non-BTA group). BTA treatment significantly improved the median progression-free survival (PFS) (291 vs. 117 days, p = 0.005) and overall survival (OS) (960 vs. 397 days, p = 0.008) compared with the non-BTA group, with a reduced risk of death (HR = 0.57, 95%CI = 0.34-0.95, p = 0.031) and progression or death (HR = 0.57, 95%CI = 0.35-0.92, p = 0.023) at multivariate analyses. IPTW adjustment confirmed these survival benefits, with a reduced risk of death (HR = 0.55-95%CI = 0.39-0.76, p < 0.001) and progression or death (HR = 0.58, 95%CI = 0.42-0.79, p < 0.001) in BTA patients. Furthermore, denosumab, compared with ZA and the non-BTA group, demonstrated superior OS (1,662 vs. 681 vs. 411 days, p < 0.001) and PFS (1,101 vs. 242 vs. 132 days, p < 0.001) in the same IPTW-adjusted population. Conclusion: This study suggests a potential beneficial impact of BTAs, especially denosumab, on the clinical outcomes after nivolumab therapy in mRCC patients with bone metastases. Prospective trials are needed to better define the impact of BTAs in these patients.

Background:Sex-based differences influence tumor biology, immune responses, and treatment outcomes in renal cell carcinoma (RCC), yet most computational models do not jointly incorporate sex hormones, immune composition, and tumor genetic evolution. Agent-based models (ABMs) effectively simulate tumor-immune interactions but are rarely extended to include sex-specific modulation or machine learning-based optimization. This study enhanced an agent-based learning model (ALM) to simulate RCC progression and treatment response by integrating hormonal effects, immune interactions, and tumor genetic adaptation with data-driven tuning. Methods:An RCC-specific ALM was developed incorporating immune agents (CD8+, NK, Treg, dendritic cells), hormone-sensitive mechanisms, tumor genetic modules, and effects of immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs). Tumor evolution was modeled using a genetic algorithm simulating promoter and gene mutations, with fitness defined by immune evasion and proliferation advantages. Model parameters were optimized using clinical outcomes from the ARON dataset via the Optuna framework, and performance was assessed using concordance index (CI) and mean squared error (MSE). Results:Simulations reproduced sex-specific treatment responses. Female models showed delayed initial responses but stronger late immune activation and rapid tumor regression, whereas male models exhibited more stable early responses but greater tumor resilience driven by genetic adaptations. Adaptive learning showed capability of reducing prediction error with both fitness functions. Conclusions:This ALM offers an exploratory framework to provide preliminary insights into how sex hormones, immune dynamics, and tumor genetics may jointly contribute to shaping RCC treatment outcomes. Although the limited sample size constrains validation, the results suggest the potential of combining ABMs with biological data-driven optimization to support patient prediction and call for further investigation in larger cohorts.

BACKGROUND:Outcomes of metastatic castration-resistant prostate cancer (mCRPC) treated with androgen receptor signaling inhibitors (ARSIs) vary widely and may not be fully reflected by PSA and standard clinicopathologic factors. We evaluated the prognostic value of serum neuron-specific enolase (NSE) at baseline and early on-treatment dynamics. METHODS:We retrospectively analyzed ARSI-treated mCRPC patients with available baseline NSE (n = 120). NSE was dichotomized by the upper limit of normal (ULN, 12.5 ng/mL). Radiographic progression-free survival (rPFS) and overall survival (OS) were estimated by Kaplan-Meier methods and compared by log-rank test. Multivariable Cox models adjusted for age, baseline PSA (per 100 ng/mL), line of therapy (2-4 vs 1), Gleason score (> 7 vs ≤ 7), metastatic timing (synchronous vs metachronous), and visceral metastases (present vs absent). NSE dynamics were evaluated using a 28-day landmark approach among patients alive and at risk at day 28 with available baseline and week-4 NSE (rPFS landmark n = 47; OS landmark n = 48); follow-up was redefined from day 28 and dynamics were modeled as log2(NSE4w/NSE0) (per doubling). RESULTS:Median follow-up was 44.7 months (95% CI 35.7-48.3). Baseline NSE > ULN was associated with shorter rPFS (9.4 vs 20.8 months) and OS (23.5 vs 38.2 months). In multivariable analyses, baseline NSE > ULN remained independently associated with inferior outcomes (rPFS HR 1.81, 95% CI 1.15-2.85, p = 0.011; OS HR 1.85, 95% CI 1.12-3.05, p = 0.017). In landmark models, higher NSE dynamics were independently associated with worse outcomes (rPFS HR 4.30, 95% CI 1.06-17.39, p = 0.041; OS HR 8.78, 95% CI 2.15-35.77, p = 0.002). CONCLUSIONS:In ARSI-treated mCRPC, baseline NSE above ULN and early 4-week NSE dynamics provide independent prognostic information for rPFS and OS, supporting NSE as a pragmatic adjunct to clinical risk stratification.

Background:Immune-based combination therapies have become the standard first-line treatment for metastatic renal cell carcinoma (mRCC) and have positively impacted survival outcomes in phase III clinical trials. However, these trials are conducted in highly selected populations and controlled settings, which may limit the generalizability of toxicity profiles to routine clinical practice. Real-world data are therefore essential to better characterize the incidence and determinants of severe adverse events (AEs) associated with immune-based combinations. Methods:We conducted a multinational, retrospective analysis of the ARON-1 registry, of patients with mRCC who received first-line immune-based combination therapy across 17 countries. The primary endpoint was to evaluate the real-world incidence of grade 3-4 (G3-G4) AEs. Logistic regression analyses were performed to identify clinical factors associated with toxicity. Overall survival (OS) was assessed using Kaplan-Meier methods, with landmark analyses to explore the association between G3-G4 AEs and survival outcomes. Results:Among 2, 401 patients receiving immune-based combinations, 1, 921 (80%) had complete data on grade 3-4 AEs and were included in the analysis. G3-G4 AEs occurred in 34% (n=653). Pembrolizumab plus lenvatinib was associated with the highest incidence of high-grade AEs, whereas nivolumab plus ipilimumab showed the lowest. Older age and female sex were independently associated with an increased risk of G3-G4 toxicity. Although the occurrence of severe AEs was associated with improved OS in unadjusted analyses, this association was non-significant in the 6-month landmark analyses. Conclusion:In this large, multinational real-world cohort, the incidence of G3-G4 adverse events in patients with mRCC treated with immune-based combinations was lower than that reported in pivotal clinical trials, underscoring meaningful differences between trial and routine practice settings. Patient- and regimen-specific factors significantly influenced toxicity risk. These findings highlight the complementary role of real-world evidence in informing toxicity management and support individualized treatment strategies to optimize outcomes in everyday clinical practice.

The MOUSEION-11 systematic review and meta-analysis aimed to assess the rates of asthenia in patients receiving immune checkpoint inhibitors (ICIs) compared with those who received non-immunotherapeutic regimens or placebo ones. The MOUSEION-11 was recorded with PROSPERO n. CRD420250654013 and carried out following the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). For any-grade asthenia, 39 studies were included. The pooled prevalence was 15.6

Systemic inflammatory indices have been proposed as prognostic biomarkers in several malignancies; however, their role in patients receiving avelumab maintenance for advanced urothelial carcinoma (aUC) remains poorly defined. This study aimed to evaluate the prognostic impact of inflammatory markers in this context and to develop a composite score for outcome stratification. We retrospectively analyzed patients with aUC who were treated with avelumab maintenance therapy. Systemic inflammatory markers - including the neutrophil-to-lymphocyte ratio (NLR), neutrophil-to-eosinophil ratio (NER), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), and the systemic immune-inflammation index (SII) - were collected at baseline and after treatment initiation (cycle 3), and changes from baseline to cycle three were analyzed (increase versus stability/decrease). Overall survival (OS), the primary endpoint, was evaluated using Kaplan-Meier and Cox models. A prognostic score was created from the multivariable analysis. Time-dependent Receiver operating characteristics (ROC) analysis was employed to evaluate model discrimination at 6, 12, and 24 months. The prognostic impact on disease control rate (DCR - secondary endpoint) was assessed using logistic regression and ROC curves. A total of 358 patients were included in the study. In the multivariable analysis, high NLR, high NER, low LMR, increasing NLR trend, bone and liver metastases were independently associated with worse OS. These variables were incorporated into a 0-6 point prognostic score, which demonstrated good discrimination (C-index 0.76; AUC at 6, 12, and 24 months: 0.87, 0.75, and 0.73, respectively). The score remained prognostic across subgroups and following sensitivity analyses. High LMR, low NER, the absence of liver metastases, and the absence of bone metastases were independently associated with higher DCR. A response-associated score combining these variables showed a decreasing DCR from 69% (score 0) to 25% (score 4). Baseline and dynamic inflammatory markers may serve as prognostic factors for OS in patients with aUC undergoing avelumab maintenance therapy. A composite score that integrates laboratory and clinical features could allow for clinically meaningful stratification of survival and response outcomes, with potential applications in clinical practice. However, a prospective evaluation is necessary.