681 Background: The therapeutic landscape of metastatic Urothelial Carcinoma (mUC) is rapidly evolving, alongside increasing opportunities to analyze molecular alteration and molecular classification. FGFR alteration (FGFRa) occur in about 15-20% of mUC patients. Data from randomized-controlled THOR trial demonstrated the clinical efficacy of erdafitinib, an FGFR 1-4inhibitor, in pretreated FGFR3/2a mUC. So, real-world data (RWD) on FGFRa patients remain an unmet need. Methods: SATURNO (NCT06235268) is an Italian, multicenter, prospective, non-interventional study enrolling all mUC patients managed at the participant institutions from Nov 2023 to Sept 2025. The Web National Registry includes patients with metastatic disease or with nodal involvement not suitable to surgery. Participating institutions were selected to adequately represent different geographical area. Results: A total of 237 patients were tested for FGFRa. Among them, 171 (72%) were FGFR3/2a and 66 (28%) were FGFR wild-type (WT). In the FGFR3/2a group, 134/171 (78%) were male and 37/171 (22%) were female; 165/171 (96%) had pure urothelial carcinoma histology. The most common metastatic sites were lung (61/171, 35%), liver (21/171, 12%), bone (41/171, 24%), and retroperitoneal lymph nodes (50/171, 29%). Compared with FGFR WT patients, older age was significantly associated with FGFR3/2a (OR 1.05, 95% CI 1.02–1.09, p = 0.003). Retroperitoneal lymph node involvement was less frequent among FGFR3/2a patients (29% vs 44%, OR 0.53, 95% CI 0.29–0.95, p = 0.033). FGFR3/2a tended to be more common in upper tract urothelial carcinomas (UTUC) compared with bladder tumors (23.4% vs 12.1%, OR 2.12, 95% CI 0.98–5.15, p = 0.073). FGFR3/2a patients were less likely to receive maintenance therapy (OR 0.36, 95% CI 0.19–0.65, p < 0.001). Among patients treated with platinum-based combinations (91/171, 53%), 41/91 (45%) FGFR3a patients received avelumab maintenance compared to 31/58 (53%) in the FGFR WT subgroup. Additionally, 26/91 (29%) FGFR3a patients had primary refractory disease to platinum-based therapy, compared with 14/58 (24%) among FGFR WT patients. Conclusions: RWD from this prospective registry show that FGFR3/2a is more common in older patients and, consistent with previous reports, tends to occur more frequently in UTUC. Retroperitoneal nodal involvement, usually associated with better prognosis, is less common in FGFR3/2a. FGFR3/2a are less likely to receive avelumab maintenance therapy due to primary progression to platinum-based combination. Acknowledgments: The IT infrastructure on which the urothelial tumor registry is based was developed thanks to the unconditional support of Gilead Sciences. Clinical trial information: NCT06235268 .

Introduction Bone metastases (BMs) in patients with metastatic renal cell carcinoma (mRCC) negatively affect survival, quality of life, and increase the risk of skeletal-related events (SREs). Evidence remains limited in the era of first-line immune-based combinations. Patients and methods Meet-URO 33 is an Italian multicenter observational retrospective–prospective study enrolling mRCC patients receiving first-line therapy. The primary endpoint was overall survival (OS). Secondary endpoints included progression-free survival (PFS), clinical characterization, incidence of SREs, and impact of bone-targeting agents (BTAs). Survival was analyzed using the Kaplan–Meier method, log-rank test and Cox proportional hazards model. Results A total of 1696 patients enrolled between 2021 and 2025 were included; 526 (31%) had BMs at metastatic diagnosis. Patients with BMs more frequently had poorer performance status and unfavorable IMDC risk. The presence of BMs was associated with significantly worse OS (median 26.9 vs 102.1 months; HR 0.53, p<0.001) and worse PFS (median 14.2 vs 19.4 months; HR 0.71, p<0.001), with OS and PFS varying according to first-line regimen. Worse OS persisted across IMDC risk classes and treatment types; PFS differences were not significant in favorable/intermediate IMDC risk groups and with TKI monotherapy. Neither anatomical site nor number of BMs significantly affected OS. SRE incidence in patients with BMs was 26.8%, more frequent with spinal, rib, or other-site involvement, and more common in BTA-treated patients (22.2% vs 13.7%, p = 0.03), likely reflecting selection bias. Conclusions BMs are confirmed a negative prognostic factor in mRCC involving persistent unmet clinical needs.

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.

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.

Background Immune checkpoint inhibitor doublet (ICI–ICI) and ICI plus tyrosine kinase inhibitor (ICI–TKI) regimens are the cornerstone of treatment for metastatic renal cell carcinoma (mRCC), although no head-to-head comparisons are currently available. This study aimed to compare the real-world effectiveness of ICI-ICI vs ICI-TKI combinations in patients with intermediate- and poor-risk mRCC according to International Metastatic RCC Database Consortium (IMDC). Methods The Meet-URO 33 study is a multicentre retrospective-prospective registry collecting real-world data on patients with mRCC. Multivariable logistic and Cox models were built for objective response rate (ORR), PFS and OS, with a propensity score (PS) adjustment for baseline imbalances. Results Among 1497 patients, 755 were intermediate-risk (199 ICI-ICI, 556 ICI-TKI) and 312 poor-risk (77 ICI-ICI, 212 ICI-TKI). Median follow-up was 14.2 months (8.0 months and 14.5 months in poor- and intermediate-risk subgroups, respectively). In poor-risk patients, median OS was 20.3 vs 12.9 months (HR 0.87, 95% CI: 0.59–1.28, p = 0.49), and median PFS was 6.7 vs 8.7 months (HR 1.10, 95% CI: 0.79–1.54, p = 0.53), for ICI–ICI vs ICI–TKI, respectively. In the intermediate-risk patients treated with ICI-ICI vs ICI-TKI, median OS was 37.8 vs 35.5 months (HR: 1.08; 95% CI: 0.77–1.50; p = 0.65), and median PFS was 17.8 vs 18.6 months (HR 1.29, 95% CI: 1.00–1.66, p = 0.050). ORR was 42.9% vs 45.8% in poor-risk patients (OR 0.72, 95% CI: 0.39–1.34, p = 0.303) and 48.1% vs 54.3% in intermediate-risk patients (OR 0.71, 95% CI: 0.48–1.04, p = 0.075). Conclusions No statistically significant differences in survival or response were observed between ICI-ICI and ICI-TKI combinations in patients with IMDC intermediate- and poor-risk mRCC.

Background: Despite the availability of several first-line (1L) systemic therapies for metastatic renal cell carcinoma (mRCC), no validated biomarkers currently guide the selection of 1L systemic treatment. Objectives: To identify baseline clinical features associated with 1L treatment selection in a large real-world mRCC population. Design: Meet-URO 33–REGAL is a multicenter study with prospective and retrospective components, enrolling patients with mRCC receiving 1L systemic therapy since January 2021. Methods: Baseline patient and disease characteristics were analyzed to compare treatment selection among dual immune checkpoint inhibitor therapy (ICI–ICI), ICI plus tyrosine kinase inhibitor combinations (ICI–TKI), and TKI monotherapy. Multivariable logistic regression models were used to evaluate clinical features associated with pairwise treatment selection. Results: A total of 1695 patients from 58 centers were included: 248 (14.6%) received TKI monotherapy, 338 (20.0%) ICI–ICI, and 1109 (65.4%) ICI–TKI. ICI–ICI was more commonly selected in patients with sarcomatoid features (14.5% vs 7.4% for ICI–TKI, p < 0.001) and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) intermediate/poor-risk disease (92.0% vs 80.1%, p < 0.001). In multivariable analysis, compared with TKI monotherapy, ICI–TKI selection was associated with IMDC intermediate-risk disease (odds ratio (OR) 2.16, 95% confidence interval (CI) 1.25–3.74, p = 0.006), poor-risk disease (OR 2.89, 95% CI 1.38–6.06, p = 0.005), and bone metastases (OR 1.79, 95% CI 1.29–2.49, p = 0.001). In regimen-specific comparisons, nivolumab plus cabozantinib was associated with bone metastases and non-clear cell histology; pembrolizumab plus lenvatinib with eastern cooperative oncology group (ECOG) performance status 0 and pancreatic involvement; and nivolumab plus ipilimumab with cardiovascular and metabolic comorbidities and lymph node metastases. TKI monotherapy was more commonly selected in older patients and those with comorbidities, consistent with a more selected clinical phenotype in routine clinical practice. Conclusion: Meet-URO 33 provides a real-world snapshot of 1L decision-making in mRCC. Distinct clinical patterns, including histology, metastatic sites, performance status, comorbidities, and prognostic risk, were associated with treatment selection. These findings characterize clinical phenotypes in routine practice and provide context for future effectiveness, safety, and treatment-sequencing analyses of 1L therapeutic strategies within the Meet-URO 33 cohort over time.

e16572 Background: Avelumab maintenance after first-line platinum-based chemotherapy represents a cornerstone for the treatment of metastatic urothelial carcinoma (mUC). However, identifying prognostic biomarkers is paramount for optimizing patients’ benefits while minimizing toxicity. Systemic inflammatory indexes have been studied as prognostic biomarkers for immune checkpoint inhibitors in many tumor types, but their role in mUC is still debatable. We hypothesized that systemic inflammatory indexes could be correlated with survival in mUC patients treated with maintenance avelumab. Methods: Meet-URO25 is a multicenter Italian prospective/retrospective registry of mUC patients treated with first-line avelumab maintenance from 01/2021 to 12/2024. In the SAILOR/Meet-URO25a sub-analysis, we investigated the correlation with overall survival (OS) of five inflammatory indexes (neutrophil-to-lymphocyte ratio [NLR], lymphocyte-to-monocyte ratio [LMR], platelet-to-lymphocyte ratio [PLR], neutrophil-to-eosinophil ratio [NLR], and systemic-inflammation-index [SII]) at baseline and after 3 cycles of avelumab. ROC curves with Youden’s test, the Kaplan-Meier method with log-rank test, and Cox regression analyses were used. Results: 258 patients (106 female; median age: 63yrs) were included in the analysis. Low baseline NLR (Hazard ratio [HR] 0.37; 95% confidence interval [CI] 0.19-0.73; p: 0.016) and SII (HR 0.75; 95%CI 0.52-0.98; p: 0.033) were associated with better OS. After 3 cycles of therapy, decreasing NLR (HR 0.64; 95%CI 0.43-0.94; p: 0.02), NER (HR 0.67; 95%CI 0.46-0.99; p: 0.006) and SII (HR 0.55; 95%CI 0.37-0.81; p: 0.002) were significantly associated with longer OS. In the multivariate analysis, the presence of liver metastases, response both to first-line chemotherapy and avelumab, baseline NLR, early NLR and NER reduction were independent predictors of OS. Conclusions: Our results suggest that baseline levels of NLR and systemic inflammatory indexes and their kinetics after avelumab initiation may be prognostic in pts with mUC. The combined evaluation of systemic inflammatory indexes and their early changes should be further investigated to obtain additional prognostic or predictive value.

The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is a widely used prognostic model for metastatic renal cell carcinoma (mRCC). Few studies have used IMDC as a prognostic tool for subsequent lines. In our analysis, we showed that IMDC modifications can exert a prognostic role for nivolumab in pre-treated mRCC patients. Further investigations should be conducted with the newest immunotherapy-based combinations and sequencing strategies. Introduction: The International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score is the most important prognostic score to stratify patients with metastatic renal cell carcinoma (mRCC), helping to guide treatment choice in first line. We hypothesized that IMDC change may also exert a prognostic role in subsequent lines of mRCC therapy. Methods: Meet-URO 15 is a multicenter Italian study of patients with mRCC receiving nivolumab as a second or subsequent line of therapy. This posthoc analysis aimed to evaluate the overall survival (OS) and progression- free survival (PFS) from nivolumab start as primary endpoints, overall response rate (ORR) and disease-control rate (DCR) as secondary endpoints, according to the change in the IMDC category from the first-line setting (baseline) to nivolumab start. Patients with available prognostic IMDC category information at baseline and before nivolumab were included. Results: 492 patients were included in the analysis. At baseline, 165 (33.5%), 287 (58.3%), and 40 patients (8.2%) had favorable, intermediate, and poor IMDC categories, respectively. Before nivolumab, 364 patients (73.9%) remained in the same prognostic category as at baseline, 27 (5.5%) improved, and 101 (20.5%) deteriorated. Significantly longer mPFS ( P = .01) and mOS ( P < .01) were reached by patients with a stable favorable group compared to those worsening to intermediate/poor. A longer mOS was also achieved from intermediate/poor patients who improved their IMDC category before nivolumab compared to those remaining stable/worsening ( P < .01 and P = .04, respectively). Maintaining IMDC category stability from baseline to nivolumab determined a more consistent DCR in favorable patients ( P = .03). Overall, patients who improved their IMDC risk score reached better survival outcomes than those who remained stable/deteriorated. Conclusions: In our sub-analysis, the shift in the IMDC risk category appears to be a helpful prognostic tool for assessing the outcomes of patients with mRCC treated with >= 2nd line nivolumab.

BackgroundImmunotherapies exhibit peculiar cancer response patterns in contrast to chemotherapy and targeted therapy. Some patients experience disease response after initial progression or durable responses after treatment interruption. In clinical practice, immune checkpoint inhibitors may be continued after radiological progression if clinical benefit is observed. As a result, estimating progression-free survival (PFS) based on the first disease progression may not accurately reflect the actual benefit of immunotherapy.MethodsThe Meet-URO 15 study was a multicenter retrospective analysis of 571 pretreated metastatic renal cell carcinoma (mRCC) patients receiving nivolumab. Time to strategy failure (TSF) was defined as the interval from the start of immunotherapy to definitive disease progression or death. This post-hoc analysis compared TSF to PFS and assess the response and survival outcomes between patients treatated beyond progression (TBP) and non-TBP. Moreover, we evaluated the prognostic accuracy of the Meet-URO score versus the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) score based on TSF and PFS.ResultsOverall, 571 mRCC patients were included in the analysis. Median TSF was 8.6 months (95% CI: 7.0 – 10.1), while mPFS was 7.0 months (95% CI: 5.7 – 8.5). TBP patients (N = 93) had significantly longer TSF (16.3 vs 5.5 months; p < 0.001) and overall survival (OS) (34.8 vs 17.9 months; p < 0.001) but similar PFS compared to non-TBP patients. In TBP patients, a median delay of 9.6 months (range: 6.7-16.3) from the first to the definitive disease progression was observed, whereas non-TBP patients had overlapped median TSF and PFS (5.5 months). Moreover, TBP patients had a trend toward a higher overall response rate (33.3% vs 24.3%; p = 0.075) and disease control rate (61.3% vs 55.5%; p = 0.31). Finally, in the whole population the Meet-URO score outperformed the IMDC score in predicting both TSF (c-index: 0.63 vs 0.59) and PFS (0.62 vs 0.59).ConclusionWe found a 2-month difference between mTSF and mPFS in mRCC patients receiving nivolumab. However, TBP patients had better outcomes, including significantly longer TSF and OS than non-TBP patients. The Meet-URO score is a reliable predictor of TSF and PFS.

Introduction: Penile squamous cell carcinoma (PSCC) is a rare tumor with an aggressive behavior. The Meet-URO 23/I-RARE registry includes rare genitourinary malignancies. We extracted patients with PSCC to conduct a retrospective study aimed at assessing clinical outcomes and prognostic factors.Patients and Methods: Primary endpoints were overall survival and progression-free survival. Prognostic factors for OS and PFS were analyzed using univariate and multivariate analysis.From the Meet-URO 23/I-RARE database, we extracted 128 patients with diagnosis of PSCC. 48% of patients underwent first-line of therapy.Results: In the overall population, median OS from diagnosis was 34.6 months. Significant differences in median OS were observed according to ECOG PS at diagnosis (57.3 months vs 8.3 months; p < 0.001), and median age (≤ 77y 88.8 months vs > 77y 26 months; p = 0.013). At multivariate analysis, ECOG PS 2-4 at diagnosis (HR 3.04) and lymph node metastases (HR 2.49) were independently associated with a higher risk of death.Among patients undergoing first-line therapy (n = 61), median OS was 12.3 months, and a statistically significant difference was found according to type of response to first-line (DCR 24.4 months vs PD 7.1 months; p < 0.001). Multivariate analysis showed that only age > 77 years was associated with a worse OS (HR 2.16). A statistically significant difference in PFS was found according to platinum plus 5-fluorouracil vs platinum plus taxane (4.9 vs 3.4 months; p = 0.036) and regimens with two vs three drugs (3.4 vs 8.6 months; p = 0.019). At the multivariate analysis only regimens with platinum plus taxane were associated with worse PFS (HR 2.83).Conclusion: In our registry study, PSCC is confirmed to be an aggressive disease. Poor ECOG PS, presence of lymph node metastases, and higher age at diagnosis appear to be associated with worse survival outcomes.

Introduction: The Meet-URO 18 study is a multicentric study of patients with metastatic renal cell carcinoma receiving nivolumab in the second-line and beyond, categorized as responders (progression-free survival ≥ 12 months) and non-responders (progression-free survival < 3 months). Areas covered: The current study includes extensive immunohistochemical analysis of T-lineage markers (CD3, CD4, CD8, CD8/CD4 ratio), macrophages (CD68), ph-mTOR, CD15 and CD56 expression on tumor cells, and PD-L1 expression, on an increased sample size including 161 tumor samples (113 patients) compared with preliminary presented data. Responders' tumor tissue (n = 90; 55.9%) was associated with lower CD4 expression (p = 0.014), higher CD56 expression (p = 0.046) and higher CD8/CD4 ratio (p = 0.030). Expert opinion/commentary: The present work suggests the regulatory role of a subpopulation of T cells on antitumor response and identifies CD56 as a putative biomarker of immunotherapy efficacy.

BackgroundImmune-checkpoint inhibitors (ICIs) have significantly improved metastatic renal cell carcinoma (mRCC) prognosis, although their efficacy in patients with bone metastases (BMs) remains poorly understood. We investigated the prognostic role of natremia in pretreated RCC patients with BMs receiving immunotherapy.Materials and methodsThis retrospective multicenter study included RCC patients with BMs receiving nivolumab as second-line therapy or beyond. Inclusion criteria involved baseline sodium levels (pre-ICI) and sodium levels after 4 weeks of nivolumab initiation (post-ICI). The population was divided into two groups based on the median value, and response rates, progression-free survival (PFS), and overall survival (OS) were assessed.ResultsAmong 120 eligible patients, those with pre-treatment sodium levels ≥140 mEq/L showed longer OS (18.7 vs. 12.0 months, p=0.04). Pre-treatment sodium levels ≥140 mEq/L were associated with better OS compared to levels <140 mE/L (18.7 vs. 12.0, p=0.04). Post-treatment sodium levels ≥140 mEq/L were associated with improved PFS (9.6 vs. 3.2 months) and OS (25.1 vs. 8.8 months) (p=0.05 and p<0.01, respectively). Patients with consistent sodium levels ≥140 mEq/L at both time points exhibited the best outcomes compared to those with lower values (PFS 11.5 vs. 3.3 months and OS 42.2 vs. 9.0 months, respectively, p<0.01). Disease control rate was significantly higher in the latter group (p<0.01). Multivariate analysis confirmed the prognostic significance of sodium levels.ConclusionElevated sodium levels (≥140 mEq/L) pre- and post-ICI treatment correlate with better survival outcomes in mRCC patients with BMs. This finding suggests sodium level assessment as a potential prognostic factor in these patients and warrants further investigation, particularly in combination immunotherapy settings.

INTRODUCTION:Rare genitourinary tumors are lacking of randomized and observational data. We aimed to describe the clinical characteristics and outcomes of patients with collecting duct carcinoma (CDC) through the Meet-URO 23/I-RARE database. MATERIALS AND METHODS:We performed a multicentric retrospective-prospective study within the Meet-URO network, enrolling patients from March 2021 (retrospectively up from 2011) until March 2023. The primary objective was to describe the clinical characteristics of patients with CDC, the secondary objectives were to assess the oncological outcomes in terms of relapse-free survival (RFS), progression-free survival (PFS), overall survival (OS) and objective response rate (ORR) to treatment. RESULTS:37 patients with CDC were enrolled. Four patients underwent only surgery, 33 received first-line systemic therapy. Median OS was 22.1 months (95% CI, 8.9-31.9). Median RFS for patients with localized disease at onset (n = 30) was 3.7 months (95% CI, 1.9-12.8), median PFS for first-line treatment was 3.3 months (95% CI, 2.7-9.9), with an ORR of 27%. Female sex and good performance status (PS) were associated with longer PFS (P = .072 and P < .01, respectively) and OS (P = .030 and P = .141, respectively). CONCLUSIONS:Patients with CDC had dismal prognosis, with scarce benefit from the available treatments. Female sex and good PS seemed to be associated with better prognosis.

158 Background: ECHOS trial is a large real-world study, which is collecting data on mCSPC patients treated in the daily clinical practice in Italy from 2015. To date, > 1500 pts were included in the study, most of them treated with DOC, according to the availability of the active agents over the time in Italy. In the present analysis, we assessed the characteristics and outcomes of mCSPC pts progressing within 6 mos from the start of DOC. Methods: We retrospectively and prospectively reviewed the clinical records of a consecutive series of mCSPC pts treated with DOC in the daily clinical practice in 69 Italian Hospitals. The treatment mostly consisted of DOC at the standard dose of 75 mg/sqm every 3 wks for six courses. For each pt we recorded the pre and post-DOC clinical history, the baseline characteristics of the pts, the treatment details and clinical outcomes. For the purpose of the present study, we considered only pts who ended chemotherapy by September 2022. PR was defined as the onset of progressive disease within 6 mos from the DOC start. Results: Among 920 mCSPC pts treated with DOC, 122 (14.3%) were PR. Most of them (95.6%) presented a de novo (DN) disease, which showed mostly high volume (HV) features (82.3%). Compared to the pts without PR, those showing PR presented more frequently a visceral involvement (26.2% vs 18.2%; p = 0.038), had lower baseline levels of hemoglobin (12.8 g/dl vs 13.4 g/dl; p < 0.0001), and higher baseline levels of lactate dehydrogenase (266 U/L vs 220,5 U/L; p < 0.002). No other significant differences were observed in terms of baseline PSA and alkaline phosphatase levels, symptoms degree, disease volume and timing of mets presentation between PR e no-PR pts. The median number of life prolonging agents administered after DOC progression was 1 in pts with PR as well as in pts without PR. The median overall survival was 11.9 mos and 44.9 mos in PR and no-PR pts, respectively (p < 0.0001). Conclusions: Our data suggest that PR led a significant worsening of prognosis with a relevant shortening of life expectancy in pts who receive DOC for mCSPC.

Aim: To define the prognostic significance of first-line TKI in mRCC patients receiving nivolumab.Materials and methods: A total of 571 mRCC patients who received >= second line nivolumab were included in this subanalysis. The correlation between prior TKI (sunitinib vs. pazopanib) and overall response rate (ORR), disease control rate, progression-free survival and overall survival were investigated. Additionally, the impact of TKI choice according to the International Metastatic RCC Database Consortium prognostic score was examined.Results: There was no significant difference between sunitinib and pazopanib groups in terms of mPFS, mOS, overall response rate and disease control rate. Moreover, no difference between sunitinib and pazopanib was found according to the International Metastatic RCC Database Consortium prognostic score.Conclusion: There is no conclusive evidence favoring pazopanib or sunitinib treatment before initiating nivolumab therapy in metastatic renal cell carcinoma patients. Article highlightsIntroductionTKI monotherapy is still an option for mRCC patientsDespite the success of immune-checkpoint inhibitors, TKI monotherapy remains an option for selected mRCC patients, particularly those with favorable-risk IMDC status or those unsuitable for immunotherapy.In vitro studies have indicated that pazopanib exhibits stronger immunomodulatory activity compared with sunitinib.In clinical practice there are no established criteria for selecting the first-line TKI and the optimal treatment sequence remains uncertain.Material & methodsThis study included patients with mRCC who had progressed after prior treatment with sunitinib or pazopanib and received 2nd or further line nivolumab in a real-world setting.This subanalysis of the Meet-URO 15 study aims to investigate survival (OS, PFS) and response outcomes (ORR, DCR).ResultsThere was no significant difference between previous sunitinib or pazopanib in terms of mPFS, mOS, ORR and DCR.No difference between previous sunitinib and pazopanib was found according to the IMDC prognostic score.There is no conclusive evidence favoring pazopanib or sunitinib treatment before initiating nivolumab therapy in mRCC patients.DiscussionFuture challengesUnderstanding the interactions between immunotherapy, the immune system, and specific types of TKIs remains a relevant topic in both clinical trials and clinical practice.More evidence is needed to better understand the differences among currently available immuno-combinations.Further studies are necessary to gain a better understanding of the optimal treatment selection and sequence.

Although nivolumab prolongs overall survival (OS) in pretreated patients with metastatic renal cell carcinoma (mRCC), underlining clinical and biological features of long-term responses are still to be determined. This study aims to investigate clinical and pathological characteristics of mRCC patients who achieved long-term responses during nivolumab treatment. A retrospective analysis was performed on mRCC patients receiving nivolumab as second or further therapy line between May 2016 and January 2019 in 34 Italian Oncology Centres. Outcome assessments and logistic regression were performed to evaluate factors influencing long-term responses. A total of 571 patients with a median age of 61 years (range 17–85) were included in the analysis. With a median follow-up of 22.1 (1.0–89.0) months, 23.1

Importance Low sodium levels have been associated with negative outcomes among patients with metastatic renal cell carcinoma (mRCC) receiving therapies other than immune checkpoint inhibitors (ICIs).Objective To investigate the role of natremia in patients with mRCC receiving nivolumab as a second-line or subsequent therapy.Design, Setting, and Participants In this retrospective cohort study, the clinical and biochemical data of patients with mRCC receiving nivolumab were collected from October 2015 to November 2019 as part of a multicenter Italian study. Data analysis was performed from February to March 2023.Exposure Nivolumab was administered intravenously at a dose of 3 mg/kg every 2 weeks and, since May 2018, at a fixed dose of 240 mg every 2 weeks or 480 mg every 4 weeks. Patients were divided into 2 groups according to their median serum sodium value (<140 or >= 140 mEq/L).Main Outcomes and Measures The primary outcomes were the associations of pre-ICI and post-ICI sodium levels with overall survival (OS), progression-free survival (PFS), objective response rate, and disease control rate (DCR). The Kaplan-Meier method was used to estimate PFS and OS, and differences between groups were compared using the log-rank test.Results A total of 401 patients with mRCC receiving nivolumab as second-line therapy were evaluated, and 355 eligible patients (median [range] age, 76 [44-84] years; 258 male patients [72.7%]) were included in the final cohort. Among patients with pre-ICI sodium greater than or equal to 140 mEq/L compared with those with sodium less than 140 mEq/L, the median PFS was 9.3 months (95% CI, 6.5-11.5 months) vs 7.4 months (95% CI, 4.6-10.1 months; P = .90), and the median OS was 29.2 months (95% CI, 21.8-35.9 months) vs 20.0 months (95% CI, 14.1-26.8 months; P = .03). Patients with post-ICI sodium values greater than or equal to 140 mEq/L had longer PFS (11.1 months [95% CI, 8.5-1.5 months] vs 5.1 months [95% CI, 4.1-7.5 months]; P = .01) and OS (32.9 months [95% CI, 25.1-42.6 months] vs 17.1 months [95% CI, 12.6-24.5 months]; P = .006) compared with patients with sodium values less than 140 mEq/L. Patients with both pre-ICI and post-ICI sodium values greater than or equal to 140 mEq/L exhibited a significant improvement in clinical outcomes compared with those with a value less than 140 mEq/L (PFS, 11.5 months [95% CI, 8.8-16.4 months] vs 5.8 months [95% CI, 4.4-8.3 months]; P = .008); OS, 37.6 months [95% CI, 29.0-49.9 months] vs 19.4 months [95% CI, 14.1-24.5 months]; P = .01). Moreover, sodium levels greater than or equal to 140 mEq/L were associated with significantly better DCR than lower sodium levels.Conclusions and Relevance In this retrospective cohort study of patients with mRCC receiving nivolumab, sodium values greater than or equal to 140 mEq/L, both before and/or after ICI, were associated with better OS and PFS, as well as a higher DCR, compared with levels less than 140 mEq/L. These findings suggest that sodium levels may be associated with survival outcomes in patients with mRCC and may have potential use as variables to consider in patients' risk scores.

Non-clear cell renal cell carcinoma (nccRCC) represents a heterogeneous histological group which is 20–25% of those with renal cell carcinoma (RCC). Patients with nccRCC have limited therapeutic options due to their exclusion from phase III randomized trials. The aim of the present study was to investigate the effectiveness and tolerability of pembrolizumabaxitinib combination in chromophobe and papillary metastatic RCC (mRCC) patients enrolled in the I-RARE (Italian Registry on rAre genitor-uRinary nEoplasms) observational ongoing study (Meet-URO 23). Baseline characteristics, objective response rate (ORR), disease control rate (DCR) and progression-free survival (PFS) and toxicities were retrospectively and prospectively collected from nccRCC patients treated in 14 Italian referral centers adhering to the Meet-Uro group, from December 2020 to April 2022. Only patients with chromophobe and papillary histology were considered eligible for the present pre-specified analysis. There were 32 eligible patients who received pembrolizumab-axitinib as first-line treatment, of whom 13 (40%) had chromophobe histology and 19 (60%) were classified as papillary RCC. The DCR was 78.1% whereas ORR was 43.7% (11 patients achieved stable disease and 14 patients obtained partial response: 9/19 papillary, 5/13 chromophobe). Six patients (18.7%) were primary refractory. Median PFS was 10.8 months (95%CI 1.7–11.5). Eleven patients (34.3%) interrupted the full treatment due to immune-related adverse events (irAEs): G3 hepatitis (n = 5), G3 hypophisitis (n = 1), G3 diarrhea (n = 1), G3 pancreatitis (n = 1), G3 asthenia (n = 1). Twelve patients (37.5%) temporarily interrupted axitinib only due to persistent G2 hand-foot syndrome or G2 hypertension. Pembrolizumab-axitinib combination could be an active and feasible first-line treatment option for patients with papillary or chromophobe mRCC.

Background: Prognostic and predictive factors for patients with metastatic renal cell carcinoma (mRCC) treated with immunotherapy are highly warranted, and the immune tumor microenvironment (I-TME) is under investigation. Methods: The Meet-URO 18 was a multicentric retrospective study assessing the I-TME in mRCC patients treated with ≥2nd-line nivolumab, dichotomized into responders and non-responders according to progression-free survival (≥12 months and ≤3 months, respectively). The primary objective was to identify differential immunohistochemical (IHC) patterns between the two groups. Lymphocyte infiltration and the expressions of different proteins on tumor cells (CD56, CD15, CD68, and ph-mTOR) were analyzed. The expression of PD-L1 was also assessed. Results: A total of 116 tumor tissue samples from 84 patients (59% were primary tumors and 41% were metastases) were evaluated. Samples from responders (N = 55) were significantly associated with lower expression of CD4+ T lymphocytes and higher levels of ph-mTOR and CD56+ compared with samples from non-responders (N = 61). Responders also showed a higher CD3+ expression (p = 0.059) and CD8+/CD4+ ratio (p = 0.084). Non-responders were significantly associated with a higher percentage of clear cell histology and grading. Conclusions: Differential IHC patterns between the tumors in patients who were responders and non-responders to nivolumab were identified. Further investigation with genomic analyses is planned.

Background: Information on immune responses in cancer patients following mRNA COVID-19 vaccines is still insufficient, but generally, patients had impaired serological responses, especially those with hematological malignancies. We evaluated serological response to COVID-19 mRNA vaccine in cancer patients receiving chemotherapy compared with healthy controls. Methods: In total, 195 cancer patients and 400 randomly selected controls who had been administered a Pfizer-BioNTech or Moderna COVID-19 vaccines in two doses were compared. The threshold of positivity was 4.33 BAU/mL. Patients were receiving anticancer treatment after the first and second dose of the vaccines. Results: a TOTAL OF 169 patients (87%) had solid tumors and 26 hemolymphopoietic diseases. Seropositivity rate was lower in patients than controls (91% vs. 96%), with an age/gender-adjusted rate ratio (RR) of 0.95 (95% CL = 0.89–1.02). Positivity was found in 97% of solid cancers and in 50% of hemolymphopoietic tumors. Both advanced and adjuvant therapy seemed to slightly reduce seropositivity rates in patients when compared to controls (RR = 0.97, 95% CL = 0.89–1.06; RR = 0.94, 95% CL = 0.87–1.01). Conclusions: the response to vaccination is similar in patients affected by solid tumors to controls. On the contrary, hemolymphopietic patients show a much lower response than controls.