Despite many treatment strategies available for metastatic renal cell carcinoma (mRCC), predictive biomarkers of response to immunotherapy are still needed. In this context, growing efforts have been devoted to translational research, especially focusing on the immune tumor microenvironment (I-TME). The Meet-URO 18 is a multicentric retrospective study assessing the I-TME of mRCC patients receiving ≥ 2nd line nivolumab, divided into responders and non-responders according to clinical benefit [progression-free survival ≥ 12 and ≤ 3 months]. The primary objective was to identify differential immunohistochemical and molecular patterns between the two groups. We present the transcriptomic analysis performed on primary tumor tissues using a custom NanoString panel of 66 genes from the D’Costa et al. signature, grouped into angiogenesis, T-effector response, tumor invasion, and calcium signaling. Forty-two samples (25 responders and 17 non-responders) underwent transcriptomic analysis using the NanoString 66-gene immune-oncology panel. Hierarchical clustering recapitulated the transcriptional axes described by D’Costa et al. but did not distinguish patients by immunotherapy response. No genes were significantly differentially expressed after multiple testing correction; however, CD34 showed the strongest nominal association with responder tumors and was upregulated in this group, but did not retain statistical significance after adjustment. CD34 expression also correlated with CD8+ T-cell infiltration. Our findings confirm the applicability of the D’Costa molecular signature and identify CD34 as the strongest nominally associated transcript in responder tumors, warranting further orthogonal and prospective validation.

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.

PURPOSE:Adolescents and young adults (AYA; 15-39 years) represent a distinct oncology population with specific biological and psychosocial needs. Despite growing awareness, AYA patients often face fragmented care between pediatric and adult settings, resulting in diagnostic delays, limited clinical trial access, and inadequate psychosocial support. In 2021, the AIOM-AIEOP AYA Working Group was established in Italy to promote awareness and address these challenges. METHODS:An anonymous, voluntary online survey was designed by the AIOM-AIEOP AYA Working Group and distributed during the AIOM National Congress (November 2024). Using iPads at a dedicated booth, oncologists and other healthcare professionals completed a questionnaire exploring knowledge, perceptions, and access to AYA-focused services. Data were analyzed using descriptive statistics. RESULTS:Ninety-seven professionals participated (median age 34 years; 75% female; 56% medical oncologists). Although 86% reported access to genetic counseling and 84% to fertility preservation services, only 18% had AYA-dedicated spaces and 21% employed trained AYA-specific staff. Forty-four percent felt competent in assessing hereditary cancer syndromes, and fewer than 25% were aware of AYA-focused research or trials. Psychological support was commonly available, whereas educational coaching and peer support groups were rare (5% each). Lifestyle counseling was frequent, but structured survivorship care and long-term follow-up were limited. CONCLUSIONS:This survey reveals substantial gaps in AYA oncology services in Italy, particularly regarding dedicated staff, infrastructure, and training. National coordination and implementation of standardized frameworks, such as through the AIOM-AIEOP network, are essential to ensure equitable, comprehensive care for AYA patients.

PURPOSE:Comprehensive genomic profiling (CGP) is increasingly adopted in the management of patients affected by GI cancers. However, the applicability, performance, and clinical utility of CGP in the real-world setting are still undefined. METHODS:We retrospectively evaluated CGP performance and clinical benefit in consecutive patients with GI tumor at the Veneto Institute of Oncology-IRCCS, Padua. We assessed CGP success and its advantage over routine diagnostics in detecting actionable molecular targets. A custom list of gain alterations was defined, including targets not classified as ESMO Scale for Clinical Actionability of molecular Targets tier IA at the time of analysis. RESULTS:Of the 1,450 samples, 140 (9.7%) were inadequate for CGP. Failure was mainly due to low quantity of extracted tumor DNA (P = .002). Of the 1,265 metastatic patients, GAs were detected in 355 (28.1%) cases, of whom 55 (15.5%) were treated with targeted therapy. Survival did not differ between patients with no GAs and those with GAs who were not treated accordingly (median overall survival 12.0 v 10.9 months), whereas it was significantly longer for those receiving treatment for actionable GAs (26.4 months). This advantage was confirmed in an exploratory, inverse probability of treatment-weighted analysis (adjusted hazard ratio, 0.72 [95% CI, 0.58 to 0.89]; P = .002). Among 283 (83.7%) untreated patients with complete follow-up, 41.6% did not receive targeted therapy due to lack of clinical trial or failure to meet inclusion criteria. CONCLUSION:Appropriate specimen selection and early molecular assessment at the time of advanced disease diagnosis are essential to detect clinically actionable molecular alterations and therapeutic opportunities in patients with GI cancers. Our results support CGP in comprehensive cancer centers.

177 Background: Poly(ADP-ribose) polymerase inhibitors (PARPi) + ARPI + ADT have improved clinical outcomes versus ARPI + ADT alone in pts with metastatic castration-resistant prostate cancer (mCRPC), particularly those with BRCA mutations. Interim efficacy results from the Phase 1/2 PETRANHA study (NCT05367440) showed high rates of undetectable prostate specific antigen (uPSA) levels in pts with mHSPC who received saruparib, a PARP1 selective inhibitor, + ARPI + ADT, irrespective of homologous recombination repair mutation (HRRm) status (Azad A, et al. ESMO 2025 [2384MO]). We report updated efficacy and safety results for pts with mHSPC. Methods: Pts received oral saruparib 60 mg once daily + physician’s choice of ARPI (enzalutamide, abiraterone acetate or darolutamide) + ADT. ADT for up to 6 months prior to consent was permitted. Prior chemotherapy for metastatic prostate cancer was not allowed. Treatment continued until disease progression or intolerable toxicity. Results: At data cutoff (June 10, 2025), 93 pts with mHSPC were treated with saruparib + ARPI (enzalutamide [n=3], abiraterone acetate [n=14] or darolutamide [n=76]) + ADT, with a median follow-up of 16.4 months (min–max, 0.0–34.8). Overall, 55.9% (52/93) of pts had high volume disease, 12.9% (12/93) had visceral metastasis, and the baseline median PSA level was 2.5 ng/mL. In response evaluable pts (34/93), the objective response rate (ORR) was 82.4% (28/34; 80% CI, 71.1–90.5), including 5 complete responses (14.7%). The confirmed uPSA rate at any time was 69.9% (65/93; 80% CI, 63.0–76.1) and confirmed 52-week uPSA rate was 76.7% (46/60; 80% CI, 68.2–83.7). For pts with HRRm versus non-HRRm, ORR was 100% (4/4) and 85.7% (12/14); confirmed uPSA rate at any time was 71.4% (10/14) and 70.6% (24/34); and confirmed 52-week uPSA rate was 77.8% (7/9) and 73.9% (17/23), respectively. The combination had a manageable safety profile (Table). Conclusions: In pts with mHSPC, saruparib + ARPI + ADT induced high ORRs and high 52-week uPSA rates. Efficacy was observed regardless of HRRm status. The safety profile of the combination was manageable with no new safety signals. These findings warrant confirmation in the ongoing Phase 3 EvoPAR-Prostate01 trial. Clinical trial information: NCT05367440 . Safety summary (N=93). Median total duration of saruparib / ARPI exposure, months (min–max) 16.3 (0.7–35.6) / 16.5 (0.7–35.6) Safety parameter, n (%) Any AECausally related to saruparib 92 (98.9)83 (89.2) Any Grade ≥3 AECausally related to saruparib 45 (48.4)29 (31.2) Any serious AECausally related to saruparib 24 (25.8)8 (8.6) Saruparib / ARPI discontinuation due to AE* 7 (7.5) / 3 (3.2) Saruparib / ARPI dose reduction due to AE* 24 (25.8) / 3 (3.2) Saruparib / ARPI interruption due to AE* 52 (55.9) / 36 (38.7) *Irrespective of the action taken on other drugs. AE, adverse event.

Choriocarcinoma is a malignant neoplasia which develops from trophoblastic cells. In males it is rare and often associated with other non-seminomatous germ cell tumours of the testis. Choriocarcinoma often presents with metastatic disease and elevated βHCG levels. Usually, patients' symptoms are associated with the different metastatic sites and they can be severe or even life-threatening. Moreover, choriocarcinoma is chemosensitive and the administration of chemotherapy with curative intent may lead to tumour-lysis syndrome and the more specific choriocarcinoma syndrome (CS). Therefore, the treatment of metastatic choriocarcinoma is complex, involving both oncological therapy and the management of acute complications. This review explores choriocarcinoma in males, focusing on its clinical presentation, pathogenetic mechanisms, and treatment options, including investigational therapies. Additionally, we aim to highlight the severe complications of CS and discuss its management strategies.

BACKGROUND: Neoadjuvant cisplatin-based chemotherapy is a standard therapy for muscle-invasive bladder cancer. The efficacy and safety of neoadjuvant and adjuvant (perioperative) enfortumab vedotin-pembrolizumab as compared with neoadjuvant cisplatin-based chemotherapy in persons with this cancer are unclear. METHODS: We conducted a phase 3, open-label, randomized trial involving adults with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy and radical cystectomy with pelvic lymph-node dissection (cystectomy). Participants were assigned to receive neoadjuvant enfortumab vedotin-pembrolizumab (4 cycles; enfortumab vedotin [1.25 mg per kilogram of body weight on days 1 and 8] and pembrolizumab [200 mg on day 1] every 3 weeks), cystectomy, and 5 cycles of enfortumab vedotin and 13 cycles of pembrolizumab as adjuvant therapy or to receive neoadjuvant cisplatin-gemcitabine (4 cycles; cisplatin [70 mg per square meter of body-surface area on day 1] plus gemcitabine [1000 mg per square meter on days 1 and 8] every 3 weeks) and cystectomy. The primary end point was event-free survival; key secondary end points were overall survival and pathological complete response. Safety was assessed. RESULTS: A total of 405 participants were assigned to receive enfortumab vedotin-pembrolizumab and 403 to receive cisplatin-gemcitabine. The median time from randomization to the data-cutoff date was 33.6 months (range, 22.5 to 53.6). A total of 86.7% of the participants in the enfortumab vedotin-pembrolizumab group and 89.6% of those in the cisplatin-gemcitabine group underwent cystectomy. At 2 years, estimated event-free survival was 79.4% with enfortumab vedotin-pembrolizumab and 66.2% with cisplatin-gemcitabine (hazard ratio for an event or death, 0.53; 95% confidence interval [CI], 0.41 to 0.70; P<0.001); estimated overall survival was 86.9% and 81.3%, respectively (hazard ratio for death, 0.65; 95% CI, 0.48 to 0.89; two-sided P = 0.006). A pathological complete response occurred in 55.8% and 32.5% of the participants (P<0.001). The incidence of grade 3 or higher adverse events of any cause was 75.7% with enfortumab vedotin-pembrolizumab and 67.2% with cisplatin-gemcitabine. CONCLUSIONS: Among participants with muscle-invasive bladder cancer eligible for cisplatin-based chemotherapy, perioperative enfortumab vedotin-pembrolizumab led to significantly better event-free and overall survival outcomes and a significantly higher incidence of pathological complete response than neoadjuvant cisplatin-gemcitabine, but with more adverse events of grade 3 or higher. (Funded by Merck Sharp and Dohme and others; KEYNOTE-B15/EV-304 ClinicalTrials.gov number, NCT04700124.).

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 .

Metastatic renal cell carcinoma remains clinically challenging because of heterogeneous outcomes and limited predictive biomarkers for immunotherapy. We performed an explainable machine learning analysis using data from the multicenter retrospective Meet-URO 15 study, including 571 patients with metastatic renal cell carcinoma treated with second-line or later nivolumab. Clinical and inflammatory variables were used to develop classification models for disease control rate, progression-free survival at 3 and 9 months, and overall survival at 6, 18 and 24 months, as well as survival models for continuous progression-free and overall survival. Model performance was assessed using weighted F1-score for classification and concordance index for survival analysis, with interpretability provided through Shapley additive explanations. The best classification performance was observed for 6-month overall survival using a support vector machine model combined with minimum redundancy maximum relevance feature selection, achieving an F1-score of 0.81 on the test set and 0.77 in external validation. In survival analysis, random survival forest achieved a test-set concordance index of 0.68 for overall survival. Inflammatory indices, IMDC score, hemoglobin, lymphocytes and platelets consistently emerged as relevant prognostic features. These findings support explainable machine learning as a transparent approach to refine outcome prediction in immunotherapy-treated metastatic renal cell carcinoma.

4568 Background: Ave 1L maintenance is a recommended treatment option for patients (pts) with aUC without progression after 1L platinum-based chemotherapy (PBC). In the JAVELIN Bladder Medley phase 2 trial (NCT05327530), 1L maintenance with Ave + SG (Trop-2–directed antibody-drug conjugate) improved progression-free survival (PFS) vs Ave mono (primary endpoint). In pts with aUC, presence of visceral metastases (including liver or lung) is associated with poorer prognosis. We report updated subgroup analyses from the primary analysis of JAVELIN Bladder Medley based on metastatic site. Methods: Pts with unresectable locally advanced or metastatic UC without progression after 4-6 cycles of 1L PBC were randomized 2:1 to receive Ave + SG or Ave mono, stratified by presence of visceral metastases at start of 1L PBC. Primary endpoints were investigator-assessed PFS (measured from randomization) and safety; overall survival (OS) was a secondary endpoint. For visceral and nonvisceral subgroups, PFS and OS data in the Ave mono arm were extended per protocol using propensity score–weighted data from the JAVELIN Bladder 100 phase 3 trial; extended data were not available for other subgroups. Results: At the start of 1L PBC, of 74 and 37 pts in the Ave + SG and Ave mono arms, respectively, 37 (50.0%) and 19 (51.4%) had visceral metastases, 20 (27.0%) and 11 (29.7%) had lung metastases, 17 (23.0%) and 7 (18.9%) had liver metastases, 17 (23.0%) and 11 (29.7%) had bone metastases, and 26 (35.1%) and 11 (29.7%) had lymph node–only disease. At data cutoff (Apr 28, 2025), in the Ave + SG and Ave mono arms, respectively, median follow-up for PFS was 15.7 and 25.1 mo. Across all subgroups, PFS was prolonged with Ave + SG vs Ave mono (Table); OS analyses were immature. In the Ave + SG and Ave mono arms, respectively, grade ≥3 treatment-related adverse events occurred in 72.2% and 5.6% of pts with visceral metastases, 57.9% and 0% of pts with lung metastases, 82.4% and 0% of pts with liver metastases, 82.4% and 0% of pts with bone metastases, 70.3% and 5.6% of pts with nonvisceral metastases, and 76.9% and 9.1% of pts with lymph node–only metastases. Conclusions: In the primary analysis of JAVELIN Bladder Medley, Ave + SG as 1L maintenance improved PFS vs Ave mono, irrespective of metastatic site. Clinical trial information: NCT05327530 . PFS, median (95% CI), mo Ave + SG Ave mono HR (95% CI) Site of metastases at start of 1L PBC Visceral* 9.03 (5.62-13.80) 2.20 (1.91-3.71) 0.49 (0.28-0.84) Nonvisceral 14.69 (7.43-NE) 7.33 (4.21-11.10) 0.61 (0.33-1.13) Lung 8.77 (4.17-9.46) 1.81 (0.07-9.26) 0.43 (0.17-1.09) Liver 8.77 (5.55-9.36) 2.69 (1.91-NE) 0.48 (0.17-1.32) Bone 9.26 (5.49-17.64) 2.33 (0.07-5.45) 0.40 (0.16-0.99) Lymph node only 14.00 (7.43-NE) 7.59 (1.87-NE) 0.65 (0.26-1.66) *Pts could have ≥1 site of visceral metastases.HR, hazard ratio; NE, not estimable.

In advanced urothelial carcinoma (UC), the prognostic impact of metastatic site and burden during avelumab maintenance therapy remains poorly defined. We performed a sub-analysis of the Italian multicenter retrospective–prospective observational study Meet-URO 25, including patients with advanced UC who received avelumab maintenance after disease control with first-line platinum-based chemotherapy. We assessed the association between metastatic site and number of metastatic sites at the start of avelumab and clinical outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). A total of 243 patients were included. Lymph nodes (79.0

Background: Germline and somatic variants in DNA Damage Repair (DDR) genes are found in approximately one-fourth of patients with metastatic prostate cancer (PC). However, their precise prognostic role and predictive impact on standard therapies remain controversial. Methods: This retrospective, single-center study evaluated the prevalence of germline/somatic DDR aberrations in 287 eligible patients with metastatic prostate cancer (mPC), treated between 2017 and 2022. Clinical characteristics and treatment outcomes (PFS and OS) for chemotherapy (taxanes) or next-generation hormonal therapies (NHT) were compared between DDR-mutated (DDRmut) and wild-type (DDRwt) cohorts. Results: Sixty-three patients (21.9%) were DDRmut, with BRCA2 (12.5%), ATM (3.1%), and BRCA1 (1.39%) being the most common alterations. A family history of breast, ovarian, or prostate cancer strongly predicted DDRmut status (47.0% vs. 14.0%, p = 0.0001). Tissue samples remained evaluable for sequencing up to 180 months from collection. Overall baseline characteristics were similar between cohorts, and BRCA1/2- and ATM-mutated patients treated with first-line taxanes for mCRPC presented with non significantly highermedian OS compared to DDRwt patients (70 vs. 36 months; p = 0.30). On the contrary, the DDRmut subgroup showed a trend toward shorter PFS (12 vs. 18 months; p = 0.04) when treated with first-line NHT. No significant differences were observed with third-line Cabazitaxel. Conclusions: Formalin-fixed paraffin-embedded (FFPE) prostate tissue is highly reliable for DDR, possibly integrating novel liquid biopsy approaches for DDR evaluation. In a real-world setting, BRCA1/2 and ATM variants identify a distinct molecular subgroup that derives preferential survival benefit from first-line taxanes over standard hormonal intensification.

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: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.

The increasing incidence of bone metastases frequently leads to skeletal-related events (SREs) and pain. While multidisciplinary management is recommended by scientific societies, a standardized model remains undefined. An example can be provided by the Osteoncology multidisciplinary outpatient clinic (OMC) of the Veneto Oncology Institute, created to offer support to patients with bone metastases. Patients with bone metastases are evaluated by a multidisciplinary team since 2013. Access to the OMC is regulated by an internal protocol and a form filled out by the referring physicians, which establishes the priority of access and the specific query for the multidisciplinary team. We analyzed the characteristics and outcome of OMC visits of all patients who accessed between January 2018 and June 2023. All data were retrieved from a prospectively managed database. 2,200 patients were evaluated at OMC, with a median age of 66 years. Breast (33.3

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:Issues related to end-of-life decisions (ELDs) generate impassioned debates in society. Our study aimed at investigating attitudes in care of cancer patients at the end-of-life (EOL); ascertaining the opinion of healthcare professionals (HCPs), patients, and caregivers. METHODS:An anonymous and self-administered questionnaire was delivered to HCPs (physicians, nurses, psychologists, and social workers), patients and family caregivers at Veneto Institute of Oncology, Italy, and 425 questionnaires were collected (136 HCPs, 171 patients, 118 caregivers). RESULTS:Withholding life-sustaining treatment (LST) was declared by 11.3% of physicians and nurses and withdrawing by 19.4%, whereas 46.8% declared starting LST, and 48.4% did not discontinue LST. Most HCPs (75.7%) were in favor of patient's right to anticipate EOL, and 86.4% of withholding/withdrawing LST upon patient's request, with 62.4% HCPs agreeing on lethal drug doses to be allowed upon request of the patient. The majority (80.1%) disagreed that "life is an unavailable asset and there is no right to die". For patients and caregivers, in ELDs greater value was given to self-determination first, with family members and trustees' subsequent involvement. A considerable number of HCPs reported feeling inadequate to communicate bad news. CONCLUSION:Despite the limitations imposed by the cross-sectional nature, this study adds information with regard to EOL in oncology setting in Italy. Our study shows that an attitude to prolonging patient's life in ELDs is still prevalent among HCPs in an Italian oncological setting, although there are signs of change. Communicating bad news emerges as an issue, along with HCPs' awareness that they need more education and training.