OBJECTIVE:To bear the evidence that laparoscopy is the possible new treatment of choice in the management of retroperitoneal disease in patients with testicular cancer. The surgical management of retroperitoneal lymph nodes is a crucial step in the multidisciplinary treatment of testicular germ cell tumors. Laparoscopic retroperitoneal approach poses technical challenges in urologic oncology. This study reports on the safety, efficacy, and short-term oncological outcomes of laparoscopic retroperitoneal lymph node dissection at a tertiary referral hospital. METHOD:Prospective, observational, descriptive study conducted from 2021 to 2023, including 83 patients who underwent laparoscopic retroperitoneal lymph node dissection. RESULTS:Eleven cases of primary laparoscopic retroperitoneal lymph node dissection (13.3%), 36 standard (43.3%), 22 salvage (26.5%), 11 desperation (13.3%), and 3 redo cases (3.6%) were performed. In primary cases, 81.9% of patients had positive nodes (pN1-3). The conversion rate to open surgery was 6%. Bleeding, lymph node volume, pre-lymphadenectomy markers, chemotherapy, initial histology, and lymph node histology were not risk factors for conversion = Mean surgical time was 250 minutes. There were no major complications (organ injury, vascular injury) or need for blood transfusion = Mean blood loss was 60 mL. Recurrence rate was 9.6%, with recurrence-free survival of 36.7 months. CONCLUSIONS:The reported experience demonstrated the safety and efficacy of primary laparoscopic retroperitoneal lymph node dissection, as well as post-chemotherapy cases. Laparoscopic approach allows for early patient recovery without compromising oncological outcomes. It is advisable to perform this surgery in high-volume centers with experienced surgeons in retroperitoneal surgery.

Testicular germ cell tumors (TGCTs) are the most common solid malignancies in young men and, despite high cure rates with cisplatin-based multimodal therapy, a clinically relevant subset of patients develops relapsed, platinum-refractory, or treatment-resistant disease with limited salvage options and substantial long-term morbidity. This unmet need has renewed interest in immunotherapy, yet the experience in TGCT has been notably less successful than in other malignancies. Although TGCTs often display PD-L1 expression, tumor-infiltrating lymphocytes, and other features suggestive of immune engagement, immune checkpoint inhibitors have produced largely disappointing results in unselected patients, underscoring the complexity of immune regulation in this immune-privileged disease. Recent conceptual advances place microRNAs (miRNAs) at the center of this problem. Beyond their established diagnostic and prognostic value, miRNAs are increasingly recognized as upstream regulators of immune checkpoints, antigen-presentation pathways, cytokine signaling, macrophage polarization, dendritic-cell and T-cell function, and extracellular-vesicle-mediated tumor–immune crosstalk. This positions miRNAs not only as biomarkers of disease activity, but also as plausible determinants of immunotherapy sensitivity or resistance. At the same time, the field remains marked by important controversies: PD-L1 expression alone is an unreliable predictor of response; the relative contribution of low tumor mutational burden, testicular immune privilege, and microenvironmental suppression remains unresolved; and many proposed TGCT-associated miRNAs with an immunoregulatory role are still inferential rather than causally validated in disease-specific models. Accordingly, major gaps persist in defining which miRNAs are true functional drivers of immune escape in seminomatous versus non-seminomatous TGCT, how they interact with therapy-induced tumor evolution, and which delivery platforms can achieve safe, tumor-directed modulation. We argue that the next phase of the field should move beyond descriptive biomarker studies toward mechanism-based, TGCT-specific translational strategies integrating miRNA mimics, antagomirs, extracellular vesicles, or miRNA-augmented cellular therapies with immune-priming approaches such as epigenetic therapy, radiotherapy, vaccines, or CAR-T platforms. Such a framework could enable more precise biological stratification and improve the efficacy, durability, and tolerability of immunotherapy in refractory TGCT.

Objetivo: Apoyar la evidencia de que la laparoscopia es el posible nuevo tratamiento de elección en el control de la enfermedad retroperitoneal en pacientes con cáncer de testículo. El manejo quirúrgico de los ganglios retroperitoneales es un paso fundamental en el tratamiento multidisciplinario de los tumores testiculares de células germinales. El abordaje laparoscópico del retroperitoneo es un desafío técnico en la urología oncológica. En el siguiente trabajo reportamos la seguridad, la eficacia y los resultados oncológicos a corto plazo de la linfadenectomía retroperitoneal laparoscópica en un instituto de referencia de tercer nivel. Método: Estudio prospectivo, observacional, descriptivo, de enero de 2021 a septiembre de 2023, que incluyó 83 pacientes sometidos a linfadenectomía retroperitoneal laparoscópica. Resultados: Se realizaron 11 procedimientos de linfadenectomía retroperitoneal laparoscópica primaria (13.3%), 36 (43.3%) estándar, 22 (26.5%) de salvamento, 11 (13.3%) de desesperación y 3 (3.6%) redo. En los casos de linfadenectomía primaria, el 81.9% de los pacientes tuvieron ganglios positivos (pN1-3). La tasa de conversión a cirugía abierta fue del 6%. El sangrado, el volumen ganglionar, los marcadores prelinfadenectomía, la quimioterapia, la histología inicial y la histología de los ganglios no fueron factores de riesgo para conversión = El tiempo quirúrgico medio fue de 250 minutos. No hubo complicaciones mayores (lesiones a órganos o lesiones vasculares) ni necesidad de transfusión hemática. El sangrado medio fue de 60 ml. El 9.6% de los pacientes tuvieron recurrencia; la sobrevida libre de recurrencia fue de 36.7 meses. Conclusiones: La experiencia reportada demuestra la seguridad y la eficacia de la linfadenectomía retroperitoneal laparoscópica primaria, así como en tumores residuales tras quimioterapia. El abordaje laparoscópico permite una pronta recuperación de los pacientes sin afectar los resultados oncológicos. Es recomendable realizar este tipo de cirugía en centros de alto volumen y en manos de cirujanos experimentados en cirugía retroperitoneal.

BACKGROUND AND OBJECTIVE:Genomic characterization of metastatic prostate cancer (mPCa) plays a pivotal role in guiding precision oncology. This study aimed to evaluate the feasibility of combining radiomics and clinical data within a machine learning (ML) framework to non-invasively predict key genomic mutations in patients with mPCa undergoing PSMA PET imaging. METHODS:A retrospective cohort of 14 mPCa patients who underwent [18 F]PSMA-1007 PET/CT was analysed. Prostate and metastatic lesions were segmented, and radiomics features were extracted. Somatic genomic alterations were obtained from formalin-fixed paraffin-embedded tissue samples using FoundationOne CDx testing. Six ML algorithms - Discriminant Analysis, Support Vector Machines, K-Nearest Neighbours, Neural Networks, Random Forest, and Boosting - were trained using a 5-times repeated pipeline with 80/20 train/test split, LASSO feature selection, and 5-fold cross-validation. Model performance was assessed using accuracy, AUC, sensitivity, specificity, precision, and F-score. KEY FINDINGS:Fourteen patients with mPCa were included, and 46 lesions were analysed. Genomic alterations included mutations in TP53, TMPRSS2, PTEN, BRCA1/2, ATM, and others. Owing to data limitations, mutations other than TP53, TMPRSS2, and PTEN were grouped into a composite "OTHER" category. The best-performing clinical-radiomics ML models achieved AUCs of 91.11% (TP53), 84.44% (TMPRSS2), 80.00% (PTEN), and 77.78% (OTHER). Selected feature stability was consistent across repeated runs. CONCLUSIONS AND CLINICAL IMPLICATIONS:Clinical-radiomics ML models based on PSMA PET imaging show promising accuracy in predicting actionable genomic alterations in mPCa. These findings support further investigation into radiogenomics modelling as a complementary, non-invasive tool to inform molecular profiling and treatment stratification.

e17116 Background: Molecular characterization of prostate cancer (PCa) has allowed development in targeted therapies design; with molecular imaging as PSMA-PET, they both determine precision oncology and personalized medicine. Currently, genomic advancements have lead to mayor prognostic and predictive implications in oncologic outcomes, aim in this study was to evaluate and describe PSMA-PET quantitative parameter patterns in de novo metastatic hormonosensitive prostate cancer (mHSPC) and the associations with somatic pathogenic variants. Methods: We conducted a retrospective analysis of 45 patients referred to the nuclear medicine’s department in Mexico’s National Cancer Institute for a staging PSMA-PET/CT, with confirmed PCa histopathological results and with new generation sequency (NGS) testing of the primary tumour. Results: 28.89% (n=13) of patients had confirmed pathogenic (or likely pathogenic) variant (PV) mutations in HRR or TS genes; 35.56% (n=16) had variants of unknown significance (VUS) mutations, and 35.56% (n=16) of patients had a negative NGS test. PV and VUS detected are described in table 1, Coexisting PV (≥2) were found in 23% and 37.5% in VUS group. Differences between group 1 and 3 were statistically significant (Mann Whitney’s U p=0.0056). In the mutational status analysis, group 1 and group 2 did not have any significant difference in overall survival ( p=0.731 ); opposed to statistical results from group1 and 2 (altogether) compared to group 3 ( p=0.055 ). We defined TTV cutoff value at 94 ml, for worse overall survival by ROC curves, and was used to stratify patients according to TTV (>94 ml vs <94 ml) and mutational status (VP carriers + VUS carriers vs non-mutated); where VP and VUS carriers with >94 ml TTV exhibited a worse molecular and clinical prognostic behavior, resulting in a markedly decreased overall survival (p =0.0218 ) Log-rank Mantel Cox’s. Conclusions: Mutations in the HRR gene are associated with increased metabolic substrate requirements for DNA base pairs as a compensatory mechanism for the effects of such mutations. Folate hydrolase and glutamate carboxypeptidase are core functions of PSMA and play a role as a molecular marker in cellular adaptive mechanisms to genomic alterations. Our findings suggest that the integration of molecular imaging and genomic profiling has an impact on overall survival. Mutational and PSMA SUVmax characteristics. Group PV carriers (Group 1) VUS carriers (Group 2) Non-mutated (Group 3) SUVmax (Median) SUVmax (Range) 16.5 (8.2-39.9) 9.3 (3.1-28.86) 9.75(4.1-16.6) Genes p53(n=4) 30.8% ATM 18.75%(n=3) CHECK2(n=2) 15.4% p53 12.5%(n=2), ATM(n=2) 15.4% RAD54D 6.25% (n=1) FANCA(n=1) 7.7% CHECK2 6.25% (n=1) RADB51(n=1) 7.7% CDK12 6.25% (n=1) FANCL 6.25% (n=1) BRCA1 6.25% (n=1)

BACKGROUND & AIMS:Phase angle (PA), derived from bioelectrical impedance analysis (BIA), is a non-invasive marker of cellular integrity and nutritional status. While its prognostic value has been demonstrated in various malignancies, evidence in metastatic prostate cancer (mPCa) is scarce. This study aimed to evaluate the association between PA and overall survival (OS) in patients with mPCa receiving androgen deprivation therapy (ADT). METHODS:We conducted a retrospective cohort study including 103 patients with confirmed mPCa undergoing ADT. PA was measured using multi-frequency BIA and patients were categorized into two groups: PA ≤ 4.0° and PA > 4.0°. Clinical, anthropometric, and body composition data were collected. OS was estimated using Kaplan-Meier analysis, and Cox proportional hazards models were used to assess the association between PA and mortality. RESULTS:Patients with PA ≤ 4.0° (n = 24; 23.3 %) had significantly lower fat-free mass and higher fat mass percentage compared to those with PA > 4.0° (n = 79; 76.7 %). A significantly higher proportion of patients with PA ≤ 4.0° experienced disease progression (79.2 % vs. 45.6 %, p = 0.004). Kaplan-Meier analysis showed reduced survival in the low PA group (Log-rank p = 0.0043). In multivariate Cox regression, PA ≤ 4.0° was independently associated with higher mortality risk (HR: 4.603; 95 % CI: 1.653-12.817; p = 0.003). CONCLUSIONS:Low phase angle is independently associated with reduced survival in men with mPCa undergoing ADT. PA may serve as a reliable, low-cost biomarker for risk stratification and nutritional assessment in this population.

34 Background: Prostate cancer represents a strong economic and social burden in the world. Imaging, pathology report and prostate specific antigen are the cornerstone for decision making. PSMA imaging with PET/CT has demonstrated superiority over conventional imaging, however, its availability is limited in countries with emerging economies. 99mTc-based imaging is widely used and has been favored by the development of new inhibitors targeting PSMA. Methods: We analyzed retrospectively 119 men with a histopathological diagnosis of prostate cancer obtained through transrectal biopsy or with clinical suspicion due to elevated PSA levels and physical examination findings. 68 were classified as high-risk and 51 as very high-risk, and referred for staging with [99mTc]Tc-iPSMA SPECT/CT between July 2022 and July 2024. The waiting times for initiating treatment were compared with a strategy based on PET/PSMA. Also number of lesions in patients with dual imaging with [99mTc]Tc-MDP and [99mTc]Tc-iPSMA was analyzed and assessed the changes in intention to treat. Results: Mean age of patients was 69.2 y/o (range 55-89 y/o), mean PSA level of staging group was 78.5 ng/mL (range 28.5-1667 ng/mL). Waiting time for a [99mTc]Tc-iPSMA was 7.2 days (+/- 1.5 days) versus 67.5 days (+/- 11.8 days) for [18F]F-iPSMA PSMA-1007. An additional study was required in 15.1% (n=18) of patients (n=13 PET/CT [18F]F PSMA-1007, 5 abdominal magnetic resonance). 36 patients had dual studies, observing 108 lesions with [99mTc]Tc-iPSMA and 114 with [99mTc]Tc-MDP, 6 with PSMA and 12 with MDP did not show anatomical changes. These findings did not modify the clinical stage or treatment intention. Overall, 590 lesions were identified in 119 patients, 101 in prostate, 267 in bone (diffuse disease in bone was considered as a single lesion), 135 in regional lymph nodes, and 87 in non-regional lymph nodes. Size range of lymph nodes detected were 0.5 mm to 25 mm. The change in management occurred in 23% patients (n=28); the changes were from ADT alone to doublet (ADT and Docetaxel) (n=11), from Radiotherapy to the pelvis to ADT + Docetaxel (n=8), from Radiotherapy to the pelvis to triplet (ADT+ Docetaxel + ARPi) (n=5), from ADT + RT to surgery (n=2), from ADT alone to ADT + SBRT (n=2). Conclusions: [99mTc]Tc-iPSMA SPECT/CT is an efficient alternative tool to [18F]F-iPSMA PSMA-1007, the results provide sufficient information to allow a significant change in intention to treat, significantly reducing waiting times, especially in countries where equipment availability PET is limited. These results support the development of public policies that promote the use of this type of radiopharmaceuticals to expand access to the new generation imaging modality and provide a benefit in the clinical management of prostate cancer especially in countries with low PET/CT infrastructure.

Metastatic clear-cell renal cell carcinoma (mccRCC) remains a major cause of morbidity and mortality among patients with kidney cancer. Over the past two decades, mccRCC treatment has significantly evolved with the incorporation of antiangiogenic tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs) as the cornerstone of systemic therapy. In response, major international guidelines have continuously updated their recommendations according to emerging evidence from clinical trials. We provide an overview of current management recommendations for mccRCC, including cytoreductive nephrectomy (CN), active surveillance (AS), first-line treatment, and subsequent-line treatment. While upfront CN is no longer recommended for unselected patients, it remains an option for carefully selected patients with a limited metastatic burden. AS can be considered for those with slow-growing, asymptomatic, low-volume disease. First-line treatment strategies now prioritize ICI based combinations tailored to patient risk factors, comorbidities, and disease characteristics. In subsequent lines, treatment sequencing remains a challenge, with ongoing research needed to refine therapeutic choices. As new evidence emerges, treatment strategies must continue to adapt, underscoring the need for ongoing updates to clinical guidelines. PATIENT SUMMARY: Clinical trials are continuously identifying new treatments for advanced kidney cancer. Our guideline provides updated treatment recommendations from international societies that are based on evidence from these trials. Personalized treatment can improve the care and outcomes for patients with advanced kidney cancer.

Renal cell carcinoma (RCC) stands for 2-3 % of all neoplasms worldwide. The most important risk factors identified for RCC are obesity, hypertension, type 2 diabetes mellitus, and tobacco use. Nowadays, more than 50 % of RCCs are detected incidentally. There are multiple therapeutic strategies to treat RCC, ranging from active surveillance or nephrectomy for localized disease to combinations of targeted therapies and immunotherapy for patients with advanced disease.