Introduction: Four approved immune-based combinations for untreated metastatic renal carcinoma have demonstrated survival benefits. The ARON-1 study (NCT05287464) analyzed real-world data of patients with metastatic renal cell carcinoma receiving first-line immuno-oncology combinations. This sub-analysis is focused on the nivolumab plus cabozantinib effectiveness.Methods: We conducted a retrospective study across 52 centers in 17 countries, including patients with metastatic renal carcinoma treated with first-line nivolumab plus cabozantinib, regardless of histologic characteristics, performance status, or risk by IMDC prognostic model. Patients with incomplete medical data were excluded. The primary objective of this sub-analysis of the ARON-1 study was to evaluate the real-world effectiveness and safety.Results: A total of 333 patients were treated with nivolumab plus cabozantinib, clinical characteristics included ECOG performance status ≥2 20%, non-clear cell histology 16%, sarcomatoid de-differentiation 12%, and poor-risk by IMDC 28%. At a median follow-up of 15.9 months (95%CI 11.2-44.0), the median overall survival was not reached (40.0–NR), the probability of survival at 2 years was 75%, while median progression free survival was 33.7 months (95%CI 21.1-38.9). In the entire cohort, an objective response was observed in 58%, with 6% complete responses, and a median duration of response of 38.9 months (95%CI 33.7–NR). At multivariate analysis, adverse prognostic factors for overall survival included ECOG performance status ≥2, sarcomatoid de-differentiation, brain and bone metastases, and poor IMDC group. In the safety analysis, the incidence of grade 3 or higher toxicity was 37%, with hypertension and hand-foot syndrome being the most frequent adverse events.Conclusion: The findings in the present real-world study reaffirm the clinical benefits and safety of the nivolumab plus cabozantinib combination across all subgroups, including populations that are generally excluded from clinical trials for whom data is often missing. Poor performance status, sarcomatoid de-differentiation, bone or central nervous system metastases and IMDC poor risk group were confirmed as negative prognostic factors.

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: 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.

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/Objective: Prostate cancer (PCa) represents the second-most common cancer among men worldwide. Obesity is generally considered as a risk factor for cancer and it has been associated with a 20–30% increased risk of PCa death. The present systematic review and meta-analyses aimed to highlight any existing trends between prostate neoplasm stages according to normal weight, overweight and obesity conditions. Methods: All interventional records such as randomized clinical trials, quasi-experimental studies and observational studies were included in the present systematic review and meta-analysis which reported PCa stages according to Gleason (GS) or TNM scores according to the BMI-related incidence, as normal weight, overweight and obesity groups. Results: Twenty-nine studies were included in the present study. As regards the GS scoring system, 1.09% of high grade in GS was reported among PCa normal weights. Among PCa overweights, 0.98% of low grade was registered in GS. The same trend was recorded among obese PCa patients, since 0.79% of low grade in GS was also registered. As regards TNM scores, both normal weight, overweight and obese PCa patients registered a significant incidence in non-advanced TNM score, without any significant differences considering higher TNM assessments. Conclusions: Although the literature seemed to be more in favor of associations between BMI and GS, no specific mechanisms were highlighted between obesity and PCa progression. In this regard, the low androgen microenvironment in obese men could play an important role, but further studies will be necessary in this direction.

Immune checkpoint inhibitor-related pneumonitis (CIP) is an uncommon but clinically relevant toxicity in renal cell carcinoma (RCC), where immune checkpoint inhibitors are frequently used either as dual immunotherapy or in combination with VEGF-targeted tyrosine kinase inhibitors. In RCC, CIP poses specific diagnostic challenges because respiratory symptoms and computed tomography findings may overlap with pulmonary metastases, infections, thromboembolic events, heart failure, and TKI-related lung toxicity. This review summarizes the incidence of CIP across pivotal RCC trials and real-world cohorts, compares its epidemiology with non-small cell lung cancer, and discusses clinical presentation, radiological patterns, differential diagnosis, and current management strategies. Particular attention is given to RCC-specific mechanisms, including immune-mediated alveolar injury, T cell activation, cytokine dysregulation, macrophage activation, GSDME-mediated pyroptosis, and the potential contribution of VEGF pathway inhibition to pulmonary inflammation. We also review risk factors, steroid-refractory disease, second-line immunosuppression, and the unresolved issue of ICI rechallenge after pneumonitis. A better understanding of these mechanisms and clinical features may improve early recognition, guide multidisciplinary management, and support safer use of immunotherapy-based combinations in patients with RCC.