High circulating IL-6/IL-8 is associated with intratumoral myeloid contexture and poor outcomes in advanced renal cell carcinoma patients treated with PD-1 blockade.

Purpose: The phase II NIVOREN GETUG-AFU-26 study assessed the safety and activity of nivolumab in a real-world population with pretreated advanced clear cell renal cell carcinoma (aRCC). A comprehensive translational research program was conducted including blood and tissue-based analyses. Herein we assessed circulating factors at baseline, their association with intratumoral immune contexture and outcomes.

Induction of tertiary lymphoid structures in tumor microenvironment to improve anti-tumoral immune checkpoint blockade efficacy.

Immune checkpoint blockade (ICB) have revolutionized medical oncology, with the occurrence of cures in situations regarded as palliative. However, most patients develop resistance and the selection of responders remains difficult. The search for predictive biomarkers for immunotherapy has revealed that tertiary lymphoid structures (TLS) in the tumor microenvironment (TME) may be indicative of treatment effectiveness, since they may reflect the presence of an immune infiltrate with an anti-tumor effect.

[Intercontinental Multidisciplinary Oncology Videoconferencing between the South Pacific and the French mainland: Reasons for medical evacuation after more than 2000 cases of cancers discussed].

Introduction: Disparities in care between the French mainland and overseas territories are responsible for unequal access to innovative and specialized care, leading to an increased death risk for cancer patients. Since 2019, a multidisciplinary consultation meeting (RCP Pacifique) by videoconference between French Polynesia (Pf), New Caledonia (NC) and mainland France, facilitates access to medical expertise and limits the use of medical evacuations (EVASAN).

Methods: We retrospectively analyzed all files discussed in the RCP Pacifique between 2019 and 2024 to report demographic data, reasons for EVASAN and post-EVASAN developments.

Activity of lenvatinib-based therapy in previously treated patients with metastatic renal cell carcinoma: A European multicenter study (LENVA-LAT).

Background And Objective: Lenvatinib's activity after immune checkpoint inhibitors (ICI) combination therapy in renal cell carcinoma (RCC) remains unknown. We aimed to describe the real-world outcomes of patients with metastatic RCC (mRCC) treated with lenvatinib after failure of the prior standard of care.

Methods: Multicenter retrospective study including patients with mRCC treated with lenvatinib-based therapies beyond first-line therapy between 2020 and 2024.

The effect of tumor downsizing on surgical complexity during nephrectomy after immune checkpoint inhibitors for metastatic renal cell carcinoma.

Purpose: Immune Checkpoints Inhibitors (ICI) have changed the therapeutic landscape of metastatic renal cell carcinoma first-line treatment with complete response (CR) at metastatic sites observed in 10 to 15% of cases. Delayed nephrectomy could be discussed for patients having a clinical benefit from immunotherapy-based treatment. However, it is unclear whether prior immunotherapy exposure adversely influences the complexity of surgery.

Blood-based circulating biomarkers for prediction of immune-checkpoint inhibitors efficacy in renal cell carcinoma.

Immune checkpoint inhibitors (ICI)-based combinations have become the standard first-line treatment for advanced clear cell renal cell carcinoma (ccRCC). Despite significant improvements in survival and the achievement of sustained long-term responses, a subset of patients remains refractory to ICI, and most will eventually develop resistance. Thus, identifying predictive biomarkers for ICI efficacy and resistance is essential for optimizing therapeutic strategies.

Metastatic renal cell carcinoma with occult primary: a multicenter prospective cohort.

Metastatic carcinoma of presumed renal origin (rCUP) has recently emerged as a new entity within the heterogeneous entity of Cancers of Unknown Primary (CUP) but their biological features and optimal therapeutic management remain unknown. We report the molecular characteristics and clinical outcome of a series of 25 rCUP prospectively identified within the French National Multidisciplinary Tumor Board for CUP. This cohort strongly suggests that rCUP share similarities with common RCC subtypes and benefit from renal-tailored systemic treatment.

Une nouvelle place pour les biomarqueurs circulants dans le cancer du rein en 2024 ?

A new role for biomarkers circulating in kidney cancer in 2024?

The current landscape of stereotactic body radiation therapy for metastatic castration-resistant prostate cancer.

Background: The onset of castration-resistance is associated with dismal outcomes in patients with prostate cancer (PCa). Metastasis directed therapy has been investigated in multiple disease settings and may improve outcomes in selected patients. Our systematic review aims to summarize evidence with stereotactic body radiotherapy (SBRT) in castration-resistant prostate cancer (CRPC).

Activity of Lutetium-177 Prostate-specific Membrane Antigen and Determinants of Outcomes in Patients with Metastatic Castration-resistant Prostate Cancer Previously Treated with Cabazitaxel: The PACAP Study.

Background: Both cabazitaxel and lutetium-177 prostate-specific membrane antigen (Lu-PSMA) improve survival in metastatic castration-resistant prostate cancer (mCRPC) after an androgen receptor pathway inhibitor and docetaxel, but there are limited data regarding Lu-PSMA activity after cabazitaxel.

Objective: To assess the activity of Lu-PSMA and determinants of outcomes after cabazitaxel in mCRPC.

Design, Setting, And Participants: A retrospective analysis was conducted of consecutive mCRPC patients from eight European centers treated with Lu-PSMA after cabazitaxel.

B cells and the coordination of immune checkpoint inhibitor response in patients with solid tumors.

Immunotherapy profoundly changed the landscape of cancer therapy by providing long-lasting responses in subsets of patients and is now the standard of care in several solid tumor types. However, immunotherapy activity beyond conventional immune checkpoint inhibition is plateauing, and biomarkers are overall lacking to guide treatment selection. Most studies have focused on T cell engagement and response, but there is a growing evidence that B cells may be key players in the establishment of an organized immune response, notably through tertiary lymphoid structures.

Development of Novel Models of Aggressive Variants of Castration-resistant Prostate Cancer.

Background: Genomic studies have identified new subsets of aggressive prostate cancer (PCa) with poor prognosis (eg, neuroendocrine prostate cancer [NEPC], PCa with DNA damage response [DDR] alterations, or PCa resistant to androgen receptor pathway inhibitors [ARPIs]). Development of novel therapies relies on the availability of relevant preclinical models.

Objective: To develop new preclinical models (patient-derived xenograft [PDX], PDX-derived organoid [PDXO], and patient-derived organoid [PDO]) representative of the most aggressive variants of PCa and to develop a new drug evaluation strategy.

Safety and efficacy of nivolumab in elderly patients with metastatic clear cell renal cell carcinoma: Analysis of the NIVOREN GETUG-AFU 26 study.

Introduction: Immune checkpoint inhibitors are standard of care in metastatic renal cell carcinoma but their activity and safety in elderly patients is insufficiently explored. We evaluated outcomes of elderly patients with mRCC treated with nivolumab in the GETUG-AFU 26 NIVOREN phase 2 trial (NCT03013335) and conducted exploratory circulating biomarker analyses.

Methods: Patients with mRCC were treated with nivolumab after at least one antiangiogenic therapy.

Comprehensive analyses of immune tumor microenvironment in papillary renal cell carcinoma.

Background: Papillary renal cell carcinoma (pRCC) is the most common non-clear cell RCC, and associated with poor outcomes in the metastatic setting. In this study, we aimed to comprehensively evaluate the immune tumor microenvironment (TME), largely unknown, of patients with metastatic pRCC and identify potential therapeutic targets.

Methods: We performed quantitative gene expression analysis of TME using Microenvironment Cell Populations-counter (MCP-counter) methodology, on two independent cohorts of localized pRCC (n=271 and n=98).

Efficacy and safety of cabozantinib rechallenge in metastatic renal cell carcinoma: A retrospective multicentric study.

Background: Despite metastatic renal cell carcinoma (mRCC) expanded treatment options, disease progression ultimately occurs for most patients. Rechallenge may be a compelling strategy in a refractory setting. Cabozantinib is the standard of care in first and later lines of therapy, but its activity in rechallenge is unknown.

Impact of First Line Antiangiogenic Therapy Duration on Nivolumab Outcome in Metastatic Renal Cell Carcinoma Patients Treated in the GETUG-AFU 26 NIVOREN.

Background: In metastatic renal clear cell carcinoma (ccRCC), vascular endothelial growth factor receptor (VEGFR) and immune checkpoint are 2 main therapeutic targets. We investigated the impact of duration exposure to antiangiogenic on immunotherapy clinical outcomes in metastatic ccRCC.

Methods: Patients from NIVOREN trial who received nivolumab after only 1 prior antiangiogenic therapy were included.

Circulating and Intratumoral Immune Determinants of Response to Atezolizumab plus Bevacizumab in Patients with Variant Histology or Sarcomatoid Renal Cell Carcinoma.

Renal cell carcinoma (RCC) of variant histology comprises approximately 20% of kidney cancer diagnoses, yet the optimal therapy for these patients and the factors that impact immunotherapy response remain largely unknown. To better understand the determinants of immunotherapy response in this population, we characterized blood- and tissue-based immune markers for patients with variant histology RCC, or any RCC histology with sarcomatoid differentiation, enrolled in a phase II clinical trial of atezolizumab and bevacizumab. Baseline circulating (plasma) inflammatory cytokines were highly correlated with one another, forming an "inflammatory module" that was increased in International Metastatic RCC Database Consortium poor-risk patients and was associated with worse progression-free survival (PFS; P = 0.

Triplet Strategies in Metastatic Clear Cell Renal Cell Carcinoma: A Worthy Option in the First-Line Setting?

Significant strides have been made in the frontline treatment of patients with advanced clear cell renal cell carcinoma (ccRCC). There are multiple standard-of-care doublet regimens consisting of either the combined dual immune checkpoint inhibitors, ipilimumab and nivolumab, or combinations of a vascular endothelial growth factor receptor tyrosine kinase inhibitor and an immune checkpoint inhibitor. Currently, there is an emergence of clinical trials examining triplet combinations.