Developing biomarkers and methods of risk stratification: Consensus statements from the International Kidney Cancer Symposium North America 2024 Think Tank.

Accurate prognostication and personalized treatment selection remain major challenges in kidney cancer. This consensus initiative aimed to provide actionable expert guidance on the development and clinical integration of prognostic and predictive biomarkers and risk stratification tools to improve patient care and guide future research. A modified Delphi method was employed to develop consensus statements among a multidisciplinary panel of experts in urologic oncology, medical oncology, radiation oncology, pathology, molecular biology, radiology, outcomes research, biostatistics, industry, and patient advocacy.

Risk Factors for First-Year Recurrence in Patients With Synchronous Metastatic Renal Cell Carcinoma Undergoing Cytoreductive Nephrectomy and Complete Metastasectomy.

Purpose: Patients with metastatic renal cell carcinoma (mRCC) with oligometastatic disease can achieve radiographic disease-free (M1 NED) status after cytoreductive nephrectomy and concurrent complete metastasectomy. This study aimed to evaluate outcomes and identify risk factors associated with metastatic recurrence and overall survival in patients with mRCC M1 NED.

Materials And Methods: Patients with synchronous mRCC who were M1 NED after cytoreductive nephrectomy and concurrent complete metastasectomy from 4 institutions (2010-2020) were identified.

Psammomatous Calcifications Identified in Targeted Needle Biopsies and Radical Prostatectomy From IDH1 Mutant Prostatic Adenocarcinoma: Case Report and Literature Review.

IDH1 mutant prostatic adenocarcinoma represents a small fraction of prostate cancer with distinct epigenetic changes, characterized by genome-wide DNA hypermethylation. Recently, prostatic adenocarcinoma with intratumoral psammomatous calcifications was found to frequently harbors IDH1 R132 mutations. However, the association with IDH1 hotspot mutations and psammomatous calcifications in prostate cancer remains controversial.

Vigorous physical activity as a potential environmental risk factor in renal medullary carcinoma.

Purpose: Renal medullary carcinoma (RMC) is a rare but aggressive kidney cancer affecting young individuals with sickle hemoglobinopathies. Prior retrospective case-control and mouse modeling studies suggest a mechanism linking vigorous intensity physical activity to increased RMC risk in individuals with sickle hemoglobinopathies. This study aimed to prospectively investigate the association between vigorous intensity exercise and RMC.

Statins Are Not Associated with Improved Bladder Cancer Outcomes in Patients with Early-Stage Bladder Cancer Treated with BCG Immunotherapy.

: Statins are commonly used cholesterol-lowering drugs with evidence of additional chemoprotective and immunomodulatory effects resulting from the inhibition of DNA replication, cell proliferation, and TH1-cell inhibition. There are conflicting reports regarding the potential benefit of concurrent statin treatment on non-muscle invasive bladder cancer (NMIBC) and specifically on intravesical Bacillus Calmette-Guerin (BCG) outcomes. We therefore aimed to analyze the effects of concurrent BCG and statin use in patients with NMIBC.

Immune checkpoint inhibitors plus debulking surgery for patients with metastatic renal cell carcinoma: clinical outcomes and immunological correlates of a prospective pilot trial.

Surgical removal of primary tumors reverses tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT), is not understood. We report the first prospective, pilot, non-comparative clinical trial (NCT02210117) to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma.

Differentiating between renal medullary and clear cell renal carcinoma with a machine learning radiomics approach.

Background: The objective of this study was to develop and validate a radiomics-based machine learning (ML) model to differentiate between renal medullary carcinoma (RMC) and clear cell renal carcinoma (ccRCC).

Methods: This retrospective Institutional Review Board -approved study analyzed CT images and clinical data from patients with RMC (n = 87) and ccRCC (n = 93). Patients without contrast-enhanced CT scans obtained before nephrectomy were excluded.

A Call for a Neoadjuvant Kidney Cancer Consortium: Lessons Learned from Other Cancer Types.

Neoadjuvant systemic treatment strategies have improved outcomes in several solid tumour types. This success has not yet been replicated in renal cell carcinoma (RCC). A consensus and international collaboration are urgently needed for the development of adaptive perioperative immunotherapy strategies for patients with RCC at high risk of recurrence.

Safety outcomes and immunological correlates in a prospective clinical trial of immune checkpoint therapy plus debulking surgery for patients with metastatic renal cell carcinoma.

Surgical removal of primary tumors was shown to reverse tumor-mediated immune suppression in pre-clinical models with metastatic disease. However, how cytoreductive surgery in the metastatic setting modulates the immune responses in patients, especially in the context of immune checkpoint therapy (ICT)-containing treatments is not understood. Here, we report the first prospective, non-comparative clinical trial to evaluate the feasibility, clinical benefits, and immunologic changes of combining three different ICT-containing strategies with cytoreductive surgery or biopsy for patients with metastatic clear cell renal cell carcinoma (mccRCC).

Paraneoplastic Resolution Holds Prognostic Utility in Patients with Metastatic Renal Cell Carcinoma.

The presence of paraneoplastic syndromes (PNS) in patients with renal cell carcinoma (RCC) is associated with worse survival; however, little is known about whether resolution of PNS after intervention has any prognostic value. We sought to determine if resolution of PNS by one year after cytoreductive nephrectomy was significantly associated with improved overall survival (OS) and cancer-specific survival (CSS). We retrospectively reviewed a prospectively maintained nephrectomy database for patients with any histology metastatic RCC (mRCC) who underwent nephrectomy between 2000 and 2022.

Impact of postprogression therapies on overall survival: Recommendations from the 2023 kidney cancer association think tank meeting.

Modern advances in systemic and localized therapies for patients with renal cell carcinoma (RCC) have significantly improved patients' outcomes. If disease progression occurs after initial treatment, clinicians often have multiple options for a first salvage therapy. Because salvage and initial treatments both may affect overall survival time, and they may interact in unanticipated ways, there is a growing need to determine sequences of initial therapy and first salvage therapy that maximize overall survival while maintaining quality of life.

Challenges and Considerations in Modern Adjuvant Therapy Trials in Renal Cell Carcinoma: A Call to Power.

Identification of effective adjuvant therapies for renal cell carcinoma remains challenging despite the development of immune checkpoint inhibitors. Enhancement of the design of trials of adjuvant therapy by focusing on populations with the highest risk and increasing the sample size is essential for reliable assessments of therapeutic efficacy.

Non-Metastatic Clear Cell Renal Cell Carcinoma Immune Cell Infiltration Heterogeneity and Prognostic Ability in Patients Following Surgery.

Predicting which patients will progress to metastatic disease after surgery for non-metastatic clear cell renal cell carcinoma (ccRCC) is difficult; however, recent data suggest that tumor immune cell infiltration could be used as a biomarker. We evaluated the quantity and type of immune cells infiltrating ccRCC tumors for associations with metastatic progression following attempted curative surgery. We quantified immune cell densities in the tumor microenvironment and validated our findings in two independent patient cohorts with multi-region sampling to investigate the impact of heterogeneity on prognostic accuracy.

Shorter Ureters Lead to Fewer Strictures Following Cystectomy and Urinary Diversion.

Objective: To identify the impact of length of distal ureteral resection on the risk of benign uretero-enteric anastomotic stricture (UEAS) formation following cystectomy and urinary diversion.

Methods: A database of patients who underwent cystectomy and urinary diversion from 2015 to 2022 was analyzed. Distal ureteral resections were sent for final pathology.

Management of stage 1 renal cell cancer in patients immunosuppressed for organ transplantation or autoimmune disease.

Objective: To describe the treatment and outcomes of patients who are medically immunosuppressed due to prior organ transplantation or autoimmune disease with clinical T1 renal cell carcinoma (cT1).

Methods: An institutional database of patients treated for RCC was queried for patients with cT1 RCC and on chronic medical immunosuppression at the time of RCC diagnosis. The outcomes for patients undergoing (1) surgery, (2) ablation, or 3) active surveillance (AS) are described.

Impact of Agent Orange Exposure on Non-muscle Invasive Bladder Cancer Outcomes.

Objective: To explore the effect of Agent Orange (AO) exposure on bladder cancer (BCa) outcomes in patients receiving Bacillus Calmette-Guérin (BCG) for non-muscle invasive BCa (NMIBC).

Methods: We retrospectively examined the association between AO exposure in patients with NMIBC in national veterans affairs databases who were being treated with BCG. Patients were diagnosed with NMIBC from 2000 to 2010 with follow-up through 2018.

Contemporary Patients Have Better Perioperative Outcomes Following Cytoreductive Nephrectomy: A Multi-institutional Analysis of 1272 Consecutive Patients.

Objective: To evaluate factors associated with perioperative outcomes in a multi-institutional cohort of patients treated with cytoreductive nephrectomy (CN).

Methods: Data were analyzed for metastatic renal cell carcinoma patients treated with CN at 6 tertiary academic centers from 2005 to 2019. Outcomes included: Clavien-Dindo complications, mortality, length of hospitalization, 30-day readmission rate, and time to systemic therapy.

The Selection for Cytoreductive Nephrectomy (SCREEN) Score: Improving Surgical Risk Stratification by Integrating Common Radiographic Features.

Background: Careful patient selection is critical when considering cytoreductive nephrectomy (CN) for metastatic renal cell carcinoma (mRCC) but few studies have investigated the prognostic value of radiologic features that measure tumor burden.

Objective: To develop a prognostic model to improve CN selection with integration of common radiologic features with known prognostic factors associated with mortality in the first year following surgery.

Design, Settings, And Participants: Data were analyzed for consecutive patients with mRCC treated with upfront CN at five institutions from 2006 to 2017.

Understanding and integrating cytoreductive nephrectomy with immune checkpoint inhibitors in the management of metastatic RCC.

Cytoreductive nephrectomy became accepted as standard of care for selected patients with metastatic renal cell carcinoma (mRCC) because of improved survival observed in patients treated with cytoreductive nephrectomy in combination with interferon-α in two randomized clinical trials published in 2001. Over the past two decades, novel systemic therapies have shown higher treatment response rates and improved survival outcomes compared with interferon-α. During this rapid evolution of mRCC treatments, systemic therapies have been the primary focus of clinical trials.

Neddylation inhibition sensitises renal medullary carcinoma tumours to platinum chemotherapy.

Background: Renal medullary carcinoma (RMC) is a highly aggressive cancer in need of new therapeutic strategies. The neddylation pathway can protect cells from DNA damage induced by the platinum-based chemotherapy used in RMC. We investigated if neddylation inhibition with pevonedistat will synergistically enhance antitumour effects of platinum-based chemotherapy in RMC.

SMARCB1 regulates the hypoxic stress response in sickle cell trait.

Renal medullary carcinoma (RMC) is an aggressive kidney cancer that almost exclusively develops in individuals with sickle cell trait (SCT) and is always characterized by loss of the tumor suppressor . Because renal ischemia induced by red blood cell sickling exacerbates chronic renal medullary hypoxia in vivo, we investigated whether the loss of SMARCB1 confers a survival advantage under the setting of SCT. Hypoxic stress, which naturally occurs within the renal medulla, is elevated under the setting of SCT.