Future Directions in Renal Cell Carcinoma

The final segment focuses on innovation and the expanding treatment horizon for advanced renal cell carcinoma. Ongoing studies are investigating next-generation immunotherapies, bispecific antibodies, antibody-drug conjugates, and new pathways involved in tumor resistance. These efforts aim to enhance response durability and overcome treatment resistance observed with current regimens.

Panelists note that integrating biomarkers into treatment decisions will likely refine patient selection and enable more precise sequencing of therapies. Collaborative clinical trials are key to validating these strategies and ensuring accessibility across practice settings.

The discussion concludes with optimism that continuous discovery, coupled with real-world validation, will advance outcomes and sustain the progress achieved in recent years, ultimately translating into longer survival and better quality of life for patients.

Videos

Panelists discuss emerging research directions and novel therapeutic combinations poised to shape the next generation of renal cell carcinoma management.

Recent Advances in Different Subtypes of Renal Cell Carcinoma

The conversation highlights how precision medicine is reshaping renal cell carcinoma (RCC) management. Advances in genomic and molecular profiling have revealed subtype-specific vulnerabilities that inform treatment selection. Non–clear cell variants, once underserved by clinical trials, are now receiving attention through tailored therapeutic studies.

Panelists discuss the increasing role of targeted and immune-based combinations adapted to histologic subtypes. These developments demonstrate that individualized approaches can yield meaningful responses even in rare variants, marking a shift toward more inclusive and biologically informed treatment paradigms.

Overall, the segment underscores that progress in molecular understanding is driving a more refined, evidence-based approach that transcends traditional “one-size-fits-all” treatment.

Panelists explore histology-specific and molecularly guided approaches that are expanding treatment options across renal cell carcinoma subtypes.

Adverse Event Management and Dosing of Immunotherapies and Tyrosine Kinase Inhibitors

As treatment regimens have become more potent, effective toxicity management is essential. Panelists highlight common adverse events associated with immune checkpoint blockade and tyrosine kinase inhibitors, including fatigue, diarrhea, hepatic enzyme elevation, and hypertension. Early identification and proactive management of these effects enable continued therapy and reduce interruptions.

The discussion outlines practical approaches to dose adjustments, temporary holds, and supportive measures. Coordination between oncology providers, primary care, and subspecialists ensures that patients receive comprehensive management for treatment-related complications. Regular monitoring and patient education are emphasized as key components of safe and effective care.

By standardizing toxicity protocols and fostering patient engagement, clinicians can optimize treatment adherence and outcomes, maintaining efficacy while minimizing long-term burden.

Panelists discuss strategies for recognizing, preventing, and managing toxicities associated with frontline combination regimens in advanced renal cell carcinoma.

Adjuvant Therapy Considerations in Renal Cell Carcinoma

The conversation turns to the growing role of adjuvant therapy following surgical resection in high-risk localized or locally advanced RCC. Recent trials have demonstrated that systemic treatment in this setting can delay recurrence and potentially improve long-term outcomes. Panelists highlight ongoing debates regarding patient selection, timing, and optimal duration of therapy.

Adjuvant management is guided by risk assessment, which incorporates tumor stage, histology, and performance status. Multidisciplinary collaboration ensures that patients most likely to benefit from systemic treatment are identified early. The discussion emphasizes that close surveillance remains appropriate for some patients, especially when recurrence risk is moderate or treatment tolerance is uncertain.

Panelists conclude that continued clinical research and real-world experience will refine adjuvant strategies, balancing relapse prevention with quality of life and toxicity considerations.

Panelists discuss evolving evidence supporting adjuvant therapy in renal cell carcinoma and how these findings inform clinical decision-making.

Key Clinical Trial Results for First-Line Treatments for Renal Cell Carcinoma

This discussion reviews the pivotal trials that have established current frontline standards. Studies evaluating immunotherapy and targeted therapy combinations consistently demonstrate significant improvements in overall survival, response rates, and durability of remission compared with historical controls. These findings underscore the synergistic potential of combining immune checkpoint blockade with angiogenesis inhibition.

Panelists emphasize that interpretation of results must consider patient risk stratification and trial design nuances. They highlight consistent trends showing broad benefit across favorable, intermediate, and poor-risk groups, with some regimens achieving long-term disease stabilization in subsets of patients. Importantly, safety data confirm that immune-related and vascular adverse events are predictable and manageable with established protocols.

Collectively, these clinical data validate the frontline role of combination strategies, offering a strong foundation for personalized therapy selection and ongoing innovation in advanced renal cell carcinoma (RCC).

Panelists analyze landmark clinical trial data supporting current frontline RCC therapies, focusing on response rates, progression-free survival, and overall benefit across risk groups.

Important Background Information on Advanced Renal Cell Carcinoma

The discussion begins by outlining the clinical landscape of advanced renal cell carcinoma (RCC), emphasizing that while clear cell disease remains the most common subtype, non–clear cell variants represent an important and heterogeneous group. These include papillary, chromophobe, and other rare histologies, each with distinct molecular characteristics and prognostic implications. Understanding these variations is critical for appropriate therapeutic selection and clinical trial enrollment.

Panelists explain that recent advances in tumor biology and genomic profiling have deepened insight into the drivers of RCC progression. These developments have led to a more nuanced classification system and a shift toward histology- and biomarker-guided therapy. Epidemiologic data also underscore the growing incidence of RCC worldwide and the ongoing need for improved detection and personalized management strategies.

By establishing this foundation, the conversation highlights how comprehensive understanding of RCC subtypes enables clinicians to better interpret emerging clinical data and align treatment strategies with patient-specific disease biology.

Panelists discuss the epidemiology, histologic diversity, and evolving biology of advanced renal cell carcinoma, setting the stage for modern treatment selection.

Guideline-Recommended First-Line Treatments for Renal Cell Carcinoma

This segment centers on how evidence from pivotal studies has reshaped the frontline standard of care for advanced renal cell carcinoma (RCC)RCC. Immunotherapy-based doublets and combinations with targeted agents have become the mainstay of treatment, displacing monotherapy approaches in most risk categories. The rationale for these regimens lies in their ability to produce durable responses while maintaining manageable toxicity profiles.

Panelists compare treatment algorithms across guideline bodies, noting that selection depends on clinical factors such as disease risk, performance status, and comorbidities. The discussion highlights how both immunotherapy plus targeted therapy and dual immunotherapy combinations have shown improved survival outcomes compared to traditional regimens, offering flexibility for individualized care.

Ultimately, they conclude that the evolution of combination approaches marks a major advance in frontline management, providing long-term control and quality-of-life benefits for many patients with advanced disease.

Panelists review current guideline-endorsed first-line treatment options for advanced renal cell carcinoma, emphasizing immunotherapy- and VEGF inhibitor–based combination regimens.

Dr Gruenwald on Tumor Responses With Lenvatinib Plus Pembrolizumab in Advanced RCC

Viktor Gruenwald, MD, PhD, professor, interdisciplinary genitourinary oncology, Essen University Hospital, West German Cancer Center, Clinic for Urology, Clinic for Medical Oncology, Essen, Germany, discusses key results from a post hoc analysis of the phase 3 CLEAR trial (NCT02811861) in advanced renal cell carcinoma (RCC), highlighting the clinical implications of these results.

The multicenter, open-label, randomized trial compared lenvatinib (Lenvima) plus pembrolizumab (Keytruda) with sunitinib (Sutent) for the treatment of patients with advanced RCC in the first-line. Previously reported results from the primary analysis showed that the combination improved progression-free survival outcomes and tumor shrinkage responses vs sunitinib in the overall cohort.

An exploratory analysis was conducted to assess tumor responses according to baseline metastatic characteristics from patients on study treatment at the time of the final prespecified overall survival (OS) analysis. Key baseline characteristics included the site of metastasis, number of metastatic sites, and baseline sums of diameters of target lesions.

showed that the combination of pembrolizumab and lenvatinib maintained efficacy and produced favorable tumor responses across all subgroups of interest, Gruenwald reports. The regimen's efficacy was particularly notable in patients with increased disease burden. A greater depth and breadth of tumor shrinkage was also observed in target lesions in specific organ sites (lung, lymph node, liver, and bone) for patients in the lenvatinib plus pembrolizumab arm vs the sunitinib arm. Moreover, the median duration of response was generally longer with lenvatinib plus pembrolizumab vs sunitinib. 

This information is valuable, as it helps oncologists understand the treatment's efficacy across diverse metastatic sites, ensuring a comprehensive and reliable response to treatment, Gruenwald states. The observed pattern of deep response and substantial tumor shrinkage reinforces the robustness of this combination therapy, and further supports the use of pembrolizumab and lenvatinib as a first-line standard of care in RCC, he emphasizes. Clinically, this consistency is crucial for healthcare providers when assessing and managing patients with RCC, offering insights into the treatment's effectiveness in different scenarios and contributing to informed decision-making in clinical practice, Gruenwald concludes.

Viktor Gruenwald, MD, PhD, discusses key results from a post-hoc analysis of the phase 3 CLEAR trial in advanced renal cell carcinoma.

Viktor Gruenwald, MD, PhD

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