Systemic therapy for non-clear cell renal cell carcinomas: A systematic review

Area of Science:

• Oncology
• Genitourinary Cancers
• Translational Research

Background:

• Renal cell carcinoma (RCC) is the most common kidney cancer, with clear cell RCC as the predominant subtype.
• Non-clear cell RCC (nccRCC) comprises a significant proportion of cases and presents unique treatment challenges due to diverse histological subtypes.
• Optimal therapeutic strategies for nccRCC remain uncertain due to limited high-quality evidence.

Purpose of the Study:

• To systematically review and evaluate the efficacy of systemic therapies in various non-clear cell renal cell carcinoma subgroups.
• To assess the current evidence for targeted agents, immunotherapy, and combination therapies in nccRCC treatment.

Main Methods:

• A comprehensive literature search was conducted using PubMed and Clinicaltrials.gov from 2010 to 2024.
• The review focused on clinical trials and treatment outcomes for non-clear cell renal cell carcinoma.
• Studies were analyzed to identify effective systemic therapies and treatment strategies for different nccRCC subtypes.

Main Results:

• Targeted agents like tyrosine kinase inhibitors (TKIs) and mTOR inhibitors demonstrate efficacy across nccRCC subtypes.
• Immunotherapy, including immune checkpoint inhibitors (e.g., nivolumab, pembrolizumab), shows promising anti-tumor activity.
• Combination therapies, particularly those incorporating immunotherapy, have yielded favorable outcomes. Targeting the c-MET pathway is effective in specific papillary RCC cases.

Conclusions:

• Systemic therapy for nccRCC is complex and evolving, with combination therapies and immunotherapies showing positive results.
• Immune checkpoint inhibitors and targeted pathway inhibition represent key advancements in nccRCC treatment.
• Further research is essential to establish optimal treatment strategies for distinct nccRCC histological subtypes and improve patient outcomes.