Objective:

To synthesize contemporary evidence on neoadjuvant systemic therapies for clear cell renal cell carcinoma (ccRCC) and explore evolving treatment paradigms.

Approach:

• Literature Search: A focused literature search was performed using PubMed, Embase, and Web of Science, targeting studies on neoadjuvant therapy for RCC.
• Study Selection: Eligible publications included randomised controlled trials, systematic reviews, and prospective trials, while case reports and non-English publications were excluded.
• Evidence Organization: Evidence was organized according to study design and therapeutic approach, emphasizing prospective and multicentre investigations.

Key Findings:

• Neoadjuvant therapy may induce tumor cytoreduction and downstaging, facilitating easier surgical resection.
• Targeted therapies and immunotherapy can modulate the tumor microenvironment, enhancing immune response.
• Pathological response rates are used as surrogate markers of efficacy, but reporting standards are not yet uniform.

Interpretation:

Neoadjuvant systemic therapies for ccRCC have the potential to improve surgical outcomes and long-term oncological results through immune modulation and tumor reduction.

Limitations:

• Variability in criteria for measuring pathological responses.
• Lack of standardization in specimen preparation and reporting.

Conclusion:

Neoadjuvant therapies represent a promising strategy in the management of ccRCC, warranting further investigation and standardization in clinical trials.