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BACKGROUND: Immune checkpoint inhibitors (ICPIs) are widely used in treating metastatic renal cell carcinoma (RCC). Cytoreductive nephrectomy (CN) forms part of multimodality treatment in advanced disease, however there is no prospective evidence for its use in the ICPI era. Trials of neoadjuvant ICPIs in RCC are underway; understanding the anticipated effect of ICPIs on the primary tumour may help clinical decision making in both localised and advanced settings. METHODS: A systematic search (PubMed, Web of Science, clinicaltrials.gov) of English literature from 2012 to 2022 was performed according to PRISMA guidelines. 2,398 records were identified, 54 were included in the analysis. RESULTS: In the metastatic setting, response in the primary tumour (≥30% reduction in size) is seen in 33–56% of patients treated with dual ICPI or ICPI + VEGFR-TKI. Pathological complete response rates were 14% for patients undergoing CN after a period of ICPI therapy. In the neoadjuvant setting there is a single published trial of VEGFR-TKI + ICPI, 30% of patients had a≥30% reduction in size of the primary. This appears superior to single agent ICPI. Grade 3 adverse event rates are comparable to the metastatic setting. CONCLUSIONS: A period of ICPI combination therapy followed by nephrectomy may be considered for selected patients as a strategy to manage metastatic disease. In the neoadjuvant setting, it is not clear whether ICPI + VEGFR-TKI is superior to VEGFR-TKI alone. There is minimal data on whether either CN after ICPI in metastatic patients, or neoadjuvant ICPI therapy for localised disease, improves long term survival.

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