Assessing pathological response to neoadjuvant therapy in renal cell carcinoma: a systematic review and guidelines for sampling and reporting standards from the International Neoadjuvant Kidney Cancer Consortium.

Pathological response is a surrogate marker of efficacy of neoadjuvant therapy in various tumour types, but there is no consensus on reporting pathological response for renal cell carcinoma. We aimed to assess the status of pathological response reporting in renal cell carcinoma and develop a recommendation on tissue preparation and response reporting for neoadjuvant treatment. We conducted a systematic review of publications on the PubMed and Web of Science databases to identify manuscripts reporting response to pre-surgical therapy in renal cell carcinoma. 119 eligible papers were identified. Only five (4%) studies included details of how pathological response had been assessed. Qualitative statements on residual tumour were common (55 [46%] studies), but only eight (7%) studies used a quantitative assessment of pathological response. Guidelines for tissue preparation and pathological response reporting were reviewed at an international workshop held at the Netherlands Cancer Institute in October, 2024, and further developed through expert discussions. To assess neoadjuvant pathological response, nephrectomy specimens should be sampled with the use of a standardised baseline approach with consideration for more extensive sampling. Microscopic assessment should quantify the residual viable tumour in 10% intervals and greatest linear extent. Clinical details, including the neoadjuvant therapy received, should accompany the pathological assessment. In this systematic review, we describe a standardised method for assessment and reporting pathological response, initially intended for use in clinical trials or research settings. These guidelines will help investigators to assess whether the degree of pathological response is linked to survival outcomes and will inform future standard reporting practices.