Towards a standard for evaluating pathological response in neoadjuvant kidney cancer trials

This third blog in our series on International Neoadjuvant Kidney Cancer Consortium (INKCC), outlines the first guidelines published by the consortium. One area in which the INKCC Delphi process could not identify consensus was in pathological response criteria – researchers do not agree on how to define tumour response to neoadjuvant therapy but unanimously agreed that a standardised reporting of pathological response is needed to enable comparison between studies.

This week, in Lancet Oncology, INKCC members, including UMVI Translational Lead Dr James Jones, make recommendations on pathological response reporting, the ‘INKCC Criteria’, that they hope will become standard across neoadjuvant kidney cancer trials.

With neoadjuvant therapy, patients receive treatment quickly and before their primary treatment (usually surgery). Interventions at this stage may help to reduce the tumour size and/or provide information about how the tumour responds to treatment, guiding decisions about next steps for the patient. Pathological response is used to indicate the efficacy of neoadjuvant therapy across multiple tumour types. However, there is currently no standardised reporting of pathological response for renal cell carcinoma (RCC), constraining understanding of the efficiency of this type of treatment.

A systematic review of manuscripts on the topic of pre-surgical therapy in RCC identified 119 eligible papers, which were analysed to identify pathological response methodology. The authors concluded that pathological response in RCC literature is ‘highly variable’, and the reporting approaches and threshold criteria characterised by a lack of supporting evidence.

After consultation with experts at an international workshop at the Netherlands Cancer Institute (NKI) and follow on discussions with clinicians and patient advocates, the authors make recommendations across five domains for assessing pathological response. They also highlight the importance of preserving specimens for future research. The guidelines also account for RCC’s specific and challenging features, for example its heterogeneity and high levels of necrotic (dead) tissue found in some cases.

Senior author, Dr James Jones, said, “The previous lack of consensus on pathological response assessment within INKCC was reflected in the findings of our systematic review. It has been fantastic to work with experts from INKCC in different countries to develop these first consensus guidelines to address this problem in RCC. We hope that researchers will adopt these recommendations as the initial step to building a unified landscape in neoadjuvant RCC research. If pathological response to neoadjuvant therapy can be linked to survival outcomes, this would be a valuable finding for clinical trials and the standard care of patients with kidney cancer”.

Read the full paper here:

Blackmur et al . (2025). Assessing Pathological Response to Neoadjuvant Therapy in Renal Cell Carcinoma: A Systematic Review and Guideline for Sampling and Reporting Standards from the International Neoadjuvant Kidney Cancer Consortium DOI: 10.1016/S1470-2045(25)00345-6