Feasibility and Characterization of Immune-related Pathologic Response Criteria in Renal Cell Carcinoma

Pathologic assessment of treatment response in renal cell carcinoma (RCC) after systemic combination therapy is increasingly relevant, yet traditional reporting methods fail to capture unique immune-mediated changes, and a lack of standardized reporting recommendations has led to discordant clinical trial definitions. We evaluated the feasibility and implementation of immune-related pathologic response criteria (irPRC), recently endorsed by the International Neoadjuvant Kidney Cancer Consortium, in a retrospective cohort of 35 patients (37 tumors). Application of irPRC was feasible in all cases and identified major pathologic response in 35% of the tumors. Tumor bed evaluation based on irPRC components revealed substantial heterogeneity, highlighting the limitations of relying on tumor fraction alone. All patients (N = 11) experiencing recurrence within 6 mo of surgery exhibited necrosis-predominant tumor beds and a complete absence of tissue repair features, suggesting an area for additional research. In addition, radiographic response correlated poorly with pathologic findings; nearly one-third of major pathologic responders lacked significant radiographic improvement. These findings support the feasibility of irPRC in RCC and underscore the limitations of current radiographic and traditional pathologic response assessments. Broader adoption of standardized immune-related pathologic response frameworks may improve consistency in reporting and better reflect underlying tumor biology in clinical research.