Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: a joint SITC and INMC effort

Practice-changing clinical trials for novel therapeutic regimens administered in the neoadjuvant setting have been reported for multiple cancer types, bringing this treatment strategy to the forefront for patients with high-risk surgically resectable disease. Previously, tumor-type- or therapy-type-specific scoring systems were used for pathologic response assessment. The goal of this effort is to update, harmonize, and standardize the emerging system(s) for pathologic response assessment and data capture.

Leaders in pathology, oncology, and surgery, including those from the Society for Immunotherapy of Cancer's Pan-tumor Harmonization of Pathologic Response Assessment (PATHdata) efforts and the International Neoadjuvant Melanoma Consortium (INMC), convened to develop updated consensus guidelines for pathologic response assessment, including specimen handling and tissue submission, scoring, and reporting. This paper builds upon previous recommendations, which are updated based on histologic features associated with patient outcomes. Specific attention was paid to commonalities across tumor types, as well as tumor-type-specific considerations.

A revised and standardized approach to tissue submission is recommended, including total submission of tumors ≤3 cm in size for histologic analysis. Additional guidance is provided for larger tumors. Pathologic response is quantified through assessments of percentage of residual viable tumor (%RVT), necrosis, and regression. Descriptions of histologic features to be scored are provided together with a standardized reporting template. Recommendations regarding collecting additional key datapoints are also made, to allow continued, extended validation of this pan-tumor approach.

As pathologic response emerges as a surrogate endpoint for long-term clinical outcomes and to help inform adaptive adjuvant therapy decisions in routine clinical care, standardization is critical to facilitate consistent and reliable application. This pan-tumor approach to scoring and reporting supports robust stratification of patient outcomes, facilitates comparisons across clinical trials and tumor types, enhances data collection, and establishes a foundation for identifying additional, clinically meaningful %RVT cut points.