1943P Updated pan-tumor guidelines for neoadjuvant scoring of pathologic response: A joint SITC and INMC effort

Practice-changing clinical trials have recently been reported for multiple tumor types, bringing neoadjuvant therapy (NAT), particularly immunotherapy, to the forefront for patients with surgically resectable disease. Many of these studies used legacy systems to assess pathologic response for patients receiving chemotherapy or scoring systems designed a priori. The goal of this effort is to update, harmonize, and when possible, standardize the emerging system(s) for pathologic response assessment.

We developed revised guidelines for assessing pathologic response to NAT (immunotherapy, targeted therapy, chemotherapy, and combinations), based on correlating histologic features with patient outcomes. Members of the International Neoadjuvant Melanoma Consortium and Society for Immunotherapy of Cancer’s PATHdata, representing pathologists, and surgical and medical oncologists, developed updated consensus guidelines for specimen handling and pathologic response reporting. Specific focus was paid to commonalities across tumor types, as well as instances where individual tumor types warrant distinct consideration.

This guideline includes updates to previously published recommendations (Cottrell, Ann Oncol, 2018 and Tetzlaff, Ann Oncol 2018). It describes an updated approach to gross sampling, with a 3 cm cutoff for complete tumor submission for histologic analysis. Quantifying changes in tumor area in NAT-treated tumor specimens is achieved through assessments of %of residual viable tumor (RVT), necrosis, and regression bed, which together total 100%. Categories of pathologic response and histologic features to be scored are provided together with guidelines for reporting the full spectrum of %RVT to further validate this pan-tumor approach and identify clinically meaningful cutpoints. Strategies for addressing common histologic challenges are also described.

Outcomes data from recent clinical trials have allowed for the correlation of key pathologic features with EFS. Pathologic response assessment can largely be standardized across tumor types, facilitating the comparison of therapeutic regimens across clinical trials and between indications.