The first unified, pan-tumor guideline framework has been released for how pathologists should evaluate and score response in the neoadjuvant setting. These consensus guidelines, which were a joint effort by the Society for Immunotherapy of Cancer's (SITC) Pan-tumor Harmonization of Pathologic Response Assessment efforts and the International Neoadjuvant Melanoma Consortium (INMC), build upon prior criteria for tumor response measurements after surgery, which were first developed using immune-related criteria for lung cancer and then extended across tumor types. The updated guidelines have taken into account 5 years of real-world use and data.
The guidelines as well as a related reproducibility study were both published in the Annals of Oncology.
“Neoadjuvant therapy is rapidly expanding across cancer types, and pathologic response is emerging as a predictor of long-term survival and an important clinical trial endpoint,” stated lead author Julie Stein Deutsch, MD, Assistant Professor of Dermatology, Pathology, and Oncology, Johns Hopkins Medicine. “However, scoring systems have varied widely by tumor type, making it difficult to compare across studies or apply results reliably in practice. This unified approach establishes a common language that will benefit clinical care, research and future regulatory use.”
Background
Researchers have noted that pathologic responses to treatments, especially immunotherapy treatments, have appeared similar across cancer types, leading to the coalescing of response criteria into one set of guidelines.
“Most pathologists around the world are generalists, not tumor-type specialists,” said senior author Janis Taube, MD, Director of Dermatopathology and Co-Director of the Bloomberg~Kimmel Institute Tumor Microenvironment Laboratory. “Switching between multiple scoring systems is inefficient and can lead to inconsistent reporting. Our findings support a pan-tumor system—and importantly, no existing tumor-specific system outperforms this unified approach in predicting patient outcomes.”
Leaders across the fields of pathology, oncology, and surgery came together to update, harmonize, and standardize pathologic response assessments for patients with cancer being treated with neoadjuvant therapy. They aimed to create one set of updated consensus guidelines that would apply across tumor types, rather than tumor type– or therapy type–specific response criteria.
Guidelines
Within the updated guidelines is a recommendation for a standardized approach to tissue submission based on size. A tumor/tumor bed 3 cm or less is recommended to be submitted in its entirety; if the tumor is larger than 3 cm, at a minimum one complete cross-section of tumor/tumor bed should be submitted from the longest dimension of the tumor for embedding, as well as the interface of the tumor with surrounding tissue when possible.
Quantification and scoring for pathologic response to neoadjuvant treatment for both the primary tumor and the lymph node components should be assessed based on the percentage of residual viable tumor, necrosis, and regression.
Reproducibility Study
Also steering the establishment of these updated guidelines was a multi-institutional, international study led by SITC for evaluating interobserver pathologist variability among response assessments by tumor type, anatomic location, and specimen type in using the updated pan-tumor criteria.
Fourteen participating pathologists were taught about the updated response criteria scoring through online lectures; they then assessed 42 specimens from across 12 tumor types to analyze residual viable tumor, necrosis, and regression measurements for the updated criteria. The researchers also surveyed the participants about their use of and challenges with the new response assessments.
They found the pathologic response criteria scoring to be highly reproducible using the new pan-tumor system. Correlation coefficients between the participants were above 0.8 for residual viable tumor, necrosis, and regression measurements. Subset analyses also showed strong reproducibility, with intraclass correlation coefficients all above 0.86.
“Reproducibility is essential,” Dr. Deutsch said. “Different pathologists must arrive at similar scores if these metrics are going to guide patient care and clinical trials. Our training materials make that possible, and we are partnering with SITC to disseminate these resources.”
The survey responses also helped to bring to light potential barriers to implementation and helped the researchers come up with strategies to overcome these barriers.
Going forward, the researchers plan to refine the thresholds for residual viable tumor for specific tumor types.
DISCLOSURE: The work was supported by The Mark Foundation for Cancer Research, the Bloomberg~Kimmel Institute for Cancer Immunotherapy, the Ontario Institute for Cancer Research, National Institutes of Health/National Cancer Institute, The National Institutes of Health Specialized Programs of Research Excellence, the University of Texas MD Anderson Melanoma Moon Shots Program, LUNGevity Foundation, the Dermatology Foundation, Australia’s National Health and Medical Research Council, University of Sydney Medical Foundation, the Michael and Patricia Booker Melanoma Research Endowment, and the John M. Skibber Endowed Professorship. For full disclosures of the study authors, visit annalsofoncology.org.
