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

BackgroundPractice-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.MethodsWe 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.ResultsThis 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.ConclusionsOutcomes 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.Legal entity responsible for the studyThe authors.FundingHas not received any funding.DisclosureJ.S. Deutsch: Financial Interests, Institutional, Research Funding: Bristol Myers Squibb. A. Cimino-Mathews: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb. T.R. Cottrell: Financial Interests, Institutional, Research Funding: Janssen. P. Fiset: Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Board: Astellas, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, EMD Serrano, Incite, Merck, Novartis, Pfizer, Precision Rx-Dx, Roche; Financial Interests, Institutional, Research Funding: Astellas, AstraZeneca, Bristol Myers Squibb, Merck. J.E. Gershenwald: Financial Interests, Personal, Other, consultant, advisory board, scientific advisory board: Merck; Financial Interests, Personal, Other, consultant: Regeneron; Financial Interests, Personal, Royalties, author/coauthor of several melanoma chapters for this online clinical resource: UpToDate; Financial Interests, Personal, Other, I am on the scientific advisory committee for two international randomized clinical trials in melanoma: Merck; Non-Financial Interests, Leadership Role, Chair, executive committee (voluntary position)Overall AJCC Vice Chair (voluntary position): American Joint Committee on Cancer (AJCC); Non-Financial Interests, Other, Member, ACS Cancer Surgery Standards Program (CSSP) executive committee - voluntary position: American College of Surgeons (ASC); Non-Financial Interests, Advisory Role, Member, medical advisory panel (voluntary); prior Vice-Chair and current Chair, MRA Grant Review Committee (voluntary): Melanoma Research Alliance (MRA). G.V. Long: Financial Interests, Personal, Other, Consultant Advisor: Agenus Inc, Amgen Inc, Array Biopharma Inc, AstraZeneca UK Limited, Bayer Healthcare Pharmaceuticals, BioNTech SE, Boehringer Ingelheim International GmbH, Bristol Myers Squibb, Evaxion Biotech A/S, Hexal AG, Highlight Therapeutics S.L., IOBiotech, Immunocore Ireland Limited, Innovent Bioilogics USA Inc, Merck Sharp & Dohme, Novartis Pharma AG, PHMR Limited, Pierre Fabre, Regeneron Pharmaceuticals Inc, Scancell Limited, SkylineDX B.V.; Non-Financial Interests, Principal Investigator, GL is PI on over 30 clinical trials: GL is PI on over 30 clinical trials. R.F. Salgado: Financial Interests, Personal, Advisory Board: Roche, BMS, Exact Sciences, Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Invited Speaker: Daiichi Sankyo, AstraZeneca; Financial Interests, Personal, Funding, Roche funded personally the assessment of immune-markers in a research study. This was in 2019.: Roche; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Funding: Puma Biotechnology. C. Schürch: Financial Interests, Institutional, Research Funding: Enable Medicine; Financial Interests, Personal, Advisory Board: Enable Medicine; Financial Interests, Personal, Stocks/Shares: Enable Medicine. L. Sholl: Financial Interests, Institutional, Research Funding: Bristol Myers Squibb, Genentech; Financial Interests, Personal, Advisory Board: Genentech, Lily, AstraZeneca. S. Signoretti: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, AstraZeneca, Exelixis; Financial Interests, Personal, Advisory Board: Merck, AstraZeneca, Bristol Myers Squibb, CRISPR Threapeutics AG, AACR, NCI; Financial Interests, Personal, Licencing Fees: Biogenex. M. Tetzlaff: Financial Interests, Institutional, Advisory Role: Merck. B. van de Wiel: Non-Financial Interests, Advisory Role, no activities in last two years.: BMS. X. Xu: Financial Interests, Personal, Stocks or ownership: Curebiotech, Inc, TLR Biosciences, Exio Biosciences; Financial Interests, Institutional, Research Funding: Incyte Corporation. R.A. Scolyer: Financial Interests, Personal, Advisory Board: SkylineDx BV, IO Biotech ApS, MetaOptima Technology Inc., F. Hoffmann-La Roche Ltd, Evaxion, Provectus Biopharmaceuticals Australia, Qbiotics, Novartis, Merck Sharp & Dohme, NeraCare, AMGEN Inc., Bristol Myers Squibb, Myriad Genetics, GSK; Financial Interests, Personal, Full or part-time Employment: Sydney Local Health District; Financial Interests, Personal, Other, Co-Medical Director fee: Melanoma Institute Australia; Financial Interests, Personal, Officer: Bridport Pathology Pty Ltd; Financial Interests, Personal and Institutional, Coordinating PI, Investigator Grant (2022/GNT2018514): National Health and Medical Research Council of Australi. J. Taube: Financial Interests, Institutional, Research Grant: Bristol Myers Squibb, Akoya Biosciences; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Merck & Co, Regeneron, AstraZeneca, Elephas, Genentech, Akoya Biosciences; Financial Interests, Personal, Stocks/Shares: Akoya Biosciences; Financial Interests, Personal, Advisory Role: Moderna. All other authors have declared no conflicts of interest.