4MO - Is it time for a new staging system for colon adenocarcinoma (CA)?

Background

Currently, the prognosis and treatment for patients (pts) with CA is primarily dictated by AJCC TNM staging criteria, which includes tumor extent (T), lymph node involvement (N), and detectable metastasis (M). However, recent studies have highlighted the prognostic and predictive value of circulating tumor (ct)DNA-based detection of molecular residual disease (MRD) post-curative-intent surgery. Here, we evaluated whether MRD status can further refine staging in pts with CA.

Methods

We retrospectively analyzed ctDNA results and clinical data from 4,291 pts with CA [N=2,314 GALAXY study; N=638, BESPOKE CRC trial; 381 from commercial ctDNA testing (real-world cohort, includes pts from MDACC’s INTERCEPT program)]. A clinically validated, personalized, tumor-informed 16-plex PCR-NGS assay (Signatera^TM) was used for ctDNA detection. MRD status was assessed at 2-10 weeks post resection, before adjuvant therapy.

Results

In the GALAXY cohort, MRD-positive pts were observed to be significantly more likely to recur compared to MRD-negative pts across all TNM stages (24-month DFS; range: 0% - 50%, Table). MRD-negative pts had a high 24-month DFS probability compared to MRD-positive pts, independent of the TNM stage (range: 56.1% - 95.9%, Table). Among MRD-positive pts, advanced TNM stages (IIIC, IV) had significantly inferior outcomes compared to earlier stages, while the TNM stage was not prognostic in the MRD-negative cohort. These results were validated in the other cohorts and will be presented. Table: 4MO

Conclusions

Our data strongly suggest that addition of post-surgical ctDNA (MRD) status to TNM staging can better risk stratify pts. Regardless of the TNM stage, the majority of patients with MRD will have recurrence at 2 years, despite selective use of adjuvant therapy. Conversely, for stage I-III patients, recurrence rates are low in the absence of detectable post-surgical MRD. While our findings are compelling, further prospective data with longer follow-up are warranted to incorporate MRD status into AJCC staging in CA.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

N.A. Dasari: Financial Interests, Personal, Advisory Board: Personalis, Illumina, Takeda, Exelixis; Financial Interests, Institutional, Funding: HutchMed, Enterome, Eisai, Taiho, Xencor, Guardant Health, Natera. A. Jurdi: Financial Interests, Institutional, Full or part-time Employment: Natera; Financial Interests, Personal, Stocks/Shares: Natera. Y. Nakamura: Financial Interests, Personal, Invited Speaker: Chugai, Merck Biopharma, Guardant Health AMEA; Financial Interests, Institutional, Funding: Taiho, Chugai, Guardant Health, Genomedia, Daiichi Sankyo, Roche Diagnostics; Financial Interests, Institutional, Invited Speaker: Seagen. V. Aushev: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc. P.M. Kasi: Financial Interests, Personal, Advisory Board, Consultancy/Advisory Board: Foundation Medicine, Natera Oncology, AstraZeneca, Merck MSD, Tempus, Bayer, Lilly, Delicath Systems, QED Therapeutics, Servier, Taiho Oncology, Exact Sciences, Eisai, Daiichi Sankyo/AstraZeneca, Seattle Genetics, SAGA Diagnostics, BostonGene, Illumina; Financial Interests, Personal, Advisory Board: Neogenomics Laboratories, Guardant Health; Financial Interests, Personal, Other, Scientific Advisory Board Member: Elicio; Financial Interests, Personal, Other, Co-Founder: Precision BioSensors Inc. M.C. Liu: Financial Interests, Personal, Full or part-time Employment: Natera, Inc.; Financial Interests, Personal, Stocks/Shares: Natera, Inc.; Financial Interests, Personal, Other, Travel Support Reimbursement: AstraZeneca, Genomic Health, Ionis; Financial Interests, Institutional, Funding: Eisai, Exact Sciences, Genentech, Genomic Health, Grail, Menarini Silicon Biosystems, Merck, Novartis, Seattle Genetics, Tesaro; Financial Interests, Institutional, Advisory Board: AstraZeneca, Celgene, Roche/Genentech, Genomic Health, GRAIL, Ionis, Merck, Pfizer, Seattle Genetics, Syndax. S. Kopetz: Financial Interests, Personal, Advisory Board: Roche, EMD Serono, Merck, Novartis, Lilly, Boehringer Ingelheim, Boston Biomedical, AstraZeneca, Bayer, Pierre Fabre, Redx Pharma, Ipsen, Daiichi Sankyo, Natera, HalioDx, Jacobio, Pfizer, Repare Therapeutics, GSK, Jazz, Xilis, AbbVie, Gilead, Mirati, Flame, Servier, Carina, Bicara, Endeavor BioMedicines, Numab Pharma, Janssen; Financial Interests, Personal, Other, Research: Inivata, Sanofi, Biocartis, Guardant Health, Array BioPharma, Genentech/Roche, EMD Serono, MedImmune, Novartis; Financial Interests, Personal, Other, Consultant: Genomic Health, Frontier Medicines, Replimune, Taiho Pharmaceutical, Cardiff Oncology, Ono Pharmaceutical, Bristol Myers Squibb-Medarex, Amgen, Tempus, Foundation Medicine, Harbinger Oncology, Takeda, CureTeq, Zentalis, Black Stone Therapeutics, NeoGenomics Laboratories, Accademia Nazionale Di Medicina; Financial Interests, Personal, Stocks/Shares: Lutris, Iylon, Navire, Xilis; Financial Interests, Personal, Ownership Interest: Frontier Medicines. T. Yoshino: Financial Interests, Personal, Invited Speaker: Chugai Pharmaceutical Co., Ltd., Merck Biopharma Co., Ltd., Bayer Yakuhin, Ltd., Ono Pharmaceutical Co., Ltd., MSD K.K., Takeda Pharmaceutical Co., Ltd.; Financial Interests, Personal, Other, Consultancy: Sumitomo Corp.; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co., Ltd., Sanofi K.K., MSD K.K., Taiho Pharmaceutical Co., Ltd., Molecular Health GmbH, Amgen K.K., Pfizer Japan Inc., Genomedia Inc., Sysmex Corp., Daiichi Sankyo Co., Ltd., Chugai Pharmaceutical Co., Ltd., Nippon Boehringer Ingelheim Co., Ltd., Eisai Co., Ltd., Roche Diagnostics K.K., Falco Biosystems Ltd., Merus N.V., Bristol Myers Squibb K.K., Medical & Biological Laboratories Co., LTD., Takeda Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.