Prognostic value of post-surgery liquid biopsy cell-free circulating tumor DNA in stage III colon cancer patients - PLCRC-PROVENC3 study

Abstract Introduction: Stage III colon cancer patients are offered surgery followed by adjuvant chemotherapy (ACT) according to Dutch clinical guidelines. However, only 15-20% of the patients benefit from ACT: 50% would be cured by surgery alone and are thus being overtreated, while 30-35% will experience a recurrence despite adjuvant treatment. Therefore, there is a need for prognostic biomarkers to better stratify this group of patients for ACT. Recent studies in non metastatic colorectal cancer have shown that detection of cell-free circulating tumor DNA (ctDNA) in blood after surgery indicates presence of minimal residual disease, and is highly prognostic for relapse. Hence, ctDNA based liquid biopsies could be a promising approach to guide post-surgery treatment decisions in stage III colon cancer. Aim: Determine the prognostic value of post-surgery ctDNA in stage III colon cancer patients treated with ACT in order to reduce futile treatment. Study design and Methods: The Prospective Dutch Colorectal Cancer Cohort study PLCRC (www.PLCRC.nl) offers a nationwide infrastructure to accrue colorectal cancer patients in nearly all (>60) hospitals in the Netherlands. Patients give informed consent for collection of clinical data, tissue and blood samples. “PROVENC3” (PROgnostic Value of Early Notification by Ctdna in Colon Cancer stage 3) is a prospective observational subcohort of PLCRC consisting of 267 stage III colon cancer patients treated with ACT,open for patient accrual in 25 hospitals. Blood samples are collected pre-surgery, post-surgery, post-ACT and longitudinally every six months up to 3 years. We will apply tumor-informed detection of ctDNA mutations by integrated analysis of targeted sequencing of a panel of 30 genes in cfDNA (PGDx elio plasma resolveassay) with a panel of 500 genes in DNA from formalin-fixed paraffin-embedded tumor tissue (PGDx elio tissue complete assay). The clinical, pathological, and molecular data will be integrated in cBioPortal. Results and future directions: 267 patients have been included. Approximately 950 blood samples have been collected to date. Once sequencing data is obtained, multivariate Cox regression analysis will be used to assess the association between post-surgery ctDNA detection and progression-free and overall survival. Ultimately, the results of this study will be used to design an ethically acceptable and cost-effective ctDNA-guided interventional trial in stage III colon cancer patients, in order to improve the risk stratification and reduce futile ACT and its associated side-effects. Citation Format: Carmen Rubio Alarcon, Dave E. van der Kruijssen, Suzanna J. Schraa, Sietske C. Nassau, Leticia G. León, Lana Meiqari, Linda J. Bosch, John K. Simmons, Mark Sausen, Amy Greer, Samuel V. Angiuoli, Jeanine M. Roodhart, Victor E. Velculescu, Daan van den Broek, Cornelis J. Punt, Veerle M. Coupé, Miriam Koopman, Gerrit A. Meijer, Geraldine R. Vink, Remond J. Fijneman. Prognostic value of post-surgery liquid biopsy cell-free circulating tumor DNA in stage III colon cancer patients - PLCRC-PROVENC3 study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 536.