ctDNA-Based Adjuvant Chemotherapy for High-Risk Rectal Cancer

The goal of this clinical trial is to investigate whether adjuvant chemotherapy can prevent disease recurrence in patients with high-risk rectal cancer who have detectable ctDNA after surgery. The main research question the REACT study aims to answer is: \- Does adjuvant chemotherapy improve disease-free survival in patients with high-risk rectal cancer with detectable ctDNA after surgery? Interventions: \- Patients with detectable ctDNA after surgery and randomised to the experimental group will be offered adjuvant chemotherapy (4 cycles CAPOX/6 cycles FOLFOX) within 12 weeks after surgery.

Inclusion Criteria * Detectable ctDNA in the postoperative blood sample * Age ≥ 18 years * WHO performance score 0-1 * Informed consent for PLCRC with specific consent for additional blood withdrawals and offering of future experimental research * Informed consent for the REACT trial. * Histological confirmed rectal cancer; either treated with neoadjuvant (chemo)radiotherapy, and/or clinical/pathological T3/T4 and/or N+ in case no neoadjuvant therapy was administered. * Eligible to receive treatment with combination adjuvant chemotherapy (CAPOX/FOLFOX) according to the treating physician. * Mentally competent and able to read and understand Dutch language. Exclusion Criteria: * Metastatic disease * Another malignancy in previous 5 years, with the exception of treated carcinoma in situ or skin cancer other than melanoma * Incomplete primary tumour resection (R1 or R2 resection) * Contra-indication for fluoropyrimidines or oxaliplatin * Neoadjuvant oxaliplatin based systemic treatment, e.g. treated with the RAPIDO regimen consisting of short course radiotherapy followed by 6 cycles of CAPOX or 9 cycles of FOLFOX prior to surgery * Patients with a clinical complete response, who will not undergo surgery. * Pregnant and lactating women * History of psychiatric disability judged by the investigator to be clinically significant, precluding informed consent or interfering with compliance of the intervention group * Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator * Serious infections (uncontrolled or requiring treatment) * Current or recent (within 28 days prior to randomisation) treatment with another investigational drug or participation in another study interfering with the primary endpoint.