Prevention of recurrent disease by additional chemotherapy in patients with detectable circulating tumor DNA in the blood after surgery for stage II (lymph nodes unaffected) colon cancer.

Background and rationale

Patients with stage II CC have a good chance of survival, however, 15-20% of patients with stage II CC experience recurrence of disease. Only patients with clinicopathological high-risk factors (T4 tumor as most important factor) are offered ACT.

In stage II CC solid support and consensus is lacking regarding effectiveness of ACT.

Recently, ctDNA was shown to have a strong association with disease recurrence in stage II CC. In >80% of patients with detectable ctDNA after surgery disease recurrence occurred within 2 years. Whether ACT can reduce the RR in patients with detectable ctDNA is not known, and therefore we propose a cohort multiple Randomized Controlled Trial (cmRCT) to evaluate effectiveness of ACT in stage II CC patients with detectable ctDNA after surgery.

Methods
Stage II CC patients, included in the Prospective Dutch CRC cohort (PLCRC) and not considered for ACT by the treating physician, will be randomized 1:1 according to the cmRCT design. In patients randomized to the intervention arm, ctDNA results will be determined immediately after surgery. Patients with detectable ctDNA will be offered ACT (CAPOX/FOLFOX). In the control group, ctDNA will be analyzed batch-wise at the end of the trial and results will not be used in patient care. Patients in this arm will not receive ACT according to standard clinical care.

Adjuvant chemotherapy in stage II CC patients with detectable postoperative ctDNA will lead to a 30% lower risk of disease recurrence within two years compared to standard treatment (regular follow-up).

- Enrollment in PLCRC and observational PLCRC-MEDOCC study before surgery

Obtaining IC, blood withdrawal 1-3 weeks after surgery, ctDNA analysis

Adjuvant chemotherapy 6 months CAPOX or FOLFOX