The role of Liquid Biopsy in resected Stage II and III colon Cancer

Introduction: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer in the world with 2 million new cases every year and its incidence has been steadily rising . Early stage at diagnosis, surgical resection and adjuvant chemotherapy using Oxaliplatin and 5FU, represent the curative treatment for stage II (high risk) and III. Research is moving towards the identification of personalized biomarkers (diagnostic and prognostic) with high specificity and sensitivity for these patients . “Liquid Biopsy (LB)“could represent the new era for biomarkers detection. Aims: Our objetive consists in identifying the variations of the molecular profiles detected in the ctDNA before and after surgery in stage II/III CRC pts and to evaluate the percentage of LB positivity, false negative and false positive in our series. Materials and methods: The molecular profile of the tumor will first be assessed on the tumor specimen by using a custom NGS panel . Once the driver mutations on the tumor specimen has been evaluated, they will be searched for analyzing the ctDNA by DDPCR.In particular, the mutations found in the tumor speciimen should also be found in the ctDNA extracted from the sample taken before surgery, while they should be absent in the postoperative sample before the start of adjuvant therapy and in follow up visit. Results: From November 2020 to February 2022 of the 42 patients enrolled, only 33 were able to carry out all the steps of the study.Despite the analytical sensitivity of ctDNA assay we register 25% of false negatives (1/4 progressed disease) and 50% of probably false positives (3 LB+ of 6 LB+ at P3). The sites of disease progression were: 3/4 lymphnodes, 1/4 brain 2/4 lung. The median lead time was 7 weeks. The mutations found in the specimen and in the LB are in line with those described in the literature. The most critical issue was the small simple size due to slow accrual of patients due to the Covid19 pandemia that reduced outpatient visit , poor patient cooperation for cultural reasons, not motivated to contribute to research, withdraw of informed consent, patients’s choice to receive treatments in another hospital Conclusion: Our stydy showed that ct DNA could be a prognostic biomarker infact in our series patients with ctDNA-Positive were high risk of recurrence while those with ctDNA-Negative were at low risk of recurrence. Although liquid biopsy research requires dedicated operators,important patient cooperation we showed that this tecnique can be used in clinical practice in the near future although we don’t know if the costs can translate into an increase in survival benefit for these patients. Care about the patient journey: the emotional impact of an positive liquid biopsy result, without radiological and/or clinical relapse should be considered. Psychological support should be provided for these patients.