EP775 - Does Circulating Tumor DNA Analysis Guide Adjuvant Treatment in Colorectal Cancer? A Case Series.

Purpose/Background: Colorectal cancer (CRC) remains a significant health burden worldwide, with a notable impact on morbidity and mortality. While surgery remains the cornerstone of treatment for localized disease, adjuvant therapies play a crucial role in improving outcomes. Traditional surveillance methods primarily rely on imaging and biomarkers; however, circulating tumor DNA (ctDNA) has emerged as a promising tool for detecting minimal residual disease and guiding personalized adjuvant therapy decisions. The aim of this case series is to highlight two cases where ctDNA testing identified recurrence earlier than would have been achieved with standard surveillance and thus altered management.

Methods/Interventions: Signatera identifies patient-specific circulating cell-free tumor DNA. Sixteen tumor specific sequences are identified from the tumor sample and compared to whole normal blood. During surveillance whole blood is collected, and cell-free DNA tested with PCR and next generation sequencing to identify malignancy recurrence with a specificity of 99.5%. Guardant Reveal is a next generation sequencing (NGS)-based assay to detect genomic or epigenomic alternations in ctDNA. Unlike Signatera, it does not require a tumor sample, using plasma alone.

Results/Outcomes: Case 1: Signatera
The first patient is a 73-year-old female patient who initially presented with T1N0 rectal adenocarcinoma found on screening colonoscopy. The patient underwent transanal resection (robotic TAMIS) with final pathology upstaging to pT3N0 moderately differentiated rectal adenocarcinoma. She then was treated with adjuvant chemoradiation. This was followed by robotic LAR with diverting loop ileostomy 4 months later, with pathology showing complete response. At 3 months follow up, CEA and Signatera were negative, and flexible sigmoidoscopy showed a patent anastomosis. The ileostomy was reversed shortly thereafter. At 6 month follow up, Signatera was positive. Colonoscopy showed no masses and biopsy of anastomosis was benign, however PET-CT showed isolated lung mass, biopsy positive for metastatic adenocarcinoma status post lung resection.

Case 2: Guardant Reveal
The second patient is a 58-year-old male patient who presented with T2N0M0 upper rectal cancer on MRI. He underwent low anterior resection, but final pathology revealed T3N0. This procedure was complicated by anastomotic leak, so he was taken back for washout and diverting ileostomy. Three months later, during preparation for ileostomy reversal, Guardant reveal was positive. He underwent a flexible sigmoidoscopy which showed friable granulation tissue which was biopsied and came back positive for adenocarcinoma. Work up was completed with Pelvic MRI also showed possible recurrent tumor at the colorectal anastomosis. This prompted total neoadjuvant therapy (TNT) and eventual re-resection of recurrent rectal cancer. Postoperatively, Guardant was tested at 10-week intervals and was negative throughout observation period.

Conclusion/Discussion: In conclusion, this case series highlights two examples of ctDNA testing utilization postoperatively which identified recurrence sooner than traditional surveillance protocols in two complicated patients. The exact role in guiding surveillance and adjuvant therapy decisions for colorectal cancer patients of this data is yet to be determined. By leveraging the potential of ctDNA, we seek to improve patient outcomes and contribute to the advancement of personalized medicine in oncology.

Figure 1
Signatera Results Summary

Figure 2
Guardant Reveal Results Summary