From the Guidelines
Circulating tumor DNA (ctDNA) should be considered a valuable tool in adjuvant decision making for colon cancer patients, particularly for identifying high-risk patients who may benefit from adjuvant chemotherapy, as evidenced by recent studies 1.
Role of ctDNA in Adjuvant Decision Making
The use of ctDNA in colon cancer management is increasingly being recognized, with studies demonstrating its potential as an early marker of long-term prognosis in non-resectable disease 1.
- ctDNA testing can detect fragments of tumor DNA in the bloodstream, providing information about minimal residual disease after surgery.
- For stage II colon cancer patients, ctDNA positivity after surgery may identify high-risk patients who would benefit from adjuvant chemotherapy despite otherwise favorable clinical features.
- Conversely, ctDNA negativity might spare some patients from unnecessary chemotherapy.
Current Guidelines and Recommendations
According to the ESMO clinical practice guidelines for diagnosis, treatment, and follow-up of localized colon cancer 1,
- Adjuvant therapy options should be fully discussed with the patient, taking into consideration tumor risk of recurrence, expected benefit from chemotherapy, and risk of complications.
- The risk of relapse after a colon cancer resection should be assessed by integrating the TNM staging, MMR/MSI status, and number of lymph nodes sampled.
- However, the guidelines do not currently recommend the use of gene expression signatures or ctDNA in routine practice due to lack of predictive value for chemotherapy benefit 1.
Emerging Evidence and Future Directions
Recent studies have demonstrated the potential of ctDNA in predicting disease recurrence and guiding adjuvant therapy decisions 1.
- A study involving 123 patients with locally advanced rectal cancer showed that total ctDNA at diagnosis was of modest prognostic value, with patients having ctDNA levels above the 75th percentile having a higher risk of disease recurrence 1.
- Another study of 159 patients with locally advanced rectal cancer showed that the presence of postoperative ctDNA was predictive of disease recurrence, irrespective of the use of adjuvant chemotherapy 1. Therefore, based on the most recent and highest quality evidence 1, ctDNA should be considered a valuable tool in adjuvant decision making for colon cancer patients, particularly for identifying high-risk patients who may benefit from adjuvant chemotherapy.
From the Research
Role of ctDNA in Adjuvant Decision Making
- ctDNA analysis can detect minimal residual disease and predict recurrence in patients with stage II colon cancer, helping inform adjuvant treatment decisions 2
- The presence of ctDNA after completion of chemotherapy is associated with an inferior recurrence-free survival, indicating its potential role in guiding adjuvant therapy 2, 3
- ctDNA detection after stage II colon cancer resection provides direct evidence of residual disease and identifies patients at very high risk of recurrence 2
Prognostic Value of ctDNA
- ctDNA is a strong predictor for recurrence and survival after surgery and adjuvant chemotherapy in early stage colon cancer 4
- Serial measurement of ctDNA shows great promise as a marker for both prognosis and response to treatment in early colon cancer 4
- ctDNA analysis after surgery is a promising prognostic marker in stage III colon cancer, and postchemotherapy ctDNA analysis may define a patient subset that remains at high risk of recurrence despite completing standard adjuvant treatment 3
ctDNA-Guided Adjuvant Therapy
- ctDNA-guided adjuvant immunotherapy may be beneficial in colorectal cancer, particularly in patients with dMMR/MSI-H stage III CRC who do not respond to oxaliplatin-based chemotherapy 5
- Using ctDNA instead of historical clinicopathological factors to select patients for adjuvant chemotherapy may reduce inappropriate therapy 6
- ctDNA is an independent prognostic factor, and its use in the adjuvant setting may improve treatment outcomes for colon cancer patients 6