What are the next steps for a patient with T4 colon cancer, status post resection and adjuvant therapy, now presenting with elevated circulating tumor (ct) DNA?

From the Guidelines

For a patient with T4 colon cancer who has undergone resection and adjuvant therapy but now has elevated circulating tumor DNA (ctDNA), I recommend immediate referral to a medical oncologist for comprehensive evaluation and management, as the most recent and highest quality study suggests that patients at high risk of recurrence, such as those with T4 tumors, should receive adjuvant chemotherapy for a duration of 6 months 1. The detection of elevated ctDNA after treatment suggests possible molecular residual disease or early recurrence. The oncologist will likely order additional imaging studies such as CT scans of the chest, abdomen, and pelvis, and possibly a PET scan to identify any sites of recurrence. If metastatic disease is confirmed, treatment typically involves systemic therapy with combination chemotherapy regimens such as FOLFOX (5-fluorouracil, leucovorin, and oxaliplatin) or FOLFIRI (5-fluorouracil, leucovorin, and irinotecan), potentially combined with targeted agents like bevacizumab or cetuximab depending on molecular testing results, as suggested by previous studies 1. Some key points to consider in the management of such patients include:

• The importance of regular monitoring with repeat ctDNA testing every 3-6 months along with standard surveillance for early detection of clinical recurrence.
• The potential benefits of enrollment in a clinical trial specifically addressing molecular residual disease if no visible disease is detected but ctDNA remains elevated.
• The consideration of early intervention with chemotherapy even without radiographically visible disease, as some oncologists may recommend.
• The use of additional imaging methods such as MRI, PET scan, or contrast-enhanced ultrasound if an anatomical resection can be performed, as suggested by previous guidelines 1. Overall, the management of patients with T4 colon cancer and elevated ctDNA after resection and adjuvant therapy requires a comprehensive and multidisciplinary approach, taking into account the latest evidence and guidelines 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Management of T4 Colon Cancer with Elevated Circulating DNA

• The management of T4 colon cancer with elevated circulating DNA involves several considerations, including the use of adjuvant chemotherapy and the role of circulating tumor DNA (ctDNA) in guiding treatment decisions 2.
• Adjuvant chemotherapy has been shown to improve disease-free survival and overall survival in patients with T4 colon cancer, particularly those with lymphovascular invasion (LVI) 3.
• The use of ctDNA to guide treatment decisions is an area of ongoing research, with studies suggesting that it may have prognostic value and potentially personalize treatment after radical surgery 2.
• Neoadjuvant strategies for T4 colon cancer are also being explored, with conventional XELOX and FOLFOX chemotherapy being the most commonly administered interventions 4.
• The benefit of adjuvant chemotherapy in patients with T4 UICC II colon cancer has been demonstrated, with studies showing a significant survival benefit in respect of overall survival and recurrence-free survival 5.

Adjuvant Chemotherapy

• Adjuvant chemotherapy is considered the standard of care in patients with UICC stage III colon cancer after R0 resection, and its benefit in patients with T4 UICC II colon cancer is being explored 6, 5.
• The choice of adjuvant chemotherapy regimen, including the use of oxaliplatin, is an important consideration, with studies suggesting that oxaliplatin added to fluorouracil/capecitabine may be superior to fluropyrimidine alone 6.
• The duration of adjuvant chemotherapy is also an important consideration, with studies such as the International Duration Evaluation of Adjuvant Chemotherapy (IDEA) trial exploring the optimal duration of treatment 6.

Circulating Tumor DNA

• Circulating tumor DNA (ctDNA) has been shown to have clinically relevant results in early-stage colon cancer patient management, with its prognostic value being stronger than that of available clinico-pathological biomarkers 2.
• The use of ctDNA to guide treatment decisions is an area of ongoing research, with studies exploring its potential to personalize treatment after radical surgery 2.
• Two main avenues of ctDNA testing are being pursued: tumor-informed vs tumor-agnostic assays, with two main clinical trial designs being explored: ctDNA-based strategy and ctDNA-by-treatment interaction 2.