Gastrointestinal Cancers: Biomarker-Driven Advances in CRC and NETs

Deepak Vadehra, DO Roswell Park Comprehensive Cancer Center

Key Points

• Circulating tumor DNA (ctDNA) is increasingly used to guide adjuvant therapy decisions in early-stage colorectal cancer (CRC), particularly in stage II disease, although its role in surveillance without radiographic disease remains undefined.

• In metastatic CRC, early and comprehensive biomarker testing directs first-line therapy and supports earlier use of targeted combinations.

• Across CRC and neuroendocrine tumors (NETs), individualized, biomarker-informed treatment selection and sequencing are key to optimizing outcomes.

The management of gastrointestinal (GI) cancers is advancing rapidly, with biomarker-driven decision-making and novel therapies reshaping clinical practice. At the 2026 ASCO Gastrointestinal Cancers Symposium (ASCO GI 2026), the Oncology Brothers, Rahul Gosain, MD, MBA, of Wilmot Cancer Institute, and Rohit Gosain, MD, of Roswell Park Comprehensive Cancer Center, hosted an Advancements in Oncology discussion.

Anwaar Saeed, MD, of University of Pittsburgh Medical Center, and Namrata Vijayvergia, MD, of Fox Chase Cancer Center, were among the panel who shared practical, real-world updates in CRC and NETs, with a focus on what is driving day-to-day oncology care.

ctDNA: Ready for Prime Time?

One of the biggest topics in oncology is ctDNA, and the panel examined how it is being used in clinical decision-making today. Current data show ctDNA’s increasing use to guide adjuvant treatment decisions, especially in stage II disease where chemotherapy decisions are often based on high-risk criteria without a clear consensus of when to give adjuvant therapy. 

The panelists explained that in their practice a negative (undetectable) ctDNA result may support safely omitting chemotherapy for select lower-risk patients, while a positive result strongly suggests high recurrence risk which typically leads to an adjuvant therapy recommendation.

One practical consideration is that the turnaround time for ctDNA, especially if using a tumor-informed approach, can be up to 6 weeks which can push the established temporal limits of the adjuvant treatment window.   

Despite robust prognostic data for ctDNA use, the panelists agreed that using ctDNA for broad clinical decision making is not ready for prime time. 

The limitation is particularly evident in patients who become ctDNA-positive without visible disease on imaging. In these cases, the absence of evidence-based treatment strategies can lead to patient anxiety and added financial burden, reinforcing that ctDNA surveillance remains an evolving area of research.

Emerging Clinical Trial Data in CRC

In metastatic CRC, the panelists stressed the importance of biomarker-driven treatment selection, including microsatellite instability (MSI) status; tumor sidedness; RAS mutation status; and broad molecular profiling, particularly for identifying BRAF V600E disease. For BRAF V600E–mutated metastatic CRC, the panel highlighted that combination therapy (chemotherapy plus BRAF- and EGFR-targeted agents) should be used early based on data from the BREAKWATER trial. The most recent update at ASCO GI 2026 showed that irinotecan-based therapy (FOLFIRI [folinic acid, fluorouracil, irinotecan]) plus encorafenib and cetuximab was a highly effective combination with overall similar safety data to the arm that did not receive targeted therapy. Data from BREAKWATER supports multiple chemotherapy backbone options in the first-line setting depending on patient factors and prior exposure.

The panel then shifted focus to MSI-high metastatic CRC. They raised an increasingly common clinical question: selecting between single-agent immunotherapy, immunotherapy doublets, or chemo-immunotherapy approaches.

This was particularly relevant given the presentation of the COMMIT trial at ASCO GI 2026, which compared atezolizumab monotherapy versus combination atezolizumab plus modified FOLFOX (folinic acid, fluorouracil, oxaliplatin) with bevacizumab.  Trial data demonstrated a significant progression-free survival advantage in the chemo-immunotherapy arm compared with the immunotherapy alone arm (24.5 months vs approximately 5 months). However, this raises several questions, including whether chemotherapy plus immunotherapy should be the standard, how to choose between PD-L1  and PD-1 blockade, and the broader consideration that not all immunotherapies are equally effective. 

The practical message from the panel was that immunotherapy remains the backbone, but treatment selection should be individualized based on tumor burden, the need for rapid cytoreduction, and the patient’s potential tolerance for immune-related toxicity.

Clinical Implications

Overall, the panel underscored a consistent theme across CRC and NETs: outcomes are increasingly shaped by early biomarker-informed decisions, thoughtful sequencing of therapies, and proactive side effect management that help patients remain on effective treatment longer.