This Week in CRC Research

TRIAL DATA

Perioperative Pembrolizumab Shows High Complete Response Rate in MSI-H/dMMR Localized Colorectal Cancer — Journal of Clinical Oncology

Journal of Clinical Oncology. MSI-H/dMMR tumors have defects in DNA repair machinery that make them highly responsive to immunotherapy.

What this means

If you have MSI-H or dMMR colorectal cancer that hasn't spread beyond the colon, immunotherapy before surgery may become a new treatment option. Ask your care team whether your tumor has been tested for MSI-H/dMMR status and if perioperative immunotherapy trials are available.

SCREENING

Circulating Tumor DNA Before Surgery Predicts Recurrence After Liver Metastasis Resection — Clinical Cancer Research

Researchers analyzed blood samples from 116 patients with metastatic colorectal cancer confined to the liver who underwent surgery after chemotherapy. They measured circulating tumor DNA (ctDNA)—fragments of cancer DNA in the bloodstream—both before and after surgery. Patients with detectable ctDNA before surgery had significantly worse outcomes, even if ctDNA cleared after the operation. This suggests pre-surgery ctDNA status provides important prognostic information beyond post-surgery testing alone.

What this means

If you're being considered for liver surgery after chemotherapy, ctDNA testing before the operation may help your care team assess your risk of recurrence and plan follow-up monitoring. This blood test could eventually guide decisions about additional treatment after surgery.

TRIAL DATA

STRATEGIC-1 Trial Defines Optimal Treatment Sequence for RAS/BRAF Wild-Type Metastatic Colorectal Cancer — Signal Transduction and Targeted Therapy

The Phase III STRATEGIC-1 trial (NCT01910610) compared different sequences of chemotherapy combined with either anti-EGFR antibodies (cetuximab/panitumumab) or anti-angiogenic drugs (bevacizumab) in patients with RAS and BRAF wild-type metastatic colorectal cancer. The study aimed to determine the best order to use these treatments to maximize patient survival. RAS/BRAF wild-type tumors lack certain mutations and can respond to anti-EGFR therapy.

What this means

If your tumor is RAS and BRAF wild-type, this trial provides evidence about which targeted therapy to use first and how to sequence treatments over time. Ask your oncologist about your tumor's mutation status and how these findings apply to your treatment plan.

TREATMENT

HER2 Amplification May Predict Resistance to Anti-EGFR Therapy in Metastatic Colorectal Cancer — ESMO Gastrointestinal Oncology

An exploratory analysis from the CAPRI-2 GOIM trial examined HER2 gene alterations in patients with RAS/BRAF wild-type, microsatellite stable metastatic colorectal cancer treated with FOLFIRI chemotherapy plus cetuximab (an anti-EGFR antibody). Researchers found that HER2 amplification or mutation may be associated with poorer response to anti-EGFR therapy, suggesting HER2 testing could help identify patients unlikely to benefit from this treatment approach.

What this means

If you're considering anti-EGFR therapy like cetuximab or panitumumab, ask whether your tumor has been tested for HER2 alterations. If HER2 is amplified or mutated, you may benefit from HER2-targeted therapies instead, which are increasingly available in clinical trials.

LIVING WITH CRC

Circulating Tumor DNA Testing May Increase Fear of Recurrence in Some Colorectal Cancer Survivors — Psycho-Oncology

Researchers interviewed colorectal cancer survivors enrolled in the DYNAMIC trials, which used ctDNA testing to guide decisions about adjuvant chemotherapy after surgery. While many patients valued the precision of ctDNA testing, some experienced heightened fear of cancer recurrence, particularly when waiting for test results or receiving positive ctDNA findings. The study highlights the need for psychological support alongside ctDNA-guided care.

What this means

If you're undergoing ctDNA surveillance after treatment, it's normal to feel anxious about test results. Talk to your care team about your concerns—many cancer centers offer counseling and support groups to help manage fear of recurrence. The emotional impact of testing is just as important as the medical information it provides.

🔬 Under 50 Spotlight

Research relevant to early-onset and younger CRC patients

Early-Onset CRC Liver Metastases Show Distinct Molecular Features — A review in International Journal of Molecular Sciences synthesized evidence showing that liver metastases from early-onset colorectal cancer (diagnosed before age 50) have distinct genomic and immunologic characteristics compared to those from older adults. These differences may explain the more aggressive behavior often seen in younger patients and could inform development of age-specific treatment strategies.

Education Level Linked to Young-Onset CRC Mortality Disparities — Analysis published in JAMA Oncology found significant disparities in young-onset colorectal cancer mortality based on education level, suggesting socioeconomic factors play a critical role in outcomes for younger patients. This highlights the need for targeted interventions to improve access to screening and treatment in underserved populations.

Dietary Sugar Intake Linked to Early-Onset CRC Risk in New Zealand — A study in the New Zealand Medical Journal examined the role of dietary sugar in rising early-onset colorectal cancer rates, particularly among Māori populations. Researchers found evidence suggesting that excessive sugar consumption and associated metabolic dysregulation may contribute to colorectal cancer development in younger adults, emphasizing the importance of dietary interventions.

🧬 Biomarker Spotlight

Research by genetic subtype — KRAS, BRAF, MSI-H, HER2, and more

Mucinous Histology May Reduce Immunotherapy Response in MSI-H Metastatic CRC — A multinational study found that patients with MSI-H/dMMR metastatic colorectal cancer who have mucinous histology (≥50% mucinous component) may have reduced response to immune checkpoint inhibitors compared to non-mucinous MSI-H tumors. The mucinous phenotype has been associated with an immune-cold microenvironment, potentially explaining this resistance pattern.

TGFβ Signaling Drives Metastasis in KRAS-Mutant Colorectal Cancer — Research published in Cancer Letters identified interferon regulatory factor 2 (IRF2) as a metastasis suppressor that is directly repressed by TGFβ-SMAD2/3 signaling in KRAS-mutant colorectal cancer. This finding reveals a new mechanism by which TGFβ promotes the aggressive metastatic behavior characteristic of KRAS-mutant tumors.

BRAF-Mutated Colon Cancer Shows Higher Risk of Central Lymph Node Metastases — A prospective study in the Journal of Clinical Medicine found that BRAF-mutated stage I-III colon cancer has increased risk of central mesocolic lymph node metastases compared to BRAF wild-type tumors. This molecular profiling could help identify patients who may benefit from extended lymphadenectomy during surgery.

Pembrolizumab Achieves Complete Response in Pediatric Lynch Syndrome CRC — A case report in Drugs in Context described a 12-year-old boy with Lynch syndrome-associated colorectal cancer who developed severe cardiac toxicity after initial chemotherapy. Treatment was switched to off-label pembrolizumab, resulting in a complete response. This highlights the potential of immunotherapy in pediatric Lynch syndrome-associated colorectal cancer, though more data are needed.

Clinical Trials Update

Long-Term Results: Adjuvant Chemotherapy After Liver Metastasis Surgery (JCOG0603) — Journal of Clinical Oncology

Journal of Clinical Oncology.

AZUR-4: Neoadjuvant Dostarlimab Plus Chemotherapy in MSS Colon Cancer — Clinical Colorectal Cancer

The AZUR-4 trial protocol has been published in Clinical Colorectal Cancer.

Phase II: Pembrolizumab Plus Capecitabine and Bevacizumab in MSS Metastatic CRC — Clinical Colorectal Cancer

Clinical Colorectal Cancer.

FIERCE Study: Trifluridine/Tipiracil With Radiation in Rectal Cancer — Clinical Colorectal Cancer

Results from the FIERCE study have been published in Clinical Colorectal Cancer.

By the Numbers

116 patients

Number of metastatic colorectal cancer patients with liver-limited disease analyzed in the circulating tumor DNA study published in Clinical Cancer Research this week. The research showed that ctDNA status before surgery—not just after—provides critical prognostic information about recurrence risk. This finding could change how doctors use blood-based monitoring to guide treatment decisions for patients undergoing liver metastasis resection.

Resources

Understanding Biomarker Testing

The Colorectal Cancer Alliance offers a comprehensive guide to biomarker testing in colorectal cancer, explaining MSI-H/dMMR, RAS, BRAF, HER2, and other important mutations that guide treatment decisions.

Visit the Colorectal Cancer Alliance Biomarker Testing Guide →

Ask Your Care Team

Based on this week's research, here are specific questions to bring to your oncologist:

  • If your tumor is MSI-H or dMMR: "Am I eligible for perioperative immunotherapy trials like IMHOTEP? Could pembrolizumab before surgery help shrink my tumor?"
  • If you're considering liver metastasis surgery: "Should I have ctDNA testing before my surgery to help predict my risk of recurrence? How would that change my treatment plan?"
  • If your tumor is RAS/BRAF wild-type: "Has my tumor been tested for HER2 alterations? If I have HER2 amplification, should I consider HER2-targeted therapy instead of anti-EGFR treatment?"