The ERASur Trial Surpasses One-Third Accrual: A Nationwide Effort to Define the Role of Total Ablative Therapy in Limited Metastatic Colorectal Cancer

The ERASur trial (Alliance A022101/NCT05673148) has reached a significant enrollment milestone, surpassing one-third of its total patient accrual. This achievement signals robust nationwide engagement in a study poised to answer a fundamental clinical question: Should patients with limited metastatic colorectal cancer receive aggressive local treatment of all metastatic sites in addition to chemotherapy? [1]

Colorectal cancer remains the second leading cause of cancer-related death in the United States, with about 160,000 new cases diagnosed annually. While advances in systemic therapy and screening have lowered incidence and mortality rates, a troubling rise in aggressive disease among younger adults adds urgency to trials seeking better outcomes.

About one-third of diagnosed patients with colorectal cancer (CRC) will ultimately develop metastatic disease. While a small percentage of patients can be considered for curative resection, more patients have limited disease that can be considered for local therapy. For patients with metastases limited to the liver, local interventions such as surgery or ablative radiation have demonstrated survival benefits. However, for patients with metastatic spread to multiple organs (up to four sites), there is no definitive evidence to guide the use of aggressive local therapies beyond the liver. The ERASur trial addresses this critical evidence gap.[2]

Trial Design and Objectives
ERASur (Evaluation of Resection or Ablation for Limited Metastatic Colorectal Cancer) is a pragmatic, randomized phase 3 trial (Alliance A022101/NRG-GI009) sponsored by the National Cancer Institute (NCI) and conducted by the Alliance for Clinical Trials in Oncology. The trial is enrolling adults whose metastatic colorectal cancer is limited to four or fewer sites, as confirmed by imaging after four to twelve months of first-line chemotherapy. The study employs a pragmatic interventional design to test the efficacy and safety of adding multimodality total ablative therapy (TAT), which includes surgical resection, microwave ablation, and/or stereotactic ablative body radiotherapy (SABR), with SABR required for at least one lesion, to standard-of-care systemic therapy in patients with limited mCRC.[1]

Participants are randomized to one of two arms:

• Arm 1: Total ablative therapy (surgery, radiation, or thermal ablation) targeting all known metastatic sites, followed by standard systemic therapy.
• Arm 2: Standard systemic therapy alone.

The primary outcome is overall survival, with secondary endpoints including progression-free survival and safety.

Nationwide Engagement and Multidisciplinary Collaboration
More than 183 sites across the United States, including many community cancer centers, are participating in ERASur. The trial’s broad reach reflects the commitment of clinicians, research teams, and patients to advancing evidence-based care. Cancer centers with the highest enrollment include The Ohio State University Comprehensive Cancer Center, Memorial Sloan Kettering Cancer Center, University of Nebraska Medical Center, and UF Health Cancer Center.

Eric Miller, MD, PhD, a radiation oncologist at The Ohio State University Comprehensive Cancer Center and principal investigator of ERASur, emphasized the significance of this accrual milestone:

“This milestone reflects the commitment of patients, clinicians, and research teams across the country to answer a question that has major implications for how we treat metastatic colorectal cancer. If successful, ERASur could help redefine the role of aggressive local therapy beyond liver-only metastases,” he said.

Implications for Clinical Practice
The growing momentum behind ERASur was recently showcased at the Society of Surgical Oncology (SSO) 2026 Annual Meeting in Phoenix, Arizona. The trial’s multidisciplinary design and potential to shape future standards of care drew significant attention from the oncology community.[3]

Colorectal cancer patients have experienced notable improvements in survival following local treatment of isolated metastases, particularly in the liver. However, the safety and efficacy of ablative therapies—such as microwave ablation and stereotactic body radiation therapy—for patients with multiple metastatic sites remain unclear. ERASur is uniquely positioned to provide definitive evidence regarding the benefit of adding total ablative therapy to standard systemic treatment in this patient population.

The trial is set to enroll more than 150 patients, with recruitment ongoing. Each patient enrolled brings the field closer to answering whether a more aggressive local approach can meaningfully extend survival for those with limited metastatic colorectal cancer.

What’s next
Reaching one-third patient accrual is a major milestone for the ERASur trial and a testament to the dedication of participating centers and patients nationwide. The study’s results are anticipated to inform and potentially redefine standards of care for patients with limited metastatic colorectal cancer, offering hope for improved outcomes in this challenging disease setting.

Clinical trials
Testing the Addition of Total Ablative Therapy to Usual Systemic Therapy Treatment for Limited Metastatic Colorectal Cancer, The ERASur Study
ClinicalTrials.gov ID NCT05673148

Reference
[1] Hitchcock KE, Miller ED, Shi Q, Dixon JG, Gholami S, White SB, Wu C, Goulet CC, George M, Jee KW, Wright CL, Yaeger R, Shergill A, Hong TS, George TJ, O’Reilly EM, Meyerhardt JA, Romesser PB. Alliance for clinical trials in Oncology (Alliance) trial A022101/NRG-GI009: a pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer: evaluating radiation, ablation, and surgery (ERASur). BMC Cancer. 2024 Feb 13;24(1):201. doi: 10.1186/s12885-024-11899-2. PMID: 38350888; PMCID: PMC10863118.
[2] Miller ED, Hitchcock KE, Romesser PB. Oligometastatic Colorectal Cancer: A Review of Definitions and Patient Selection for Local Therapies. J Gastrointest Cancer. 2023 Dec;54(4):1116-1127. doi: 10.1007/s12029-022-00900-5. Epub 2023 Jan 18. PMID: 36652155; PMCID: PMC10352468.
[3] Gholami S, Romesser P, Shi Q, Dixon J, White S, Wu C, Goulet C, Jee KW, Wright C, Yaeger R, Shergill A, Hong T, George T, O’Reilly EM, Meyerhardt J, Hitchcock K, Miller ED. EP182. Alliance A022101/NRG-GI009: A pragmatic randomized phase III trial evaluating total ablative therapy for patients with limited metastatic colorectal cancer – evaluating radiation, ablation, and surgery (ERASur). Poster presented during the Society of Surgical Oncology (SSO) 2026 Annual Meeting in Phoenix, Arizona.

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