Clinical Challenges in Colorectal Surgery: Management of Metastatic Colorectal Cancer

With the increasing incidence of colorectal cancer in those less than 50 years of age, one must wonder how many patients present with a Stage IV diagnosis. Take a deep dive with us discussing the management of metastatic colorectal cancer by joining our team and guests, Drs. Cathy Eng, Michael D’Angelica, and Nina Sanford.

Hosts:
- Dr. Janet Alvarez - General Surgery Resident at New York Medical College/Metropolitan Hospital Center
- Dr. Wini Zambare – General Surgery Resident at Weill Cornell Medical Center/New York Presbyterian
- Dr. Philip Bauer, Assistant Professor of Surgery, Division of Colon and Rectal Surgery, The Ohio State University Wexner Medical Center, Arthur G. James Cancer Hospital
- Dr. J. Joshua Smith MD, PhD, Chair, Department of Colon and Rectal Surgery at MD Anderson Cancer Center

Guest Speakers:
- Dr. Michael D’Angelica MD, FACS – Hepatopancreatobiliary Surgery, Memorial Sloan Kettering Cancer Center, Enid A. Haupt Chair in Surgery, Vice Chair, Education
- Dr. Cathy Eng MD, FACP - Division of Hematology and Oncology, Vanderbilt-Ingram Cancer Center, David H. Johnson Endowed Chair in Surgical and Medical Oncology, Professor of Medicine, Hematology and Oncology, VICC Associate Director for Strategic Relations and Research Partnerships, Executive Director, Young Adult Cancers Program
- Dr. Nina Sanford, MD – Radiation Oncology, UT Southwestern Medical Center, Chief of Gastrointestinal Radiation Oncology Service, Associate Professor

Learning Objectives:
1. Review the epidemiology, prognosis, and common metastatic patterns of metastatic colorectal cancer (mCRC).

2. Discuss the role of systemic chemotherapy and targeted therapies in the first- and subsequent-line treatment of mCRC, including the impact of molecular biomarkers such as MSI/MMR, RAS, BRAF, and HER2.

3. Evaluate the indications and timing of surgical and locoregional therapies for metastatic colorectal cancer, particularly in patients with liver-limited or oligometastatic disease.

4. Describe the multidisciplinary management of mCRC, including the roles of radiation therapy, systemic therapy sequencing, and palliative interventions to optimize outcomes and quality of life.

References:
Singh, M., Morris, V. K., Bandey, I. N., Hong, D. S. & Kopetz, S. Advancements in combining targeted therapy and immunotherapy for colorectal cancer. Trends Cancer 10, 598–609 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38821852/

Napolitano, S. et al. BRAFV600E mutant metastatic colorectal cancer: Current advances in personalized treatment and future perspectives. Cancer Treat. Rev. 134, (2025). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40009904/

Ciardiello, F. et al. Clinical management of metastatic colorectal cancer in the era of precision medicine. CA. Cancer J. Clin. 72, 372–401 (2022). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/35472088/

Kim, S. Y. & Kim, T. W. Current challenges in the implementation of precision oncology for the management of metastatic colorectal cancer. ESMO Open 5, e000634 (2020). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/32188714/

Biller, L. H. & Schrag, D. Diagnosis and Treatment of Metastatic Colorectal Cancer: A Review. JAMA 325, 669–685 (2021). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/33591350/

Smith, J. J. et al. Genomic stratification beyond Ras/B-Raf in colorectal liver metastasis patients treated with hepatic arterial infusion. Cancer Med. 8, 6538–6548 (2019). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/31503397/

Saadat, L. V. et al. Hepatic Artery Infusion Chemotherapy Compared to Transarterial Radioembolization For Unresectable Colorectal Liver Metastases. Ann. Surg. 10.1097/SLA.0000000000006851 doi:10.1097/SLA.0000000000006851. PubMed Link: https://pubmed.ncbi.nlm.nih.gov/?term=10.1097/SLA.0000000000006851 (Linked via DOI search as the direct PMID is still indexing)

Xiao, A. & Fakih, M. KRAS G12C Inhibitors in the Treatment of Metastatic Colorectal Cancer. Clin. Colorectal Cancer 23, 199–206 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38825433/

André, T. et al. Pembrolizumab in Microsatellite-Instability–High Advanced Colorectal Cancer. N. Engl. J. Med. 383, 2207–2218 (2020). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/33264544/

Morris, V. K. et al. Treatment of Metastatic Colorectal Cancer: ASCO Guideline. J. Clin. Oncol. 41, 678–700 (2023). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/36252154/

Xu, Z. et al. Treatments for Stage IV Colon Cancer and Overall Survival. J. Surg. Res. 242, 47–54 (2019). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/31071604/

Smith, J. J. & D’Angelica, M. I. Surgical Management of Hepatic Metastases of Colorectal Cancer. Hematol. Oncol. Clin. North Am. 29, 61–84 (2015). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/25475573/

Strickler, J. H. et al. Tucatinib plus trastuzumab for chemotherapy-refractory, HER2-positive, RAS wild-type unresectable or metastatic colorectal cancer (MOUNTAINEER): a multicentre, open-label, phase 2 study. Lancet Oncol. 24, 496–508 (2023). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/37142372/

Kruijssen, D. E. W. van der et al. Upfront resection versus no resection of the primary tumor in patients with synchronous metastatic colorectal cancer: the randomized phase III CAIRO4 study conducted by the Dutch Colorectal Cancer Group and the Danish Colorectal Cancer Group. Ann. Oncol. 35, 769–779 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38852675/

Hitchcock, K. E., Romesser, P. B. & Miller, E. D. Local Therapies in Advanced Colorectal Cancer. Hematol. Oncol. Clin. North Am. 36, 553–567 (2022). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/35562258/

Hitchcock, K. E. et al. 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 24, 201 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/38350888/

Adam, R. et al. Liver transplantation plus chemotherapy versus chemotherapy alone in patients with permanently unresectable colorectal liver metastases (TransMet): results from a multicentre, open-label, prospective, randomised controlled trial. The Lancet 404, 1107–1118 (2024). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/39306468/

Elez, E. et al. Encorafenib, Cetuximab, and mFOLFOX6 in BRAF-Mutated Colorectal Cancer. N. Engl. J. Med. 392, 2425–2437 (2025). PubMed Link: https://pubmed.ncbi.nlm.nih.gov/40444708/

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