Metastatic Colorectal Cancer
Last updated January 3, 2023
This guideline provides a review of the evidence for areas of uncertainty in the treatment of metastatic colorectal cancer (mCRC), including indications for cyotoxic chemotherapy, targeted therapies, immunotherapy, and treatment options for oligometastatic and liver-limited disease.
Doublet (folinic acid [leucovorin], fluorouracil, oxaliplatin [FOLFOX] or folinic acid [leucovorin], fluorouracil, irinotecan [FOLFIRI]) backbone chemotherapy (CT) should be offered as first-line therapy to patients with initially unresectable microsatellite stable (MSS) or proficient DNA mismatch repair (pMMR) mCRC. (EB, B, M, S)
Qualifying statement: Treatment with capecitabine plus oxaliplatin may be substituted for FOLFOX at the clinical discretion of the treating provider, and in shared decision-making with the patient.
Triplet (FOLFOXIRI) backbone CT may be offered as first-line therapy to selected patients with initially unresectable MSS or pMMR mCRC. (EB, B, M, W)
Qualifying statements for Recommendations 1.1 and 1.2:
- All patients included in the evidence-base for Recommendations 1.1 and 1.2 received anti-vascular endothelial growth factor (VEGF) antibody bevacizumab in addition to doublet or triplet CT backbone.
- Shared decision-making is recommended, including a discussion of the potential for benefit and risk of harm. While survival and recurrence outcomes are improved, grade 3 or greater adverse events are more frequent with triplet CT, compared to doublet CT.
Pembrolizumab should be offered as first-line therapy to patients with microsatellite instability-high (MSI-H) or deficient mismatch repair (dMMR) mCRC. (EB, B, M, S)
Anti-epidermal growth factor receptor (EGFR) therapy plus doublet CT should be offered as first-line therapy to patients with MSS or pMMR left-sided RAS wild-type mCRC. (EB, B, M, S)
- Anti-EGFR therapy is not recommended as first-line therapy for patients with right-sided RAS wild-type mCRC, and consistent with the qualifying statements to Recommendation 1.1 and 1.2, these patients should be offered CT and anti-VEGF therapy.
- Anti-EGFR therapy is not recommended for patients with RAS-mutant mCRC.
- Anti-EGFR therapy with triplet CT is not recommended.
- Although anti-EGFR therapy is preferred, anti-VEGF therapy remains an active treatment option for patients with left-sided, treatment-naïve RAS wild-type mCRC in the first-line setting.
- Shared decision-making is recommended, including a discussion of potential for benefit and risk of harm.
Encorafenib plus cetuximab should be offered to patients with previously treated BRAF V600E-mutant mCRC that has progressed after at least one previous line of therapy. (EB, B, M, S)
Cytoreductive surgery (CRS) plus systemic CT may be recommended for selected patients with colorectal peritoneal metastases. (EB, B, M, W)
- In the PRODIGE 7 trial, 15% of patients with isolated colorectal peritoneal metastases experienced no disease progression in the five years following surgery, indicating that CRS may be a curative option for an appropriately selected subgroup of patients.
- This recommendation applies to patients who have been deemed amenable to complete resection of colorectal peritoneal metastases, regardless of previous treatment, and who have no extraperitoneal metastases.
- Complete macroscopic cytoreduction was achieved in 91% of patients in the PRODIGE 7 trial, which is attributed to the majority of patients undergoing CRS at centers with substantial clinical experience. CRS should be considered as a treatment option only within these specialized centers.
- Multidisciplinary team (MDT) management is recommended for patients with mCRC who are considered candidates for CRS. The MDT should include expertise in medical oncology, surgical oncology, radiology, and pathology.
- Shared decision-making should include a discussion of the potential impact on quality of life and rate of adverse events associated with CRS.
Oxaliplatin-based hyperthermic intraperitoneal chemotherapy (HIPEC) is not recommended as an addition to CRS for treatment of patients with colorectal peritoneal metastases. (EB, H, M, S)
Stereotactic body radiation therapy (SBRT) may be recommended following systemic therapy for patients with oligometastases of the liver who are not considered candidates for resection. (EB, B, L, W)
Selective internal radiation therapy (SIRT) is not routinely recommended for patients with mCRC and unilobar or bilobar metastases of the liver. (EB, H, L, W)
Qualifying statement for Recommendations 6.1 and 6.2:
- MDT management is required for patients with mCRC who are considered candidates for SBRT or SIRT. The MDT should include expertise in medical oncology, radiation oncology, hepatobiliary surgery, and interventional radiology.
Surgery with or without perioperative chemotherapy should be offered to patients with mCRC who are candidates for potentially curative resection of liver metastases. (EB, B, M, W)
- Perioperative CT may be more likely to be recommended over surgery alone in patients with a greater number of metastases or with larger tumors. Shared decision-making, including discussion of the potential for benefits and risks of harm is recommended.
- The choice of perioperative CT or surgery alone, and coordination of treatment sequencing, should be discussed within a multidisciplinary team that includes expertise in medical oncology and hepatobiliary surgery.
- Perioperative CT is recommended for a total pre- and postoperative duration of 6 months, based on total duration of CT in the European Organisation for Research and Treatment of Cancer (EORTC) 40983 trial.
ASCO believes that cancer clinical trials are vital to inform medical decisions and improve cancer care and that all patients should have the opportunity to participate.
Additional information, which may include data supplements, slide sets, and other clinical tools and resources, is available at www.asco.org/gastrointestinal-cancer-guidelines.
- ASCO: American Society Of Clinical Oncology
- CRS: Cytoreductive Surgery
- CT: Chemotherapy
- EGFR: Epidermal Growth Factor Receptor
- EORTC: European Organisation For Research And Treatment Of Cancer
- FOLFIRI: Folinic Acid (leucovorin), Fluorouracil, Irinotecan
- FOLFOX: Folinic Acid (leucovorin), Fluorouracil, Oxaliplatin
- HIPEC: Hyperthermic Intraperitoneal Chemotherapy
- MDT: Multidisciplinary Team
- MSI-H: Microsatellite Instability-high
- MSS: Microsatellite Stable
- SBRT: Stereotactic Body Radiation Therapy
- SIRT: Selective Internal Radiation Therapy
- VEGF: Vascular Endothelial Growth Factor
- dMMR: Deficient Mismatch Repair
- mCRC: Metastatic Colorectal Cancer
- pMMR: Proficient DNA Mismatch Repair
Morris VK, Kennedy EB, Baxter NN, et al. Treatment of metastatic colorectal cancer: ASCO guideline. J Clin Oncol. 2022 Oct 17. doi: 10.1200/JCO.22.01690
This pocket guide is derived from recommendations in the American Society of Clinical Oncology Guideline. This resource is a practice tool based on ASCO® practice guidelines and is not intended to substitute for the independent professional judgment of the treating physician. Practice guidelines do not account for individual variation among patients. This pocket guide does not purport to suggest any particular course of medical treatment. Use of the practice guidelines and this resource are voluntary. The practice guidelines and additional information are available at www.asco.org/gastrointestinal-cancer-guidelines. Copyright © 2022 by American Society of Clinical Oncology. All rights reserved.