ESMO Consensus Guidelines for Metastatic Colorectal Cancer Offer Widely Expanded Recommendations

Walter Alexander

October 2016, Vol 6, No 10 - Guidelines Update


The release of the updated European Society for Medical Oncology (ESMO) consensus guidelines for the management of patients with metastatic colorectal cancer (CRC) was prompted by significant new clinical trial evidence and an advancing understanding of the role and impact of molecular selection in CRC (Van Cutsem E, et al. Ann Oncol. 2016;27:1386-1422), said co-author of the guidelines Eric Van Cutsem, MD, PhD, University Hospitals Gasthuisberg/Leuven, Belgium, at the 2016 ESMO World Congress on Gastrointestinal Cancer, in Barcelona, Spain.

Dr Van Cutsem co-chaired the meeting, where he spoke about the guidelines in an oral presentation. “Management of metastatic colorectal cancer is becoming more complex. It requires a strategic approach and evidence-based patient selection for the best treatment options,” Dr Van Cutsem said.

What largely distinguishes the 2016 ESMO guidelines on the management of metastatic CRC from the 2014 ESMO guidelines is the expanded details of the recommendations. The guideline authors note that although the past decade has seen enhanced outcomes for patients with metastatic CRC, it remains unclear which advances and strategic changes in treatment and management have been responsible for the improvements in metastatic CRC outcomes. Potential factors include:

  1. Changes in patient clinical presentation because of earlier detection of metastatic disease or closer follow-up after primary tumor resection
  2. Improvements in the efficacy and administration of systemic therapies
  3. Increases in treatments aimed at facilitating resection of metastases for cure or durable relapse-free survival, including the increased use of other ablative techniques
  4. “Continuum-of-care” strategies coupled with the early integration of optimal supportive care.

Expanding Previous Recommendations

The 2014 ESMO guidelines for CRC were a 9-page document. To address the growing complexity and subtlety of relevant knowledge, the 2016 guidelines have expanded to 37 pages comprising 21 recommendations.

The first 8 recommendations range across tissue handling, tissue selection, and biomarker testing. For example, testing to determine RAS mutation status is recommended for all patients ­at the time of diagnosis, and should include at least KRAS exons 2, 3, and 4 (codons 12, 13, 59, 61, 117, and 146), and NRAS exons 2, 3, and 4 (codons 12, 13, 59, 61, and 117).

In addition, BRAF mutation testing for prognostic assessment (and/or potential selection for clinical trials) is strongly recommended, along with microsatellite instability testing, which can assist clinicians in genetic counseling, and offers a strong predictive value for the use of immune checkpoint inhibitors in metastatic CRC.

In an interview, Dr Van Cutsem underscored that although microsatellite instability testing is an emerging biomarker, it is not yet mandatory for the management of metastatic CRC. Similarly, testing for other biomarkers, such as EGFR or HER2, is emerging but is not yet recommended as a routine practice for patient management.

Recommendation 9 covers emerging technologies (eg, circulating tumor cell number; liquid circulating tumor DNA biopsies; whole genome, whole exome, and whole transcriptome analysis) that are reserved for research settings.

Recommendation 10 discusses specific treatment strategies for patients with oligometastatic disease, followed by recommendations on perioperative treatment and conversion therapy for patients with potentially resectable disease.

Recommendations 14 and 15 introduce ablative techniques, which are gaining “increasing importance” in the management of metastatic CRC, including the local use of ablative therapy, such as thermal ablation, high conformal radiation, and radio­frequency ablation.

Recommendation 16 discusses the use of embolization. This recommendation was expanded from the 2014 ESMO guidelines to include chemoembolization, which may be considered for patients with liver-limited disease that does not respond to available chemotherapeutic options. In addition, the 2016 guidelines recommend radioembolization with yttrium-90 microspheres for liver-limited disease; this recommendation has not changed since the 2014 ESMO guidelines.

Recommendation 17 underlines that complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be considered for patients with limited peritoneal metastases in centers that are very experienced in the use of HIPEC.

Determining a Therapeutic Strategy

The remaining recommendations 18 through 21 encompass first-line therapy according to targeted agent used, maintenance therapy, second-line therapy, and third-line therapy.

Discussing innovations in pharmacotherapy for third-line therapy in metastatic CRC, Dr Van Cutsem said that trifluridine plus tipiracil (Lonsurf) is recommended for the treatment of patients with metastatic CRC who had received fluoropyrimidine-, oxaliplatin-, and irinotecan- based chemotherapy; an anti–VEGF (vascular endothelial growth factor) biologic drug; and, if RAS wild-type, an anti–EGFR (epidermal growth factor receptor) monoclonal antibody. The combination of tri­fluridine plus tipiracil was approved by the FDA in September 2015.

“These recommendations should help us to fine-tune and improve our strategies, and guide treatment options in order to improve outcomes,” Dr Van Cutsem concluded.