Table 3.

Summary of recommendations

The European Society of Medical Oncology (ESMO) proposes assigning patients to one of 4 groups to guide first-line therapeutic strategies (V, C)

The expanded RAS mutation analysis needs to be known before anti-EGFR treatment in mCRC, performed on tumor DNA from any location, as long as the performing lab complies with nationally or internationally qualified quality assurance programs (I, A)

Plasma can be a surrogate source tissue for mutational analysis when no tumor sample is available or for testing secondary resistance (III, C)

Patients with asymptomatic primary tumor and unresectable disease should start initial palliative chemotherapy. Resection of the primary tumor should only be performed in patients who develop serious complications (II, B)

Surgical R0 resection should be performed for solitary or confined liver or pulmonary metastases (II, A)

CS and HIPEC by experienced expert teams may improve progression-free survival (PFS) and overall survival (OS) for selected patients with PC (IV, B)

For most patients with good PS status and no significant comorbidities, the combination of infused regimens of 5-FU/leucovorin (LV) with either oxaliplatin (FOLFOX) or irinotecan (FOLFIRI) remains the recommended chemotherapy backbone for first-line treatment (I, A)

First-line chemotherapy selection should be based on prior oxaliplatin-based adjuvant treatment, clinical conditions and comorbidities, biologic drug to be combined, and patient’s preferences

Oxaliplatin and capecitabine combination is an alternative first-line treatment option for patients with mCRC (I, B)

In selected patients (i.e., with unresectable, low burden disease, slow tumor growth, mild symptoms, or frailty) a sequential therapy starting with FP or FP plus bevacizumab could be a valid option (I, B) [26–28]

Anti-EGFR antibodies should not be used without prior determination of RAS status. Expanded RAS analysis is superior to conventional RAS analysis (I, A)

Addition of anti-EGFR therapy to FOLFIRI and to FOLFOX improves PFS and OS in first-line treatment of patients with mCRC (II, A)

The addition of bevacizumab to chemotherapy is beneficial with respect to chemotherapy alone (I, B)

There is no clear evidence of the superiority of anti-EGFR over bevacizumab in combination with chemotherapy in the first-line treatment of mCRC

Anti-EGFR agents should not be combined with bevacizumab (I, B)

First-line treatment for fit patients with WT RAS mCRC should include a combination of chemotherapy doublet and a monoclonal antibody (anti-EGFR or bevacizumab)

First-line treatment for fit patients with mutant RAS mCRC should include a combination of chemotherapy doublet and bevacizumab (I, B)

Second and successive treatment lines should be individualized according to prior therapy, RAS status and clinical condition (II, C)

Patients with completely resected metastases should receive perioperatively 6 months of an active, preferably oxaliplatin-based chemotherapy regimen (I, B)

Fit patients with borderline resectable metastases should receive intensive induction therapy with chemotherapy doublets and a monoclonal antibody, or chemotherapy triplets with or without bevacizumab. In RAS WT tumors, anti-EGFR may be more effective than bevacizumab in terms of tumor shrinkage (II, B)

Fit patients with technically unresectable metastases and bulky, symptomatic or biologically aggressive disease, should receive intensive first-line therapy with chemotherapy doublets and a monoclonal antibody. In RAS WT tumors, bevacizumab may be subjectively better tolerated and allow the patient to receive more lines of therapy. Anti-EGFR agents, however, may be preferred in patients with significant tumor-related symptoms (IV, B)

Treatment de-escalation after induction therapy is often required due to cumulative toxicity, and is also acceptable once disease control is achieved (II, B)

Patients with unresectable metastases who are either unfit or asymptomatic and have limited risk for rapid clinical deterioration, should receive non-intensive/sequential therapy (I, B)