Multidisciplinary approach of colorectal cancer liver metastases

Table 1 Recommendations for perioperative and conversion therapy (adapted from ESMO 2016[110])

Perioperative treatment

It is defined by technical criteria for resection and prognostic considerations

It may not be necessary in patients with clearly resectable disease and favourable prognosis, in this case upfront resection is justified

It should administer FOLFOX or CAPOX to patients with resectable disease and unclear (probably unfavourable)

Targeted agents should not be used in resectable patients with prognostic indication for perioperative treatment

It should be considered when prognostic and resectability criteria are unclearly defined, and in patients with synchronous onset of metastases

Adjuvant chemotherapy is not strongly indicated for patients with favourable oncological and surgical criteria, who did not receive any neoadjuvant chemotherapy

Adjuvant chemotherapy is indicated for patients with unfavourable criteria

Adjuvant treatment with FOLFOX or CAPOX is recommended for patients who have not received any previous chemotherapy, unless patients already received oxaliplatin-based adjuvant chemotherapy

The choice of chemotherapy type should consider patients’ clinical conditions and therapy preferences

Conversion therapy

A chemotherapy regimen leading to high response rates and/or a large tumour shrinkage is recommended for potentially resectable patients

The best drug combination to use is still not clear because only few trials have addressed this issue:

RAS wild-type patients may benefit from a cytotoxic doublet plus an epidermal growth factor receptors agents antibody (best benefit/risk), and from the combination of FOLFOXIRI plus bevacizumab and, to a lesser extent, from a cytotoxic doublet plus bevacizumab

RAS mutant patients may benefit from a cytotoxic doublet plus bevacizumab or FOLFOXIRI plus bevacizumab

Patients must be re-evaluated regularly (every 2-3 mo) to prevent the overtreatment of resectable patients

Table 2 Conversion rates in colorectal cancer liver metastases after perioperative chemotherapy

Trial name	Chemotherapy type	Control	n	KRAS status	Overall response	Conversion to resection	R0 resection
BEAT[61]	FOLFOX/XELOX/FOLFIRI or fluoropyrimidines + bevacizumab	No	1914	Not selected	NA	11.80%	NA
First BEAT[62]	FOLFOX/XELOX + bevacizumab	Placebo	1914	Not selected	38%	11.80%	6.3% vs 4.9%
OPUS[70]	FOLFOX + cetuximab	FOLFOX	233	Wilde type	61% vs 37%	9%	4.7% vs 2.4%
POCHER[72]	Chr IFLO + cetuximab	No	43	Wild type	79%	60%	25.70%
PRIME[77]	FOLFOX + panitumumab	FOLFOX	591	Wild type	57% vs 48%	31% vs 22%	29% vs 17%
CELIM[11]	FOLFOX6 + cetuximab	FOLFIRI + cetuximab	106	Wild type	68% vs 57%	43%	38% vs 30%
BOXER[63]	CAPOX + bevacizumab	No	47	Not selected	78%	40%	NA
Loupakis et al[55]	FOLFOXIRI + bevacizumab	FOLFIRI + bevacizumab	508	Not selected	65% vs 53%	15% vs 12%	NA
Ye et al[73]	FOLFIRI + cetuximab	FOLFOX + cetuximab	177	Wild type	57% vs 29%	26% vs 7%	NA
CRYSTAL[71]	FOLFIRI + cetuximab	FOLFIRI	599	Wilde type	47% vs 39%	16%	4.8% vs 1.7%
OLIVIA[79]	FOLFOXIRI + bevacizumab	FOLFOX + bevacizumab	80	Not selected	81% vs 62%	61% vs 49%	49% vs 23%

CAPOX, XELOX: Capecitabine-oxaliplatin; NA: Not available; Chr IFLO: Chronomodulated irinotecan, 5-fluorouracil, leucovorin, and oxalipaltin; FOLFIRI: 5-fluorouracil, leucovorin and irinotecan; FOLFOX: 5-fluorouracil, leucovorin, and oxalipaltin; FOLFOXIRI: 5-fluorouracil, leucovorin, oxalipaltin and irinotecan.