Changing paradigms for liver resection of colorectal metastases.

Prometheus gave mankind wisdom and then suffered the consequences; his liver was eaten each night by eagles and regenerated each day. Surgeons educated by this tale have been resecting liver tumors for years and seeing improve- ment in patients' survival. The criteria for liver resection in patients with metastatic colorectal cancer have undergone a metamorphosis over the last 50 years with even broader boundaries. In Viganoet al.'s 1 article in this issue of the Annals of Surgical Oncology, another potential barrier to liver resection may have been lifted. They report that even for patients whose tumor progresses on chemotherapy, there is benefit from hepatic resection. Previous reports of resection in patients with tumor progression have had poor results. 2,3 Some of the studies may have been too small or had inadequate long-term follow-up. One such report ini- tially described poor results, but on further follow-up and with inclusion of more patients, the authors concluded that there was no difference in survival after liver resection between those whose tumor responded or progressed after neoadjuvant chemotherapy. This may reflect a cautionary tale about retrospective studies that are too small or do not report long-term follow-up. The strength of this report is that it is a large multi-institutional study. 1 Of the 2,143 patients undergoing hepatic resection, 176 patients expe- rienced tumor progression while on systemic neoadjuvant chemotherapy and still had a 35 % 5-year survival. How- ever, since the median follow-up is only 27 months, and most patients in the study were entered after 2006 with data collection stopping in 2010, the 5-year survival is only a projected number. If these results hold up after longer follow-up, Viganoet al.'s study would provide strong support for the use of regional therapy, in this case, hepatic resection, in patients with hepatic-only colorectal metas- tases. An MSKCC study, looking at the question of responders versus nonresponders to chemotherapy prior to liver resection reported no difference in survival in the two groups (59 vs 61 months for the responders vs progression, respectively), with a follow-up time of 63 months. 4 The MSKCC study was a single-institution study where 80 % of patients received postoperative (postop) therapy and 40 % postop hepatic arterial infusion (HAI). The patients whose tumor progressed in the MSKCC study were more likely to have positive margins when undergoing liver resection, a factor not reviewed in the Viganostudy. Vi- gano `'s report also stated that poor-risk patients (more than three metastases, lesions greater than 5 cm, or those with CEA higher than 200 ng/ml) should be treated with further chemotherapy prior to consideration of hepatic resection. Is further systemic chemotherapy useful? Second-line systemic chemotherapy has a low response rate averaging 20 % (range 11-35 %). 5 The median survival from starting second line treatment is about 11 months (range 9-14 months). 5 In Viganoet al.'s analysis, patients who progressed on chemotherapy with one negative factor such as more than three liver metastases have a 29.9 % 5-year survival when they undergo hepatic resection. The chances of being alive at even 3 years with further systemic therapy if a patient has tumor progression on first-line systemic chemotherapy and has poor risk factors is less than 1 %. Use of regional therapy with HAI after progression on systemic therapy may be a more useful approach. Using HAI oxaliplatin and systemic fluorouracil/leucovorin (FU/ LV), Ducreux et al. 6 observed a 64 % response rate in a group of patients where 81 % had not responded to prior systemic chemotherapy. At MSKCC, patients with unre- sectable disease who had received previous systemic chemotherapy and then received HAI-FUDR/dexametha- sone and systemic (SYS) oxaliplatin/irinotecan had a tumor response rate of 85 % with a median survival of 35 months from the time of initiation of HAI. 7 The major toxicities of