Reply to D.J. Gallagher et al
Authors: Jean-Nicolas Vauthey, Daria Zorzi, Scott Kopetz, Eddie K. Abdalla, Yoji Kishi, Dan G. Blazer
Journal: Journal of Clinical Oncology (2009)

We would like to thank Gallagher et al 1 for their interest in our article. 2In our study, 194 (64.6%) of 305 patients received postoperative chemotherapy, and there was no difference in the distribution of these patients among the three groups with complete, major, and minor response (52%, 70%, and 63%, respectively; P ϭ .2).When postoperative chemotherapy was included in a landmark analysis of overall survival, it was not found to be a predictor of overall survival (P ϭ .73;hazard ratio, 0.93; 95% CI, 0.61 to 1.42).For this reason, the variable was not considered further in multivariate analysis.As usual methods lead to biased estimates of survival, we utilized a landmark analysis at 12 weeks after surgery, a time point by which approximately 90% of adjuvant-treated patients had initiated treatment. 3Median survival and 5-year survival for the patients who received adjuvant chemotherapy within 12 weeks of surgery was 55 months and 42%, respectively, versus 52 months and 46%, respectively, for the patients who did not receive adjuvant chemotherapy (Fig 1).In our series, most patients presented with resectable colorectal liver metastases (CLM); these patients typically undergo 2 to 3 months of preoperative chemotherapy followed by 2 to 4 months of postoperative chemotherapy with a total of 6 months of perioperative chemotherapy. 4These data raise the question as to whether postoperative chemotherapy is necessary at all in the treatment of patients with CLM who have received preoperative chemotherapy.Our study reflects the problematic issue that postoperative chemotherapy cannot always be given to patients, frequently as a result of protracted postoperative recovery.A similar issue emerged in the randomized study by Nordlinger at al, 5 where 37% of patients did not receive postoperative chemotherapy in the perioperative chemotherapy arm of the study.In contrast, preoperative chemotherapy can be given consistently to most patients and assists in the selection of patients who most benefit from treatment.Preoperative chemotherapy may also minimize the risk of nontherapeutic laparotomies reported in patients who undergo surgery up front (11% with surgery up front v 5% with perioperative chemotherapy). 5Other data from our group, reporting on the pathologic response to oxaliplatin combined with bevacizumab, suggest that extended chemotherapy (Ͼ 4 months) is not more effective than limited chemotherapy. 6In addition, we previously showed an association among irinotecan, steatohepatitis, body mass index, and surgical outcome. 7More recently, we showed that extended preoperative chemotherapy combining oxaliplatin and bevacizumab (ie, Ն nine cycles) is associated with an increased risk of hepatic insufficiency after resection of CLM. 8 Taken together, it is equally important to select preoperative chemotherapy appropriately and to consider the negative effect of protracted chemotherapy.Gallagher et al also refer to a high postoperative mortality but misquote our article, which indicates 3% or 8 deaths (misquoted as 8%) within 60 days.This perioperative mortality is comparable to the perioperative mortality rate (2.8% to 3.1%) reported for hepatic re-section of CLM at other major centers that do not advocate the use of preoperative chemotherapy before surgery. 9-13