Reply to S.A. Kesikli et al
Authors: Jan Franko, Daniel Sargent, Axel Grothey
Journal: Journal of Clinical Oncology (2012)

rise to heterogeneity within these two groups as well as a misinterpretation of results, especially because of the lesser tumor burden in the nonpcCRC group in this study.It is typical to expect a shorter OS and DFS in a group with a lower tumor burden.In addition, the number of patients with operable or resectable hepatic and pulmonary metastases was not clear in the study.One cannot ignore the possibility that the patients within the nonpcCRC group might have more operable liver or pulmonary metastases than those within the pcCRC group.Indeed, patients with stage IV colorectal cancer constitute a heterogenous group in which the treatment approaches and survival rates differ between patients with solitary liver metastasis, multiple hepatic metastases, peritoneal metastases, and other extrahepatic metastases.A critical question here is whether this situation should lead to a change in the staging strategy or not.We know that a huge variation in the survival of patients with stage IV colorectal carcinoma exists. 2 The median OS is more than 2 years, and 5-year survival is around 10% for patients with mCRC.It was previously published in a different series that only approximately 15% of liver metastases were initially resectable. 3However, the use of modern chemotherapy and biologics, as well as advances in surgical techniques, have made it possible to render 10% to 40% of initially unresectable liver metastases resectable. 4,5Moreover, almost 23% of those patients could undergo curative-intent resections. 6Consequently, the percentage of patients suitable for curative surgery has increased.It has been reported that the amount of patients with a small burden of meta-staticdiseasewhocouldundergosurgicalresectionmightreachupto25% in selected patient cohorts. 7Today, it is well-known that the survival of a patient with CRC with a solitary resectable liver metastasis is better than that of a patient with stage III disease, reaching 25% to 50%, although this variesfromcentertocenter. 8Yet,itwasreportedrecentlythatthepresence of extrahepatic metastatic disease (EHD) such as peritoneal and/or pulmonary metastases concomitant to the liver metastases decreased the 5-year OS (28% v 55%). 9However, when EHD presented as a solitary pulmonary metastasis in patients with mCRC, the 5-year OS was much better than that of patients with EHD located at other disease sites (33% v 23%, respectively).In addition, Cao et al 10 recently reported that even hyperthermic intraoperative chemotherapy with or without early postoperative intraperitoneal chemotherapy in selected patients with pcCRC may increase the OS up to the levels observed in patients with CRC with liver metastases.Apparently, clinical evidence suggests that the current staging criteria for mCRC, although recently revised, do not reflect the variation in survival and prognosis. 11 In their recent validation study, Kim et al 12 demonstrated that the new stratified staging system provides essential prognostic information. 12However, there were no data regarding stage IV disease in this study, and it is remarkable that patients with stage IIIA disease had inexplicably better survival rates than patients with stage IIB and stage IIC disease.Therefore, we believe that a new staging system that reflects the survival differences and clinical experiences is necessary, especially for stage IV advanced colorectal cancers.Accordingly, we suggest that stage IV disease can be further subdivided into single resectable metastatic disease, single unresectable metastatic disease, and unresectable disease with peritoneal involvement.