To Resect or not the Primary Tumor in Metastatic Colorectal Cancer: Letter to the Editor

Abstract

Colorectal cancer (CRC) is one of the most common tumors in the US, Europe, and worldwide but with a relatively good prognosis. In the adjuvant setting, high long-term survival rates have been reported, and even in the metastatic setting, with the use of systemic chemotherapy the median survival time has been improved to roughly 20 months. The addition of biologic agents such as cetuximab or panitumab has raised expectation for further survival improvement. With these developments, an old problem in surgical oncology has now been updated. Is the decision to resect the primary tumor, when it is locally completely resectable, correct, or will resection harm patients with a stage IV disease? To highlight this critical question in day-to-day clinical practice, Stillwell et al. [1] performed a meta-analysis and reported the results in the April 2010 issue of this journal. The authors concluded that palliative primary tumor resection in metastatic CRC (mCRC) prolongs survival and benefits patients. Can this report be considered a practicechanging study? Multiple variables complicate robust conclusions and correct decisions about surgery for an individual patient with mCRC. These factors include the extent of metastatic disease, namely, unresectable liver metastasis and/or minimal or extensive peritoneal carcinomatosis and/or other distant metastases; locally advanced or potentially complete removal of the primary tumor; tumor responsiveness or resistance to chemotherapy; general status of the patient; and risk of surgery-related complications that may delay recovery from surgery. For example, a safe performance of a laparoscopic colectomy without morbidity allows rapid recovery and may overcome the problem of surgerydelaying chemotherapy. In the absence of randomized controlled trials (RCTs), Stillwell et al. identified eight retrospective studies, including one with 1062 patients with asymptomatic and minimally symptomatic mCRC. Median overall survival was 6.0 months longer in the primary tumor resection group compared with that in chemotherapy-alone group (RR = 0.55; 95% CI = 0.29– 0.82; p\0.001). Patients managed with chemotherapy alone were seven times more likely to have a complication from the primary tumor. The authors concluded that palliative resection of the primary tumor prolongs survival and reduces the risk of primary tumor-related complications. Although it is thought that meta-analyses provide the highest level of evidence, this study was limited by the inclusion of retrospective studies and their heterogeneity given that several confounding variables reported above were not considered. Moreover, four studies within this series found that there was no significant difference in survival with resection of the primary tumor. For improving overall survival in the metastatic setting, there is much hope with the advent of next-generation DNA sequencing technologies and their promise for completing the somatic mutations of major cancer types such as colorectal cancer and helping us understand how an individual tumor functions as a complete biological and molecular system. These advances may allow identification of novel biomarkers for tailoring new biologic therapies along with standard chemotherapy [2–14].