What Is the Best Treatment for Stage IV Colorectal Cancer

For decades, clinicians have seen patients who present with extensive stage IV colorectal cancer, frequently with hepatomegaly, weight loss, and poor performance status. Such patients receive supportive care or, if performance status allows, a trial of systemic chemotherapy. With the increased use of preoperative imaging, clinicians are now seeing many patients who present with asymptomatic or minimally symptomatic stage IV colorectal cancer. Management of such patients lacks a significant evidence base. Cook et al. have used the Surveillance, Epidemiology, and End Results (SEER) database from 1988 to 2000 to analyze the patterns of care of such patients. The authors have thoughtfully analyzed these population-based data and have carefully couched their conclusions with appropriate caveats. The data are quite clear in demonstrating that most patients undergo surgical resection of their primary tumors despite the presence of unresectable distant disease—hence, palliative surgery. The SEER data are incomplete in pivotal areas, and this invalidates comparisons of up-front operation versus systemic chemotherapy followed by surgical resection only for subsequent obstruction, perforation, or hemorrhage. The median survival for initial-resection patients was 11 months, compared with 2 months for those who did not undergo resection. These differences suggest that the groups were vastly different with regard to the extent of disease and comorbidities; these elements are not captured in the SEER database. In addition, many patients who present with stage IV disease have the diagnosis made at the time of primary tumor resection, at which time the decision for resection has already been made. The authors clearly define the key arguments: elective operations have a much lower morbidity and mortality than emergency operations, so we should remove the primary tumor and then proceed with chemotherapy with hopes for a good response. However, additional issues relevant to this paradigm are that (1) initial operative intervention (with or without laparoscopic-assisted resection) delays systemic chemotherapy; (2) with recent advances in systemic therapies, median survival with metastatic disease approaches 2 years; (3) it is likely that response at metastatic sites will also be associated with tumor regression at the primary tumor site; and (4) obstruction is uncommon with proximal cancers. We do not know the natural history of unresected primary tumors in patients receiving state-of-the-art chemotherapy who survive 2 to 3 years with initial stage IV cancer. In the absence of prospective clinical data (either randomized or a broad cohort of well-defined clinical and tumor data), stage IV colorectal cancer patients may be treated on the basis of the extent of metastatic disease, comorbidities, location of the primary tumor, symptoms related to the primary tumor, age, and the desire for and likelihood of tolerating systemic chemotherapy. My personal management algorithm is summarized in Table 1. Rectosigmoid and rectal cancer patients are more problematic than those with colon cancer. Abdominoperineal resection is not an attractive palliative operation. Six weeks of radiotherapy may stop or prevent bleeding, but it is time-consuming and uncomfortable. The main clinical challenge is the large cohort of patients with stage IV disease and asymptomatic or minimally symptomatic distant Received March 15, 2005; accepted April 17, 2005; published online June 16, 2005. Address correspondence and reprint requests to: Alfred M. Cohen, MD, FACS, FASCRS; E-mail: acohen@email.uky.edu.