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Original Article |
Helen F. Graham Cancer Center, 4701 Ogletown-Stanton Road, Newark, Delaware 19713
Correspondence: Address correspondence and reprint requests to: Nicholas J. Petrelli, MD; E-mail: npetrelli{at}christianacare.org.
In this new section of the Annals of Surgical Oncology, entitled "Controversies in Surgical Oncology," the present topic is "Treatment of Synchronous Colorectal Metastases in the Asymptomatic Patient: Resection of the Primary Tumor With Postoperative Chemotherapy or Immediate Neoadjuvant Chemotherapy." I will take the prochemotherapy position and defend the fact that in this group of asymptomatic patients who present with a primary colorectal cancer in the presence of distant metastases, it is not necessary to perform surgery on the primary tumor. This is especially the case in the presence of unresectable distant metastases.
Sometimes the hardest decision to make in surgical oncology is when not to operate on a patient. A major goal of therapy in patients with unresectable colorectal distant metastases is the maintenance of quality of life. Surgery in general, but, for that matter, any treatment, should be judged on the basis of the e7ects of such therapy on tumor-related symptoms and complications. The results of potential side effects of treatment on the overall quality of life should also be considered. Advocates of up-front resection of the primary colorectal cancer have stated that these cancers left in situ will progress to complications that consist of perforation, hemorrhage, or obstruction, which lead to emergency surgery and subsequent high morbidity and mortality.1,2 However, to counteract this argument, recent reviews have demonstrated that the potential complications of leaving the primary tumor intact have been overstated and seem limited to risks of colonic obstruction in the range of 10% to 20%, gastrointestinal hemorrhage (4%), and fistula formation (4%).3–5 A recent article by Tebbutt et al.4 compared the incidence of major intestinal complications in patients who received chemotherapy treatment with or without prior palliative resection of the primary colorectal cancer. They reported that the obstruction rate of 13% was identical in patients who underwent initial resection of the primary cancer compared with those with the primary tumor left in situ. This is because patients who underwent initial resection with metastatic disease experienced adhesive bowel obstruction and obstruction related to peritoneal recurrence. In a retrospective review from Vanderbilt University Hospital, Scoggins et al.5 postulated that resection of a primary colorectal cancer could be avoided safely in a select population of asymptomatic colorectal cancer patients with incurable stage IV disease. Only 2 (8.7%) of 23 patients treated without resection developed obstruction at the primary tumor site that necessitated emergent colon diversion. There were no episodes of tumor-related hemorrhage or perforation. Noteworthy was the fact that in the group of patients who underwent resection of the primary cancer, the operative morbidity was 30.3%, and the perioperative mortality was 4.6%. The data also demonstrated no difference in overall survival between the group of patients who underwent primary tumor resection and the group treated nonoperatively. Both groups were well matched in terms of metastatic tumor burden and did not include patients with isolated hepatic or pulmonary metastasis amenable to surgical resection.
Another important recent development in the treatment of metastatic colorectal cancer provides a basis for not resecting the primary cancer in the presence of distant metastasis, especially unresectable distant metastases. This relates to the improvements made in chemotherapy over the past several years in terms of newer systemic chemotherapeutic agents along with targeted therapies. Under these circumstances, the primary cancer may never become symptomatic.
A second major development that can avoid surgical resection of the primary cancer derives from increasing success in the management of intestinal obstruction or hemorrhage by using endoscopic techniques. In such circumstances, tumors causing intestinal obstruction can be successfully palliated by using stents inserted under fluoroscopic or colonoscopic guidance. As definitive palliative treatment, >90% of stents remain patent after 6 months of follow-up.6 Similarly, endoscopic ablative therapies may be useful in controlling both obstructive and bleeding symptoms. These may include endoscopic laser therapy, such as the neodymium–yttrium aluminum garnet laser, cryotherapy, transanal resection for rectal cancers, or photodynamic therapy.7
Nevertheless, all of the previously described studies were retrospective. There exists only a single small prospective trial of 24 patients that evaluated chemotherapy alone with expectant surgery for development of symptoms for stage IV colorectal cancer patients with an asymptomatic primary cancer. This trial, like the retrospective reviews mentioned previously, also found a low incidence of obstruction (17%) in patients who did not undergo initial primary tumor resection.8 It is interesting to note that these lower-than-anticipated risks of complications related to the intact primary cancer have all been reported in series for which systemic chemotherapy consisted of 5-fluorouracil and leucovorin alone. As stated previously, with the newer chemotherapeutic and targeted agents, it is possible that patients with advanced disease and an asymptomatic primary tumor may be even less prone to obstruction than currently reported. These patients may be spared the need to undergo major surgery and its potential associated complications at a time when treatment should focus on quality of life.
Finally, because the data to support not resecting the primary tumor in this group of patients are retrospective, it is important that prospective data be obtained. In view of this, the National Surgical Adjuvant Breast and Bowel Project has formulated a phase II trial under the leadership of Larry McCahill, MD, from the University of Vermont. It is entitled "A Phase II Trial of 5-Fluorouracil, Leucovorin, and Oxaliplatin Chemotherapy Plus Bevacizumab for Patients With Unresectable Stage IV Colon Cancer and Synchronous Asymptomatic Primary Tumor." This prospective trial will deal only with colon cancer and not rectal cancer. The primary end point is the event rate related to the intact primary tumor requiring surgery—that is, the rate of hemorrhage, perforation, fistula formation, and obstruction. The secondary aim of this trial is to record any event related to the intact primary colon cancer that necessitates hospitalization, blood transfusions, or endoscopic stent placement. Hence, this trial will establish baseline safety and efficacy data for treating patients who initially present with surgically incurable stage IV colon cancer with an intact, yet asymptomatic, primary tumor. The specific hypothesis of this trial is that the elimination of initial surgery for patients receiving the previously described chemotherapy and targeted agent will not lead to unacceptable morbidity related to the intact primary tumor. This prospective phase II trial should shed light on this particular controversy in surgical oncology. However, until we have the results of this trial, it seems that patients who present with no symptoms associated with the primary colorectal cancer in the presence of unresectable stage IV disease can safely undergo nonoperative management, which allows for prompt initiation of systemic disease-directed therapy. It is important to remember that these patients require continual careful observation in terms of their intact primary cancer, with detailed patient counseling and efficient communication between the medical and surgical oncologists.
Received for publication June 16, 2005. Accepted for publication August 11, 2005.
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