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Combination Procedures Improve Outcomes in Colorectal Cancer

A diagram of laparoscopic colon resection.
Photo courtesy of www.columbiasurgery.org

NewYork-Presbyterian Hospital has taken a leadership role in clinical innovations that are improving outcomes and lessening the risks of therapy in colorectal cancer. Radical resections, for example, are being replaced with several different types of minimally invasive procedures. At the same time, some of the newer targeted medical therapies are dramatically building on the efficacy of conventional chemotherapy with very tolerable side effects.

"In colorectal cancer, we are now moving to less radical surgical procedures with adjuvant chemotherapies that provide rates of cancer-free survival that are at least as good as those achieved previously but with less trauma," noted Alfred I. Neugut, MD, PhD.

Within the goal of reducing the morbidity of radical resections, among the most exciting developments has been the use of a combination laparoscopy and colonoscopy procedure to reach lesions that would be difficult to treat with either alone. One of the key innovators of this approach, Jeffrey W. Milsom, MD, said that the combined approach became possible when he and his co-investigators introduced insufflation with carbon dioxide (CO₂) to largely eliminate the distension normally produced by colonoscopy using room air.

"We found that we had a very high success rate performing laparoscopy and colonoscopy together, and this was very well tolerated by the patients," he noted. "This is an example of an important fusion of technologies that permits lesions to be treated from the inside of the bowel using backup support from the peritoneal cavity using minimally invasive or laparoscopic techniques. For example, in a patient with a difficult polyp in the right colon that is unresectable by colonoscopy, laparoscopy can be employed to position the lesion so that it can be removed by the colonoscope. This provides the least amount of trauma without loss of surgical precision."

Initially, according to Dr. Milsom, there was concern that insufflation with CO₂ could dangerously alter the acidbase balance of the body. However, preclinical studies and clinical studies have demonstrated a very high level of safety using the combined technique. The only drawback is that it requires both an endoscopist and a laparoscopist.

"With this combined procedure, a bowel resection is avoided and no more than an overnight stay is required," Dr. Milsom said. "Currently, this approach has a limited application for benign or very early malignant lesions, but this is only the beginning. I believe that in the future, more difficult lesions, including difficult malignant lesions, will be treated in this fashion."

Laparoscopy has been widely incorporated into colon cancer resections at many centers, but the surgeons at NewYork-Presbyterian Hospital have sought to consider variations when appropriate. One such variation has been hand-assisted laparoscopy, which can have numerous advantages when employed in the right patient.

Richard L. Whelan, MD

"The hand-assisted approach requires a longer incision than most pure laparoscopic operations," explained Richard L. Whelan, MD. "However, we recognized that some patients undergoing laparoscopy already receive incisions large enough to insert a hand. In many cases, a hand can facilitate resection, including mobilization of tissue, without greatly detracting from the advantages of the minimally invasive approach."

Some patients need large incisions because they have large tumors that require a significant abdominal wall incision in order to remove the specimen. Obesity is also an issue; obese patients often require longer fascial incisions to permit specimen extraction. In a review of obese patients from NewYork-Presbyterian/Columbia who underwent straight laparoscopic resection, a substantial percentage had a final incision between 7 cm and 11 cm long, which is large enough to permit hand-assisted laparoscopy. Very tall or muscular patients are also likely to require larger incisions during minimally invasive resection. Thus, in these 3 groups of patients, who together represent almost 40% of all surgical candidates, the advantages of hand-assisted laparoscopy can be obtained without substantially increasing the abdominal wall trauma when compared with straight laparoscopic methods.

"We look for patients in whom a large incision would likely be needed and then use the hand-assisted approach from the outset. We now have data to support this approach," said Dr. Whelan, referring to a 5-center study that included investigators at NewYork-Presbyterian Hospital.

Presented at a recent meeting of the American Society of Colon and Rectal Surgeons, the study randomized 97 patients to laparoscopy alone or handassisted laparoscopy for left and total colectomy. For hand-assisted laparoscopy compared with laparoscopy alone, the average duration of the procedure was 33 minutes shorter for left colectomy and almost an hour less for total colectomy. There was no significant difference in recovery time, amount of pain medication required, or length of stay. The average incision length was 6.1 cm for laparoscopy alone but only 8.2 cm for the hand-assisted approach.

"The hand-assisted approach is contraindicated for small or low BMI patients because the hand incision represents a much larger percentage of their abdominal wall and the larger incision is usually not required for specimen extraction," noted Dr. Whelan. "We believe hand-assisted methods are very useful when employed selectively."

In adjuvant therapies, there have also been significant developments. While several combination chemotherapy regimens, such as FOLFOX (5-fluorouracil, eucovorin, and oxaliplatin) and FOLFIRI (5-FU), leucovorin, and irinotecan are now widely employed to extend survival in advanced colorectal cancer, recent excitement has been generated by the monoclonal antibodies, such as bevacizumab, which inhibits vascular endothelial growth factor (VEGF) and is already a standard as first-line treatment for stage IV disease. This and other monoclonal antibodies, particularly cetuximab, an inhibitor of the epidermal growth factor receptor (EGFR), are now being tested in the adjuvant setting. Investigators recently tested bevacizumab and cetuximab in combination for stage IV colorectal cancer.

"We recently presented a Phase II paper that we conducted with the New York Cancer Consortium. We treated almost 70 patients with the FOLFOX regimen in combination with bevacizumab and cetuximab and observed an excellent response rate with acceptable toxicity," said Joseph T. Ruggiero, MD. "This double antibody approach in combination with chemotherapy is going into more advanced testing and may represent an important direction for future management."

"Evaluating FOLFOX with and without bevacizumab will answer one of the most pressing questions about optimal adjuvant therapy," added Dr. Neugut.

"It is an exciting chapter for patients from the surgical side as well," added Dr. Milsom. "Now more than ever we have treatment options we can offer patients and with much, much safer outcomes."

Editor's Note: All of the physicians featured in the article participated in the "Advances in Colorectal Cancer Therapies" web cast on June 20, 2007. The web cast can be accessed at: www.nypcancer.org.