NCCN Presents Updated Colorectal Cancer Guidelines

FORT LAUDERDALE, Fla—More patients are candidates for sphincter-saving operations under the revised National Comprehensive Cancer Network (NCCN) practice guidelines for rectal cancer.

For colon cancer, the updated guidelines eliminate routine computed tomography (CT) scans for surveillance after treatment and remove levamisole as a chemotherapeutic agent. Recent studies have also strengthened the NCCN recommendation for the use of laparoscopic surgery as an option for the treatment of polypoid cancer and invasive cancer.

The revised NCCN practice guidelines for colorectal cancer were presented by Paul F. Engstrom, MD, senior vice president for populations science, Fox Chase Cancer Center, and professor of medicine, Temple University; Krystyna Kiel, MD, assistant professor of radiology, Robert H. Lurie Comprehensive Cancer Center of Northwestern University; and John M. Skibber, MD, associate professor of surgical oncology, M.D. Anderson Cancer Center. They spoke at the NCCN’s Fifth Annual Conference.

Rectal Cancer Guidelines

The NCCN guidelines for the primary treatment of rectal cancer allow for a variety of options. Dr. Engstrom encouraged the medical team to include the patient when choosing a treatment pathway. “It’s truly a multidisciplinary discussion, with the patient involved in the decision-making,” he said.

The revised practice guidelines for rectal cancer now recommend that clinicians consider lesions within 10 cm of the anal verge for local excision if they are also less than 40% of the circumference of the bowel and less than 4 cm in size. The lesions must also be mobile and nonfixed.

The guidelines recommend the use of endorectal ultrasound to determine the extent of disease in the workup for rectal cancer. In previous guidelines, endorectal ultrasound was a “category 2” recommendation, meaning that it was judged “somewhat controversial” by the committee.

Endorectal ultrasound, which is 70% to 90% accurate for T stage disease, is “at its best when determining whether disease is confined to the bowel wall (T1 or T2 tumor) or whether it goes through the bowel wall (T3),” Dr. Skibber said.

The workup must also include pathology review. “Pathology review is important if local excision is being considered, because it should not be considered for patients with poor differentiation, lymphatic or vascular invasion, and poor prognostic signs” Dr. Skibber said.

Preoperative Therapy

The majority of patients with fixed lesions or multivisceral involvement should be treated with preoperative chemotherapy and radiotherapy, Dr. Skibber said. The guidelines recommend continuous or bolus fluorouracil (5-FU)/radiotherapy followed by resection.

Interest in preoperative radiation is growing, Dr. Kiel said, as it induces a reduction in tumor size that results in an increase in sphincter-saving operations and a decrease in small bowel morbidity.

Further trials will show whether downstaging affects survival and whether the clinician can make postoperative decisions based upon preoperative responses, Dr. Kiel said. “I think we will see a trend toward preoperative radiation now that we have endorectal ultrasound to provide more accurate staging.”

Patients with advanced metastatic disease can be managed nonsurgically with stenting, laser photocoagulation, or 5-FU/radiotherapy, Dr. Skibber said.

Recent trials have clearly shown that after primary treatment, chemotherapy in addition to radiation improves survival. “Adjuvant therapy for rectal cancer is changing,” Dr. Engstrom said. The recommendations in the updated guidelines for adjuvant therapy for T1-3, N1-2, or T3, N0 disease now carry a “category 1” designation, which means the recommendation is based upon high-level evidence.

In these studies, “it was the addition of chemotherapy to radiotherapy that really had an impact on outcomes,” Dr. Kiel said. The North Central Cancer Treatment Groups (NCCTG) examined radiotherapy alone vs radiotherapy with 5-FU. They found that with the addition of 5-FU chemotherapy, local failure decreased and survival increased. “As long as it’s 5-FU based chemotherapy, you’re fine,” Dr. Kiel said.

Recurrences

When patients undergo surgery for locally recurrent cancer, they should be considered for 5-FU/radiotherapy if not given previously, Dr. Skibber said.

The guidelines have also added a treatment pathway for patients who have an isolated pelvic recurrence. The guidelines recommend preoperative bolus or continuous IV 5-FU plus radiotherapy and resection, if feasible. Dr. Skibber cited a study that found 21% to 58% 5-year survival for patients with local recurrence who underwent resection.

Colon Cancer Guidelines

For the treatment of colon cancer, the NCCN guidelines now offer two surgical options: colectomy with en bloc removal of regional lymph nodes (sometimes referred to as hemicolectomy) or lapa-roscopic surgery if a protocol is available. This is a stronger recommendation than the previous guidelines, which designated laparoscopic surgery as a “category 2” recommendation.

To explain the recommendation, Dr. Skibber showed the results of 12 studies published between 1993 and 1998 that compared open surgical techniques with laparoscopy. In studies that examined lymph node harvest, laparoscopic surgery retrieved an average of 11.3 lymph nodes vs 11.0 for open techniques.

The Clinical Outcomes of Surgical Therapy group is currently conducting a trial that randomizes patients between open colectomy and laparoscopic colectomy. This trial will look at port site recurrence, a specific concern in laparo-scopic surgery, as well as short-term survival, Dr. Skibber said. “In the short term, at least, there doesn’t appear to be any obvious difference in survival,” he said. “Our recommendation is that patients who undergo laparoscopy be put in that clinical trial.”

Adjuvant Therapy

Recommendations for adjuvant therapy that included levamisole as one option for patients with stage II (T4, N0) or stage III (any T, N1-2) cancers have been changed. The use of 5-FU/levamisole “fell by the wayside” based on newer data, Dr. Engstrom said. The NCCN guidelines now recommend 5-FU/leucovorin with or without radiotherapy.

“An issue that continues to be a concern to the committee is the role of radiotherapy in colon cancer,” Dr. Engstrom said. Unfortunately, the prospective trial that was intended to evaluate radiation therapy as an adjuvant for colon cancer was stopped because of accrual problems, Dr. Kiel said.

However, retrospective studies suggest that while “there is no benefit for [Duke’s] B2 lesions, for B3 lesions, radiotherapy did improve local control and survival.” These limited retrospective studies suggest the use of radiation, but the physician should evaluate each patient individually, she said.

In patients who present with liver metastases and undergo liver resection for possible cure, it’s important to consider postoperative treatment, Dr. Engstrom said. The guidelines list several options. “Right now, the committee feels that if it’s appropriate, the patient should have intrahepatic artery infusional therapy along with systemic therapy,” Dr. Engstrom said.

Irinotecan in Combination

Irinotecan (Camptosar), for the first time, is being recommended for use as part of a chemotherapy combination in patients with advanced but potentially controllable disease. This option is based on a study presented at the 1999 ASCO meeting.

“We’re not recommending 5-FU/leucovorin/irinotecan as standard adjuvant therapy for your Duke’s C colon cancer patients, but in those patients with stage IV disease, there was evidence from that report that patients had a longer disease-free survival, although not necessarily longer overall survival,” Dr. Engstrom said. “The data are not in on that yet.”

The NCCN committee has removed the use of routine CT scans of the abdomen for surveillance after primary treatment for colon cancer. “There are no data to show that doing prospective CT scans enables a clinician to pick up an earlier, more operable lesion,” Dr. Engstrom said. The use of chest x-rays has also been eliminated.

The committee followed the American Society of Clinical Oncology (ASCO) recommendations for the use of carcino-embryonic antigen (CEA) screening: every 3 months for 2 years, then every 6 months for 3 years. “The biggest problem is when you have a rising CEA but your work-up is negative,” Dr. Engstrom said.

A Negative Workup

The committee disagreed somewhat over how to handle a negative workup. In that situation, the guidelines recommend repeating CT scans every 3 months. At this time, the value of using newer imaging techniques, such as PET (positron emission tomography), in the workup is unproven, Dr. Skibber said. He had other reservations as well. “My concern as a surgeon is that they tend to be rather poor in terms of anatomic location,” he said.

When patients have evidence of resectable disease on conventional imaging, surgical exploration can be considered, Dr. Skibber said. He cited one study in which second-look operations were performed on 72 patients after recurrences were detected by CEA monitoring and imaging techniques.

Only one patient had no detectable disease in the second-look operation; 39 patients had all of their disease resected. The resectable group had a significantly better 5-year survival than the unre-sectable group (41.3% vs 5.2%).