Colon cancer is a major public health problem. The primary treatment is resection. For patients with early-stage disease, surgery results in excellent survival rates. In contrast, patients with locally advanced tumors arising in "anatomically immobile" segments of large bowel have a less satisfactory outcome, in part secondary to compromised surgical clearance. Patterns-of-failure analyses suggest that for tumors that invade adjacent organs, exhibit perforation or fistula, or are subtotally resected, local failure rates exceed 30%. Multiple single-institution retrospective studies have shown improved local control and possibly survival with the addition of external irradiation and/or intraoperative radiation. In contrast, a recent Intergroup trial failed to show any benefit by the addition of adjuvant radiation therapy combined with chemotherapy. Interpretation of this trial's results is handicapped by low patient accrual. With the advent of novel and more effective systemic therapies for metastatic colon cancer, current and future clinical research will address the efficacy of these agents in the adjuvant setting. Adjuvant radiation therapy should be considered in patients with colon cancer at high risk for local failure.
Dr. Willett and his colleagues present a thoughtful analysis of the potential use of adjuvant radiation in a subset of patients with colon cancer. Despite a compelling rationale, the only randomized trial (under the leadership of Dr. Willett) failed to show benefit. As the authors comment, interpretation of this "negative trial" must be guarded, since patient accrual was too low to reliably rule out a meaningful benefit. The single-institution studies with historical controls have limited usefulness in providing efficacy evidence for clinicians. However, such historical data do demonstrate that some patients will develop locoregional recurrence. Components of "abdominal recurrence" may include local (from direct extension), extended regional nodes (root of mesentery, periaortic), liver metastases, or peritoneal seeding. From a cancer biology perspective, patients with gross or microscopic residual local disease, particularly those who are node-negative, may well gain a survival benefit from adjuvant radiation.
Defining the small subset of patients to consider for adjuvant radiation will require careful communication between the surgeon and the pathologist, followed by detailed discussion with consultants in medical oncology and radiation medicine. The types of patients who may benefit are best articulated by some examples.
Right Colon Cancer With Posterior Penetration
The posterior aspect of ascending (and descending) colon is contiguous with the retroperitoneum. In the case of right colon cancer with posterior penetration, the pathologic stage most commonly will be T3, although if tumor directly invades the kidney, it would be T4. A T3 anteriorly located cancer is invasive only into the subserosa and is at little risk of a local recurrence. A T4 anterior tumor is at risk for peritoneal failure. If the patient has a posterior grossly transmural T3 cancer, with either a positive radial margin or a clear margin less than 1 mm, adjuvant radiation therapy should be considered. The challenge will be to define the "at-risk" field. A preoperative computed tomography scan (as well as clips placed by the surgeon to define the site) may be useful.
Abdominal Wall Adherence
Sigmoid or transverse colon cancers may be adherent to the anterior abdominal wall secondary to inflammation or direct invasion from a T4 cancer. Some patients will have gross perforation into the abdominal wall. Wide surgical excision may be adequate to prevent an abdominal wall recurrence, but a small subset of such patients may benefit from localized radiation therapy. Consultation among the surgeon, pathologist, and radiation therapist is essential in such cases.
Pelvic Bladder or Sidewall Adherence
Sigmoid colon cancer may be adherent/invasive to pelvic organs or the pelvic sidewall. Extended surgical resection of contiguous organs may suffice to minimize the risk of local recurrence. However, bladder invasion with its rich lymphatics poses a high risk for local recurrence. A mobile cancer adherent to the pelvic sidewall may result in a nil or minimal radial margin, suitable for adjuvant irradiation.
Adjuvant chemotherapy is clearly beneficial for node-positive and high-risk node-negative colon cancer patients. As described above, a small subset of patients will have minimal or positive radial margins contiguous to a well-defined part of the abdominal cavity. Consideration should be given to chemoradiation therapy in such patients if the "high-risk" site can be identified, and the extent of nodal or distant spread is such that the prevention of an isolated local recurrence will likely benefit the patient's quality of life or overall survival.
-Alfred M. Cohen, MD, FACS,FASCRS
The author has no significant financial interest or other relationship with the manufacturers of any products or providers of any service mentioned in this article.