Rectal cancer and inflammatory bowel disease: natural history and implications for radiation therapy

There exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease (IBD). In addition, the tolerance of pelvic irradiation in these patients is unknown. We analyzed the largest series of patients with IBD and rectal cancer in order to determine the natural history of the disease as well as the effect and tolerance of pelvic irradiation.

A retrospective analysis of 47 patients with IBD and rectal cancer treated over a 34-year period (1960-1994) was performed. Thirty-five patients had ulcerative colitis and 12 patients had Crohn's disease. There were 31 male patients and 16 female patients. The stage (AJC) distribution was as follows: stage 0 in 5 patients, stage I in 13 patients, stage II in 7 patients, stage III in 13 patients, and stage IV in 9 patients. Surgical resection was performed in 44 patients. In two of these patients, preoperative pelvic irradiation was given followed by surgery. Twenty of these patients underwent postoperative adjuvant therapy (12 were treated with chemotherapy and pelvic irradiation and 8 with chemotherapy alone). Three patients were found to have unresectable disease and were treated with chemotherapy alone (2 patients) or chemotherapy and radiation therapy (RT) (1 patient). Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow-up ranged from 4 to 250 months (median 24 months).

The 5-year actuarial results revealed an overall survival (OS) of 42%, a disease-free survival (DFS) of 43%, a pelvic control rate (PC) of 67% and a freedom from distant failure (FFDF) of 47%. DFS decreased with increasing T stage with a 5-year rate of 86% for patients with Tis-T2 disease compared to 10% for patients with T3-T4 disease (p < 0.0001). The presence of lymph node metastases also resulted in a decrease in DFS with a 5-year rate of 67% for patients with NO disease compared to 0% for patients with N1-N3 disease (p < 0.0001). DFS decreased with increasing histopathologic grade with 5-year DFS rates of 71%, 52%, and 24% for grades 1, 2, and 3 respectively (p = 0.03). The T and N stages showed a statistically significant effect on pelvic control, with 5-year PC rates of 60% for Tis-2 versus 26% for T3-4 (p = 0.002) and 79% for NO versus 51% for N1-3 (p = 0.007). The histopathologic grade of the tumor did not significantly affect pelvic control. An analysis of high-risk patients (30) with T3-T4 or N1-N3 disease revealed at 5 years an OS of 9%, a DFS of 10%, a PC rate of 26%, and FFDF of 20%. In this subset of patients, there was a trend toward improved pelvic control in patients receiving RT (14 patients) with a 5-year PC of 60% compared to a rate of 23% for those patients not irradiated (16 patients). Acute complications (grade 3 or >) were noted in three patients (20%) receiving pelvic irradiation +/- chemotherapy and these included two cases of grade 3 skin reactions and one case of grade 4 gastrointestinal toxicity. Two patients (13%) developed small bowel obstruction at 2 and 4 months, respectively, postirradiation which were managed conservatively. There were no long-term complications in patients irradiated.

Treatment results are comparable to those historically reported for non-IBD-related rectal cancer although the subset of high-risk patients appeared to have a poorer outcome. In light of this finding and the ability of these patients to tolerate chemotherapy and pelvic irradiation, aggressive adjuvant therapy should be given to IBD-associated rectal cancer patients with high-risk features.