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

Purpose: There exists little information concerning the natural history of rectal cancer in patients with inflammatory bowel disease (IBD). In additio n, the tolerance of pelvic irradiation in these patients is unknown. We ana lyzed 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 tol erance of pelvic irradiation. Methods and Materials: A retrospective analysis of 47 patients with IBD and rectal cancer treated over a 34-year period (1960-1994) was performed. Thi rty-five patients had ulcerative colitis and 12 patients had Crohn's diseas e. There were 31 male patients and 16 female patients. The stage (AJC) dist ribution was as follows: stage 0 in 5 patients, stage I in 13 patients, sta ge 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 th ese 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 chem otherapy alone (2 patients) or chemotherapy and radiation therapy (RT) (1 p atient). Radiation complications were graded using the RTOG acute and late effects scoring criteria. Follow-up ranged from 4 to 250 months (median 24 months). Results: 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 incre asing T stage with a 5-year rate of 86% for patients with Tis-T2 disease co mpared 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 rat e of 67% for patients with NO disease compared to 10% for patients with N1- N3 disease (p < 0.0001). DFS decreased with increasing histopathologic grad e with 5-year DFS rates of 71%, 52%, and 24% for grades 1, 2, and 3 respect ively (p 0.03). The T and N stages showed a statistically significant effec t on pelvic control, with 5-year PC rates of 60% for Tis-2 versus 26% for T 3-4 (p = 0.002) and 79% for NO versus 51% for N1-3 (p = 0.007). The histopa thologic 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 a t 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 i n 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 complic ations (grade 3 or >) were noted in three patients (20%) receiving pelvic i rradiation or chemotherapy and these included two cases of grade 3 skin rea ctions and one case of grade 4 gastrointestinal toxicity. Two patients (13% ) developed small bowel obstruction at 2 and 4 months, respectively, postir radiation which were managed conservatively. There were no long-term compli cations in patients irradiated. Conclusion: Treatment results are comparable to those historically reported for non-IBD-related rectal cancer although the subset of high-risk patient s appeared to have a poorer outcome. In light of this finding and the abili ty of these patients to tolerate chemotherapy and pelvic irradiation, aggre ssive adjuvant therapy should be given to IBD-associated rectal cancer pati ents with high-risk features. (C) 1999 Elsevier Science Inc.