Adjuvant radiation therapy for rectal carcinoma: predictors of outcome

To review predictors of outcome, including sequencing of modalities and pretreatment findings for adjuvantly treated rectal cancer.

From 1975 through 1990, 307 patients with adenocarcinoma of the rectum underwent adjuvant radiation therapy. In 251 cases the radiation therapy was administered preoperatively, either 40-50 Gy (median dose 45 Gy) followed in 6-7 weeks by surgery (210 cases), or 20 Gy in five fractions immediately prior to surgery (41 cases). In 56 cases, patients were referred postoperatively for radiation (median dose 50 Gy). Adjuvant chemotherapy was never given concurrently with the preoperative radiation (RT), although 43 of the cases (including 14 of the preoperative RT cases) received postoperative chemotherapy.

Multivariate analysis (Cox model) indicated that significant predictors of better overall freedom from disease were preoperative rather than postoperative RT (p < 0.001), low surgical stage (p < 0.0001), specialist surgeon (p = 0.007), low or moderate histologic grade (p = 0.026), and proximal lesion (p = 0.033). The significant predictors for better local control included use of preoperative RT (p < 0.001), low or moderate grade (p = 0.001), and low surgical stage (p = 0.015). The 5-year local control and freedom from disease for the preoperative RT patients were 90% +/- 2% and 73% +/- 3%, respectively. The selected cases that received the short course of 20 Gy preoperatively did well. Although 24 out of 41 patients proved to have Astler Coller B2 or C disease, local control at last follow-up was 39 out of 41 (95%). A second multivariate analysis of pretreatment factors was performed on the preoperative RT cases. The significant factors for both local control and overall freedom from disease were noncircumferential vs. circumferential tumor, proximal vs. distal lesion, and background of the surgeon. Additional negative factors on univariate analysis (although not achieving independent significance on multivariate analysis) included the finding of near-obstructing lesions and elevated carcinoembryonic antigen (CEA). Grade > or = 3 sequelae occurred in 8% of cases (including 3% bowel obstruction). The only significant factor for complications was background of the surgeon (4% for colorectal specialists vs. 12% for nonspecialists, p = 0.015).

Significant factors for better tumor control included preoperative as opposed to postoperative RT and the experience of the surgeon. In selected cases, excellent results can be obtained with a short course of preoperative radiation. Concurrent chemotherapy need not be given routinely with preoperative radiation. Subgroups of preoperative RT cases at risk for distant metastases (who might benefit from postoperative chemotherapy), and at high risk for local failure (for whom concurrent preoperative chemotherapy and radiation might be considered), are identified.