Delayed toxicity of brief preoperative irradiation and risk-adjusted postoperative radiotherapy of operative rectal carcinoma. Results of a randomized prospective study

Analysis of a randomized study of preoperative radiation therapy for operable carcinoma of the rectum with regard to late sequelae. Results of tumor control and survival, which have already been published in detail are summarized for comparison and for confirmation of the conclusions. Between January 1988 and October 1993 94 patients with operable carcinoma of the rectum were included in a randomized trial. Fourty-seven patients were treated with 5 x 3.3 Gy (field size 16 x 16 cm, 9 MeV photons) 24 to 48 hours prior to surgery; 46 patients did not receive preoperative irradiation. If risk factors (T4-stage, R1/R2 resection, intraoperative tumor perforation) were present, postoperative irradiation was performed after CT-planning. Total postoperative doses of 41.4 Gy (preoperative irradiation) or 59.8 Gy (surgery only) were applied with doses per fraction of 1.8 to 2.0 Gy. Local control, survival, and pattern of side effects were analyzed at 5 years after conclusion of the trial. The frequency of local recurrence was markedly reduced by preoperative irradiation of R0-resected patients (24% vs 13%, p = 0.08). The time to recurrence was delayed (1.9 vs 3 years). The 5-year actuarial survival rate was significantly higher in the preoperatively irradiated group compared to the not pre-irradiated group (40% vs 28%, p = 0.027). Multivariate analysis revealed UICC-grading as the only independent parameter for local control (p = 0.0003), while preoperative irradiation (p = 0.07) and T-stage (p = 0.08) only displayed a trend. For patient survival, age (p = 0.0003). R-status (p = 0.01) and UICC-score (p = 0.001) were significant prognostic factors. Preoperative irradiation had a non-significant effect only (p = 0.078). Radiation-induced side effects with a LENT-SOMA score > 2 were observed neither during frequent follow-up nor at an additional examination of those patients still alive in 1998 (n = 25). Of 4 pre- and postoperatively irradiated patients with risk factors, 3 had side effects grade 1 or 2, predominantly rectal changes, at 5 to 11 years after treatment. A positive effect on tumor control and survival is achieved with preoperative irradiation with the doses used in this study, with moderate side effects.