RESUMEN
PURPOSE: A prospective study was designed to randomize locally advanced rectal carcinoma patients between either preoperative radiotherapy (+/- postoperative chemotherapy) or postoperative adjuvant chemoradiation. Two end points were evaluated, local recurrence and survival, aiming at defining prognostic parameters that can help in the choice of the optimum treatment modality. PATIENTS AND METHODS: This is a prospective randomized clinical study including patients with locally advanced low rectal cancer treated at the National Cancer Institute (NCI), Cairo University, during the period from December 1994 to January 1999. Fifty patients with previously untreated rectal cancer were randomized into two groups, Group I: Subjected to surgery followed by radiation therapy (50Gy/5 weeks, 2Gy/fraction, 5 days/week) plus chemotherapy and Group II, subjected to preoperative radiotherapy (46Gy/4.5 weeks, 2Gy/ fraction, 5 days/week) followed by surgery +/- postoperative chemotherapy. Chemotherapy in the concomitant setting was given in the form of Leucovorin in a dose of 300mg/m2 as a short i.v. infusion followed by 5-FU in a dose of 350mg/m2 as a 6 hour i.v. infusion, whereas adjuvant chemotherapy consisted of 5- FU as 600mg/m2 short i.v. infusion weekly for 48 weeks, in addition to levamisole tablets. RESULTS: The long-term treatment end results obtained showed that group I patients had a slightly higher 10-year overall survival (OS) rate when compared to group II patients (63% versus 60%, p=0.698). The corresponding figures for the 10-year disease-free survival (DFS) were 65% and 66%, respectively, p=0.816. Although the 10- year local failure rate (persistent/relapsed disease) was higher for the preoperative group, it was not of statistical significance, (30% Vs. 8%, p=0.057). On the other hand, the 10-year distant metastasis free survival was higher in the preoperative group (88% Vs. 72%), yet this difference did not reach statistical significance (p=0.16). The rate of acute radiation reactions was higher in the postoperative group, with no increase in the operative complications in the preoperative group. Moreover, none of the 50 patients had grade 3 or more late radiation/surgical squealae. There were no grade 3 or 4 chemotherapy related toxicities. CONCLUSIONS: This work showed equal results for DFS and OS rates between preoperative and postoperative radiation therapy with the same acceptable acute and late radiation toxicity. High dose preoperative irradiation did not cause any significant increase in acute or late radiation induced reactions, delay in wound healing or increased postoperative morbidity when compared to postoperative adjuvant radiochemotherapy. Duke' s stage and response to preoperative irradiation proved to be of significance regarding DFS, while compliance to systemic therapy was of significance regarding both OS and DFS.