Brændengen M et al. (2008) Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol 26: 3687–3694

Approximately 10–15% of primary rectal cancers are nonresectable, although preoperative radiotherapy can shrink these tumors and permit subsequent radical surgery to be performed. The randomized study by Brændengen and colleagues investigated whether the addition of chemotherapy to preoperative radiotherapy could improve downstaging, survival and recurrence rates in patients with nonresectable rectal cancer.

In total, 207 patients (aged <75 years) with primary, nonresectable or locally recurrent adenocarcinoma were randomly assigned to receive 50 Gy radiotherapy alone (n = 109) or 5-fluorouracil concurrent with 50 Gy radiotherapy, followed by leucovorin (n = 98). Surgery was performed 5–8 weeks after the last radiation treatment.

At follow-up (median 61 months in survivors), 63% of patients who received combined therapy were treatment-failure-free compared with 44% in the radiotherapy group (P = 0.003). Cancer-specific survival at 5 years was significantly higher in the combination-therapy group (72% versus 55%, P = 0.02). A trend towards improved overall survival in patients who received both therapies was evident, but the difference between the groups was not significant (66% versus 53%, P = 0.09). Local control rates were also higher in the combination-therapy group. Grade 1 and 2 diarrhea was the most frequent acute toxicity. Patients who received combination therapy experienced significantly more grade 3 or 4 toxicity than those given radiotherapy alone (28% versus 6%, P = 0.001).

The authors conclude that preoperative chemoradiotherapy is well-tolerated, improves local control, time-to-treatment failure and cancer-specific survival compared with radiotherapy alone in patients with nonresectable rectal cancer.