Chemotherapy after radiation does not improve survival of rectal cancer
Long-term results of European Organisation and Treatment of Cancer (EORTC) trial 22921 with 10.4 years median follow-up show that 5- fluorouracil (FU)-based adjuvant chemotherapy after preoperative chemoradiotherapy for patients with cT3-resectable T4 M0 rectal cancer does not improve survival or disease-free survival. These results were published in Lancet Oncology (2014; 15:184-190).
EORTC trial 22921 explored the value of adding chemotherapy to preoperative radiotherapy either concurrently, as an adjuvant, or both concurrently and adjuvantly for patients with cT3-resectable T4 M0 rectal cancer. Between April 1993 and March 2003, 1,011 patients were randomized to four treatment arms: 252 patients received preoperative radiotherapy alone, 253 patients received preoperative radiotherapy-chemotherapy, 253 patients received preoperative radiotherapy followed by adjuvant chemotherapy, and 253 patients received preoperative radiotherapy and chemotherapy followed by adjuvant chemotherapy.
“When we looked at the results after 5 years' median follow-up, we saw that chemotherapy, regardless of when it was administered, significantly improved local control. However, adjuvant chemotherapy did not improve survival or disease-free survival, but we noted that the curves by adjuvant treatment did diverge progressively starting from year 4 for overall survival and from year 2 for disease-free survival, said lead author Jean-François Bosset, MD, of the Centre Hospitalier Régional Universitaire de Besançon - Hôpital Jean Minjoz in Besançon, France. “This suggested a possible delayed benefit, and we wanted to resolve this. The long-term follow-up results suggest that new treatment strategies incorporating neoadjuvant chemotherapy are required, because adjuvant chemotherapy does not demonstrate any significant long-term benefit on overall survival or disease-free survival.”
Results of EORTC trial 22921 show that compliance with adjuvant chemotherapy was poor, and only 42.9% of the patients received the planned dose within the scheduled timeframe. The 10-year overall survival rates were 51.8% (95% confidence interval [CI], 47.0-56.4) for the patients receiving adjuvant chemotherapy and 48.4% (95% CI, 43.6-53.0) for those in the surveillance groups (hazard ratio [HR]=0.91, 95% CI, 0.77-1.09, P=0.32). The 10-year disease-free survival rates were 47.0% (95% CI, 42.2-51.6) for the patients receiving adjuvant chemotherapy and 43.7% (95% CI, 39.1-48.2) for those in the surveillance groups (HR=0.91, 95% CI, 0.77-1.08, P=0.29).
Most relapses occur within 5 years. At 10 years, local relapse rates were 22.4% (95% CI, 17.1-27.6) with radiotherapy alone, 11.8% (95% CI, 7.8-15.8) with neoadjuvant radiotherapy-chemotherapy, 14.5% (95% CI, 10.1-18.9) with radiotherapy and adjuvant chemotherapy, and 11.7% (95% CI, 7.7-15.6) with both adjuvant and neoadjuvant chemotherapy (P=0.0017).
There was no difference in cumulative incidence of distant metastases (P=0.52). The frequency of long-term side effects did not differ between the four groups (P=0.22).