Long term follow up shows chemotherapy after radiotherapy does not improve survival for patients with rectal cancer
Appearing in Lancet Oncology, long term results of EORTC trial 22921 with 10.4 years median follow-up show that 5-FU (fluorouracil) based adjuvant chemotherapy after preoperative (chemo)-radiotherapy for patients with cT3-resectable T4 M0 rectal cancer does not improve survival or disease-free survival.
EORTC trial 22921 explored the value of adding chemotherapy to preoperative radiotherapy either concurrently, or as an adjuvant, or both for patients with cT3-resectable T4 M0 rectal cancer. Between April 1993 and March 2003, 1011 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.
Prof. Jean-François Bosset of the CHRU de Besancon - Hopital Jean Minjoz in France and lead author of this study says, “When we looked at the results after five 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 four for overall survival and from year two for disease-free survival. 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 time frame. The 10-year overall survival rates were 51.8% (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 (HR=0.91, 95% CI 0.77-1.09, p=0.32). The 10-year disease free survival rates were 47.0% (CI 42.2-51.6%) for the patients receiving adjuvant chemotherapy and 43.7% (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 five years, and at ten years local relapse rates were 22.4% (CI 17.1-27.6) with radiotherapy alone, 11.8% (7.8-15.8%) with neoadjuvant radiotherapy-chemotherapy, 14.5% (10.1-18.9%) with radiotherapy and adjuvant chemotherapy, and 11.7% (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).
EORTC trial 22921 was coordinated by the EORTC Radiation Oncology Group and was conducted in 35 sites located in ten countries: Belgium, France, Germany, Israel, Poland, Serbia, Spain, Switzerland, The Netherlands, and Turkey. This trial was supported by the EORTC, grants 2U10-CA11488-21 through 5U10-CA11488-35 from the United States National Cancer Institute, Programme Hospitalier de Recherche Clinique (PHRC 1992-France), and the Ligue contre le Cancer Comité du Doubs.
John Bean, PhD
EORTC, Medical Science Writer