(ChemotherapyAdvisor) – While a persisting significant improvement exists for preoperative vs. postoperative chemoradiotherapy for locally advanced rectal cancer, no effect on overall survival was observed at a median follow up of 11 years, according to a study in the Journal of Clinical Oncology online April 23.
After first results of the CAO/ARO/AIO-94 (Working Group of Surgical Oncology/Working Group of Radiation Oncology/Working Group of Medical Oncology of the Germany Cancer Society) trial was published in 2004 that showed an improved local control rate with preoperative chemoradiotherapy, this regimen was established as standard treatment for locally advanced rectal cancer, the investigators noted. “However, after a median follow-up of 46 months, no survival benefit could be shown. Here, we report long-term results with a median follow-up of 134 months.”
The Phase 3 trial randomly assigned 799 eligible patients with stage 2 to 3 rectal cancer to preoperative (n=404) or postoperative (n=395) chemoradiotherapy with fluorouracil. Total mesorectal excision surgery was scheduled to occur 4 to 6 weeks after completion of postoperative chemoradiotherapy. Adjuvant fluorouracil chemotherapy was initiated 4 weeks after surgery or after completion of postoperative chemoradiotherapy.
At 10 years, overall survival was 59.6% in the preoperative arm and 59.9% in the postoperative arm (P=0.85). The 10-year cumulative incidence of local relapse was 7.1% in the preoperative arm and 10.1% in the postoperative arm (P=0.48). The 10-year cumulative incidence of distant metastases was 29.8% in the preoperative arm and 29.6% in the postoperative arm (P=0.90), and no significant differences were detected for disease-free survival.
“Evidently, any improvement in overall survival rates will require better control of systemic disease,” they wrote. “Integrating more effective systemic therapy into multimodal therapy has been the challenge.”
Recently, their group completed accrual of more than 1,250 patients into a Phase 3 trial, with random assignments to either the best arm of this trial—fluorouracil-based preoperative chemoradiotherapy, surgery, and 4 cycles of postoperative fluorouracil chemotherapy—or to the investigational arm, which incorporated oxaliplatin into both preoperative chemoradiotherapy and postoperative chemotherapy. Initial findings suggest oxaliplatin has increased rates of pathologic complete response; results based on the primary end point, disease free survival, will be available late 2013.
An accompanying editorial noted that “…the success of the German investigators to complete the trial, and now to provide confirmatory long term follow up data, demonstrates that such trials can be completed and that the results can be paradigm changing.”