At the request of the National Thesaurus of Gastrointestinal Cancer (TNCD), the SOR program undertaken by the French federation of cancer centers and now led by the French National Cancer Institute, completed a systematic review to evaluate the value of perioperative chemotherapy in the management of resectable rectal adenocarcinoma in collaboration with clinician experts.
Methods: Results of a systematic literature search using Medline and Embase (from January 1996 to October 2007) were completed by a survey of Evidence- Based Medicine websites. All phase III randomized trials and systematic reviews comparing surgery (alone or associated with adjuvant therapy) to the same treatment plus chemotherapy, or comparing different perioperative chemotherapy modalities in patients with resectable rectal adenocarcinoma, were included in the study. The quality and clinical relevance of the trials were evaluated using validated checklists, allowing to associate each result with its level of evidence. Data synthesis was performed taking into account both efficacy and toxicity outcomes for each intervention. Finally, research recommendations were formulated.
Results: Of 29 studies meeting the selection criteria, 19 were included after critical methodological and clinical appraisal. As compared with preoperative radiotherapy, preoperative chemoradiotherapy with 5-fluorouracil and folinic acid does not improve overall or relapse-free survivals but decreases local recurrence rates. Postoperative chemotherapy with 5-fluorouracil and folinic acid does not improve overall or relapse-free survivals, whether the patients received preoperative radiotherapy or preoperative chemoradiotherapy, whereas it seems to decrease local recurrence rates after preoperative radiotherapy but not after preoperative chemoradiotherapy. As compared with postoperative chemoradiotherapy, preoperative chemoradiotherapy with continuous infusion of 5-fluorouracil does not improve overall or relapse-free survivals, but decreases local recurrence rates as well as acute and long-term toxicities. In the absence of preoperative radiotherapy, fluoropyrimidine-based postoperative chemotherapy improves both overall and relapse-free survivals and decreases local recurrence rates.
Conclusions: Preoperative chemoradiotherapy reduces the risk of local recurrence as compared with preoperative radiotherapy or postoperative chemoradiotherapy.