Neoadjuvant Chemotherapy in the Treatment of Locally Advanced Rectal Cancer: New Points of View

Treatment of locally advanced rectal cancer rises to main questions regarding loco regional control and induced morbidity. Future therapeutics options will still obtain a better control of metastatic outcome, observed in 30% of the patients without jeopardizing functional results, nor increasing the rate of post-operative complications. In order to optimize the different therapeutic options, GRECCAR4 study has evaluated the contribution of MRI to select patients amenable to a new strategy and for evaluating the tumoral response to pre-operative intensifyied treatment. Induction chemotherapy is aiming to improve the tolerance and the compliance to the medical treatment as compared with the adjuvant setting. In GRECCAR 4, the FOLFIRINOX protocol was delivered before centralized evaluations with MRI of the tumoral response aiming to intensify radiation therapy for non-responders (testing 50 to 60 Gy in two arms) compared to the standard dose delivered for a good responders. Preliminary evaluations for 197 patients in October 2014 demonstrated that the tolerance to FOLFIRINOX is satisfactory. The tolerance of combined modality treatment with chemo-radiation receiving 60 Gy as compared with patients receiving 50 Gy is not different. A definitive analysis of long term results, in term of local control and impact on the metastatic disease is warranted to validate these approaches for locally advanced rectal cancers.