Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial

SPS commentary:

According to an accompanying commentary, the pace of change in rectal cancer treatment has accelerated. In the past 5 years, a watch-and-wait strategy in patients with complete clinical response after radiotherapy has been accepted by many as a breakthrough, and currently it is believed by some experts that the total neoadjuvant treatment era has begun as supported by the findings of this study. It notes that disease-free survival benefit does not always translate into an improvement in overall survival, shown by a meta-analysis of randomised trials exploring adjuvant chemotherapy versus observation in stage II colon cancer; one of the reasons being longer survival following recurrence in the observation group than in the chemotherapy group. This might also be the case for rectal cancer. It alludes to two other trials of neoadjuvant or adjuvant chemotherapy or the addition of chemotherapy to neoadjuvant radiotherapy in rectal cancer where disease free survival benefit also did not translate into a long-term improvement in overall survival. It adds however, that as preliminary results of the phase 2 OPRA trial showed that about 50% of patients had organ preservation 3 years after total neoadjuvant treatment by using a watch-and-wait strategy, confirmation of this finding by a phase 3 trial would provide robust evidence favouring total neoadjuvant treatment, even without the benefit in overall survival, because the avoidance of surgery leads to a meaningful improvement in quality of life.