Total neoadjuvant treatment without surgery for locally advanced rectal cancer
Dr Alessio Amatu - Niguarda Cancer Center, Milan, Italy
I’m proud today to speak about our study that is the NO-CUT trial, an academic trial of non-operative management after total neoadjuvant treatment in locally advanced rectal cancer proficient with mismatch repair.
What was your study design?
The study is a single arm phase II trial with the aim to demonstrate that avoiding surgery did not jeopardise the distant relapse free survival in patients following their clinical complete response after total neoadjuvant treatment.
What were the results?
The first results to show that one out of four patients reached a clinical complete response and the distant relapse free survival of this group of patients is very high, it’s 97% at 30 months, and this is well above the predefined boundary of clinical meaningful survival that we posed in the trial design.
What sort of toxicities were found?
About safety we can say that we had a toxicity in line with the previously reported literature. The total neoadjuvant treatment we used is CAPOX for four cycles followed by five weeks of long-term chemoradiotherapy. Expected toxicity was in line with literature. We had only one toxic death and all reported deaths were mainly due to tumour progression in patients not responding to treatment.
An important question of the trial was the translational questions and we found that some biomarkers like circulating tumour DNA can predict clinical complete response and worse distant relapse free survival along with transcriptomic analysis that was carried out on the tissue biopsy before total neoadjuvant treatment. The predictive power of liquid biopsy was assessed on the blood samples taken after the end of total neoadjuvant treatment.
What are the next steps?
The next steps will be surely do a lot more efforts to integrate these biomarkers into a clinical algorithm in order to better select patient candidates for organ preservation strategy.
What are your hopes for the clinical impact?
I hope that we will be be able to not only identify better people benefitting from this treatment but also to improve the treatment in order to improve the organ preservation rate in our patients.
Is there anything you would like to add?
Yes, this was a very difficult study to conduct because we started in 2018 and we went through the COVID pandemic. So it was a huge effort from four academic institutions and these difficulties make our results more important.
