Author Response To: Total Neoadjuvant Therapy in Rectal Cancer—improvement or Overtreatment?

Editor We thank Mroczkowski and Dziki for their interest1. Stage II does include locally advanced T4 tumours, arguably the ones that should have neoadjuvant therapy. The data lack the enrichment required for subgroup analysis and to try would be to sink in retrospective quicksand. Potential oncological improvement should be balanced against the risks of drug toxicity, unnecessary treatment of low-risk tumours, and disease progression while on chemotherapy. The interval to surgery in the included studies was relatively short and it is conceivable that complete pathologic response rates would increase with a longer interval. This approach provides an opportunity to assess the inherent biological profile of the tumour with the potential of facilitating a more selective practice of surgery. However, whether TNT translates into reduced disease recurrence and improved disease-related survival, or increases the proportion of patients suitable for non-operative management remains unclear. In the absence of a definitive oncological advantage, we cannot advocate that TNT should be undertaken in all patients with locally advanced rectal cancer. However, in view of the potential benefits demonstrated, including improved chemotherapy compliance and superior pathological response, this approach merits further evaluation2. RCTs, in particular amongst patients with high-risk disease, would be welcomed. Selective risk-adapted strategies based on tumoral imaging and biology, in combination with neoadjuvant therapy tailored to its molecular signature, represents an attractive step in rectal cancer management. A. Zaborowski , A. Stakelum and D. C. Winter Centre for Colorectal Disease, St Vincent’s University Hospital, Dublin, Ireland